Sc.otn Fernando Valley ;;tate College
S'I'UDIES IN 'l'fiE SYN'rHESIS OF' POLYCYCI,IC COYIPOUNDS
II
A thesis s1fumitted i.n partial satisfaction of the
requirernents; for t:-.he degree of J:llr.ste:c of Scienc:e in
Chemistr:y
by
Walter Bruce Avila
I'
I
1._
L••
·-----··---·-->·-
'
The thesis of Walter Bruce Avila is
approved~
San Fernando Valley State College
June, 1971
'
·-~--" -~ ~-
-- ·-·--" ---·
~--· ~-
-· .. -,_.,
-~--- -···-~-~-·-
_,_.- -·-
l. J..
,.
----- --------- - ... ------- ---- -- ------ --------- ---------- -- ---· ---- -· - -- -- --- - - - ---- ---
1
I
l
To my parents
who made this possible
and worthltlhile
iii.
r ,...-.. . . . . . . . . -··-··---.. . . . . .
i
·~···
~---
-~
~-·-···
..·-··---····--·-.. . . . ___________ ............ . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . ·-.........
f
\
J.;.CKNOWLEDGMENT
I am deeply· indebted to Dr,. Ricardo A. Silva., for his . ~
!help and guidance throughout this projecto
I am especially
fgrateful for the opportunity of studying and learni.ng about
II nucle-""r
.......
magnetic resonance from Dr. Silva and, most of all,
I
'
lfor his friendship and enthusiasm for art in organic
[
!synthesis.
I
.
I am also appreciative to Dr. Carl Olsen, for his
I
generous gift of special reagents w·hich I used in the
dehydrobrornination reactions, and to Dr. Francis Harris
I for
his stimulating d:i.scu.ssions and ideas concerning
l syntJwtic teclu:iqu.es.
ICommittee for
Finally, I am indebted to rny Thesis
their many constructive crit.icisma.
I
I
!_ C'">•-·~-~0' ·~--~---~-----~---·~·~-·---·--------·-><·•-------··~~-----·- .
-·-·••OoOOoO
----~---
•••••- •
- - - - ' ' ' • • __ ,,,,., - - - ' ' '
iv
•-'~•'''••••'•-·••••>
---
'0''0o'-••• ' ' ' ' ' '
••••-••'·-·
•''-•'''--
TABLE OF CON'I'ENTS
Paae
__
-~-=>
LIS 'I' OF FIGUB.ES.
•
•
&
TAB I.E OF ABBREVIATIONS
ABS'rRF:..CT
~
e
CHAP'l'ER II.
CRAPTER III.
.
~
• •
CHAPTER I.
.
~
•
vi
• •
~
0
• •
0
viii
•
INTRODUCTION
•
SYNTHETIC SCHEME.
vii
•
•
"
• •
•
1
• •
•
8
DISCUSSION OF RESUL'rS. • •
•
18
•
1.8
Diels-Alder Reactions of 2, 3-D:i.Inethyl-1, 3-
butadiene.
•
• • •
•
•
Photochemical Cycloadditions.
Bromin.ation Reactions
•
•
&
Reactions of Photoadduct ( 5) •
•
Dehydrobromination Reactions. •
CHAP'l'ER
v.
PROTON
:r.";.:"~GNETIC
•
•
23
•
26
28
30
•
32
RESON.l'J.-.JCE SPECTRA
•
•
4:6
•
•
~
Procedures.
BIBLIOGEAPHY
0
•
0
EXPERI~1EN'rAL
GEmeral
..
•
Miscellaneous Reactions
CHl'.P'rER IV.
19
•
•
47
•
•
v
~
46
~
56
,... --
-~
I'
i
LIST OF FIGURES
Fiaure.
'!~--·-·
~
-1
4 ,5-Dimet.hy1-3 ,6-dihydrophthalic
Anhydride.
~
5
• • • • • • •
••
&
•
•
~
•
0
2
Dimf~·thy1·-4,
3
3,4,8,9-Tetramethylbicyc1o[4.4.0]deca-3,8diene-1,9-dioic Anhydride • • • • • • • • •
3 9
31 4 /.. 8 1 9·-'l,etramethy 1 tetracyClO ( 4 o 4 ~ Q Q I
o4 I I:S] decane-1, 6-dioic Anhydride. • • • • • •
36
1, 6-Bis (hydroxymethyl) -3,4, 8,9-·tet:ramethyltetracyc1o[4.4.0.o3,9.o4,8]decane. ~ • • • •
37
3 9
3l4 8, 9-'retramethyltetracyclo [4. 4. o. o t
o4,S]decane-1;6-dicarboxylic Acid~ • • •
38
4
5-dimethyl-3, 6 ·~dihydrophthalate •
33
34
35
0
5
6
..
3, 4, 8,9·-'I'etrabromo-3, 4, 8, 9~tetramethyl~
bi.cyclo [ 4 ~ 4 ~ 0] -decane-·1, 6-clioic Anhydride;
J. 3b • e s • • • • a '
e
•
•
•
o
•
7
t:1
•
"
..
•
3, 4 1 8 1 9-•retrabromo-3, 4, 8 f 9-t:etrarnethylAnhydride;
1. 3a. .. ,
.o
.-.
•
8
bicyclo[4~4.0]-decane-1,6-dioic
8
"
•
Bromolactone 15.
9
•
•
...•
•
•
•
•
•
•
..
•
•
•
e
~
~
Photolactone 27 • • • • • •
12
1, 6-~Bis (br:omomethyl) ··3, 4 f 8,9-tetramethylbicyclo[4.4.0]-deca-3,B-diene-l,6-dioic
Anhyd:r:.ido
Q
13
·-·
..
•
•
•
•
•
•
Photodi.bro:mide 6b. • •
··-···
-~--~---···-·
w
.----~--~-~---··-"
vi
•
•
•
•
•
•
. ......
~
•
40
41
42
43
11
~.---·-
~
1, 6-Bis (hydroxymethyl) -3 1 4,8, 9-tetramet:hylbicyclo[4.4.0]deca-3,8-diene • • •
• •
10
'- .....
•
44
45
TABLE OF ABBREVIATIONS
ADA
acetylenedicarboxylic acid
DBN
1,5-diazabicyclo[3.4.0]nonene-5
DNAD
dimethyl acetylenedicarboxylate
DMB
2,3-dirnethyl-1,3-butadiene
D.MF
dimethylformamide
DMSO
dimethyl sulfoxide
HI'iPA
hexamethylphoramide
LAH
lithium aluminum hydride
THF
tetrahydrofuran
vii
A..BSTRAC'l'
STUDIES IN THE SYNTHESIS Ol? POI,YCYCJ... IC COMPOUNDS
by
Walter Bruce Avila
I
Master of Science in Chemistry
June, 1971
I
l
I
Diels-A1der (iddi tion of acetylenedica:eboxylic acid and
'its dimethyl ester to 2,3-dimethyl-1 1 3-butadiene {DMB) gave'
11:1 adducts.
Only the former reacted further to give a 1:2
adduct {as anhydride).
This bicyclic 1:2 compound
under~
jgoes an intramolecular photosensitized cycloaddition to
I
igive the tetracyclic anhydride which, in turn, was con~
I
I
lverted to the corresponding dio1.
The diol was treated
!
\with phosphorus tribromide and phosphorus pentabromide; the
jexpected dibromide could not be identified conclusively as
I
'the product and the Wurtz reaction with it failed to yield
any ring closure product.
Iconverb~d
Iyielded a
The tetracyclic anhydride \vas
to t.he diacid, vlhich on anodic decarboxylation
tetracyclic four membered lactone rather t.han the
!alkene.
I
I
'rhe 1:2 adduct was brominated under t'>,;o different con-·
I di tions
I
to yield in pure form t\vo isomeric tet.rabromo com~
I pounds, both of 'IA•hich failed ·on dehydrobromination to yield
1
i
v·iii
r·~-·-·-··-~-
. .-.. . . .
-~-- ~-.- ~~-···~~~----~· ~-----c·~--·--·-···~··-----~---·----·-··--~<0-·~----~
..
---~~.;----·-·-··-·~ ---~---·.-·><·
..
~--·~·-··---
······---
0•4 - · - · · - · " . . . .
-
-~-
. -. . . . .
~·-~
. . . . . ._ _ _ _
'-~--
••
!the endocyclic double diene~ Spectral evidence su9gests
I
I that the dehydrob:t:'omina ted product may be some mixture of
I
jthe isomeric tetraenese
II
Physica.i constants were obtained for
Isynthesized and identified in this "V!Ork •
.; ,..,.
v
.....
all compounds
INTRODUCTION
There are numerous publications in the literature on
the synthesis of strained polycyclic ring systems~ 1
The
synthetic challenge represented by these systems led inves.tigators to make organic synthesis an art and forced them
!
lito develop ingenious methods for obtaining a host of appar.
2 3 4 5
!ently anomalous polycycl1c systems. '
'
'
Some of these
!have unusual structures shaped in the form of boxes, cages,,
lor propellers and have led to the coinage of terms such as
I
I "Box Dimers, 116
11
Cage" compounds, 7 or "Propellanes".
8
In-
terest in these compounds has been prompted in part by
!their unusual and novel molecular structures.
Theoret-
lically, they are intriguing because of abnormal bond
I!angles,
bond orders, and unusual spectroscopic properties.
I
j Additionally these molecular systems are interestin~r
j
!because of the possibility that they may possess extraor1
]dinary biological activity. 9 'lO,ll
l employed
This activity might be
in various ar.eas ranging from the development of
I
!more efficient ~esticides to new and more effective drugs.'
i
j However, if studies are to be made on these systems, they
l
j must first be easily available in sufficient quantity.
l synthetic
rrhe
schemes which have been developed so far have
'
L_ ~ -·· ---- -------- -- ----- -- --- ·-····-- ------- --- -----------· ---- .. ---·-··- -·-· ----- ---- -..... ·-- -------·----- --· ·1
f~~"--"~=· ·~~ .. .-~~ ~--~-·••~·~----.--._.______ -'----~-- ~·~---·~~ ~• -··••••·-~-·~ -~--~--=~·~-----
nw
-•·-·~---·~--~•<•~~0·~·---··--~·- -••·•~--,,
••- ~- •;-·~·- •--·•~•• -· , -·-
~·
·-•••"-'
/ indeed been ingenious but. have often involved several steps'
i
lwi th a subsequent reduction in overall yield.
I
!of
The purpos(::!
this reseai·ch was to study the synthesis of certain
i
jpolycyclic systems and to develop methods for obtaining
!them in high overall yields.
I
i
.: on
3 9
the tetracyclo [ 4. 4. 0. 0 '
1
j there
/
IivJas
!
Special emphasis was placed
4 8
~ 0 ' · ] decane system for which
. 10 12
\vere only a few knovm syntheses.
'
The synthesis of certain cage t.ype polycyclic systems
made possible by 0. Diels and K. Alder \tlho, in 1928,
!
!provided a major synthetic bre.akthrough. In 'tr17 hat ha.s
i
!become a classic paper, 30 Diels and Alder presented one of
l the
most useful reactions in organic chemistry, the
cycloaddition of a diene with a dienophile.
Iknown
1,4~
This reaction,
as the Dieh>-Alder reaction after its discoverers,
I
lwas considered to be of such value for the synthesis of
I
!cyclic compounds that it won Diels and Alder the Nobel
I
!Prize in chemistry in 1951.
The major advantages of the Diels-Alder reaction are
I that
it proceeds cleanly to give extremely high yields of
product and it is sterospecific.
The diene reacts in a cis
' conformation to give products in which the stereochemistry
of both diene and dienoph.ile are retained. 31
By the appro-
I priate choice of initial reactants, it is possible to
I
Iobtain a wide
variety of compounds from the Diels-Alder r:e-
' act:.ton
.
This multi t.ude of produc·ts is limited only by the
fact 31 that: the dienophile must be substituted with elec-
1
q
I
1
.
-·~~~-~----·-·---~~······
-- . -~~-- -----------~------- ----~~-----··--~~..~-·-·····- ~-----·--·-----·-··------ ------··--·---~~-~---·-·---~-~-- . .-. ------~-- ..- ·------------- ... -- --------~ ---
..
---"
-----------------------------·-----·--c--- -·-··-. ------------1
1tron vd.thdra;;·.:in9 groups such
~~--~--------
'-~--'-'"
--------~---------
!
--~-_,
______ ----------------------------- -- ------ ···- --- -----
as
-co 2 H
or -C=:N.
The nature
lof the cyclic materials obtained from the Diels-Alder re-
i
!action and the ability of these products
to
undergo ring
1
!closure to cage type compounds is a function of the struc1
1tu:ce
of the diene and the dienophile.
i
l.
!1t
For these reasons
was felt that the materials for entry into the poly-
lcyclic systems to be studied in this work could best be
I
j obtained
by a. Diels-Alder reaction involving a suitable
!acetylenic dienophile A with a diene of type B.
l
X
X
I
lII
I
X
B
oc:
c
A
j
]
X
D
X - electron withdrawing group
I! The
initial product C could then undergo an a.dditional
l Diels-ll.lder reaction vd th
I
a second molecule of diene to
give the desired material D.
I action.
This double Diels-Alder re-
is not 'di thout precedence in the literat.ure and was
I obsen:ved as early as 19 38, by Alder and Backendorf. 14 Com-!
Ipounc1 D should thus be obtainable in high yield and suit!
! able for conversion into numerous polycyclic systems.
II a.bly
Intramolecular phoi:osensi tized cycloaddi tion of suit·oriented double bonds is a photochemically allowed
! process
I
-
and rules governing such reactions have been
pos-tl.a.ated.
32
Compound D contains double bonds which may
r-~•"0··~-.,
-0•0
~~-·~-,~~~-~·~·~··~·~--·~-~·~·_, . . ,.~~-~~~-~~···~·~·-·-~--- . .~- -~-~-~~··---~~·~• ~~~ -~
'••'
•••-~''-
•'--'
···~-----·~···--• ~W$ --·-···--~-••• ----~.·~··-••
••-
•-•-••
•
J
lbe sui t~ably oriented and would be expected· to give sys!
;
)3
Items· such as E or irradiation in the presence of a phot.o-
I!' SEmsi ti zer
e
I
!
X
l
f
X
·;
i
l
l
l
!
...
i
.w
I
!I 'l:his
photosensitized cycloaddi tion process depends on
i
l several
fundamental concepts~ The first is that for 'che
.
absorption of light, elec·trordc transitions which involve
I
Il
!changes
in mul t:ipliei ty are forbidden.
Most organic mole-
lcules have singlet ground states (all electrons paired) and
I
.
II states
(called intersystem crossing) leads to a triplet
1absorpt1on of ultraviolet light results irt singlet-singlet
l
I'
•
•
lelectron1c trans1tions. Inversion of spin in these excited
I energy
~ zation
state v1hich t.hen reacts to give products.
Sensiti-
of this reaction involves triplet energy-transfer,
I
I and compounds vrhich are unable to absorb light at long
I
wavelengths
!'l'his
l
ma.y
t.hen be sensit.ized by additives which do.
means that compounds whose upper singlet and triplet
states are widely separat.ed, thereby making intersystem
I
I crossing
difficult, may bt~ excited to the triplet st.ate by
!
j a sensitizer.
I agent
This sensitizer acts as an energy transfer
and supplies the energy necessary to effect the
l
. !l change from a singlet to a triplet state.
~~ -r·•·-•-•<-- , ·-· -- •••·•~ •'--·-~•--<- --·" -~ ·-·-~•-•-• •• • ···-•~ • ~ ---· -·~-.- ...-- _. ..•~.--.$•••-•-··-.,-
·- •
The activated
r··. ----··-·---............... --.. . .............. ·-· ............... ---·---·--------··· ......-............ ---·····--.. -- ................ -· .................. ··-... -- ..................... ------ ............. .
!
!compound then reacts to give products, in this case the
t
!polycyclic compound E.
Il
'1,
Compounds such as D may also be used to study
(
I
32
2 + 2 + 2 + · 2 ) cyc_oa
] dd 1' t 1on
'
.
reac t 1ons.
Th
' t.·ype o f
.1s
lcycloaddition involves two isolated double bonds reacting
1
.
lwith a photochemically excited acetylenic compound and giv-·
)
ling rise to two products, one resulting from "parallel"
)additi?n and one resulting from "perpendicular" addition of·
!the acetylenic compound.
!
!
These modes of addition are
sho~m
In each case only the reacting bonds are shov-m.
jbelow.
l
X
X
I
II
I
+
Ill +~I
· hv ?;?
I
X
dJ
1 .
X
+x---x+jj
IAt
least
Parallel Addition
Perpendicular
Addition
two
reactions involving perpendicular addition
have been noted in the literature. 21
The use of a double diene of structural type
F'
~.,
r··-··-·----····· ···--···--·-··-·--·--···-· .. ·-----·-·--·-·------·--············-·----··-------·-·- .... ···------·------------ ··-··--···--·-..--.. -·---···· ..............
I
.
iwill also permit the study. of the analogous parallel and
!
l
/perpendicular thermal addi t.ions to dienes by acetylenic
I
'
jcompounds.
i
t
These reactions would be expected to give the
.
!following
results.
I
.
.
I
X
I
I
X
~I
~+Ill
Parallel
l
X
X
I
I
I
I(
!
~~
+
X--
-x
+
0-b
~­
,~
. Perpendicular
I
!
I
!Again, only the reacting portions of the molecules are
II shmm.
'rhermal additions to similar systems have preI1 VJ.ous
.
1y b een o b serve d • 23.
I
i
The final area of interest involves the synthesis and
l!,study of strained polycyclic
a1kenes as, for example,
I struc·'cure G.
I
I
G
I
! Strained alkenes of this type may be expected to have
I
!.rather peculiar chemical properties because of their
I
I
I
,,, ••------·-•
••
{._..~,.. -~·•
•o-••
"'"••--•~·---.~·••·•~·--~--~V•~·~•·-•-·•-" ,,~·- >'~--- -~~-·~"---"•~---·-- --···~··•-•··------·--·•••••~
·-·~·~--
·-~···•••- ~•·'··--·•-•
•>->•-···-·~O·•- ~· ~.
unu~
• --•~• • ..
•o••·
•
•,
r·
··~·-n
..........
~.·~····--
--
--·~----·
~··
·-.. . . . . . .
·~ ·-~~-~--·-···~-
·-·--····---·---··-·
--·~·~·.
··-
-~-~~~----··"'"""-·<•---·-·-··--
'I
These l)roperties might be
!sual strained structure.
l
'jpected
to result from
!
~simply geometric.
I
ex~·
The first of these is
2
Normal alkenes are sp hybridized and
t'vvo
factors.
.
!all six atoms of the alkene should lie in a single plane.
lin addition the bond angles between certain of the atoms
I
!should
be approximately 120°.
I.
This is illusi.:rated belm.;.
I
!
II
!
I·
I
I
jMeasurements using models show that the bond angles of G
'
are not on the order of 120° but closer to 72° for angle a
and 90° for angle b.
1
Such deviations from "normal
11
bond
angles -vmuld be expected to lead to deviations from 'lnor-
1
1 mal"
.
b
.
chem:t.cal
ehav:t.or.
!double bond itself.
.
'rhe second factor ~nvolves
the
The double bond is oriented in such a
I
fashion that only one-half of the lobes of the pi orb'i tals
are exposed externally, the other half being more or less
!buried inside the polycyclic ring structure.
Icumstance
1
.
~vould
Such a cir-
preclude trans a.ddi tion to the double bond
!but would be extremely favorable for cis addition.
I
I intended
I study
It was
to synthesize strained alkenes of type G and to
their chemistry.
CHAPTER II
SYNTHETIC
1·
SCHEMl~
Having decided to use the Diels-P.. lder reaction to fur-
i
/nish the needed starting materials for polycyclic synthesis
Iit was
then necessary 'co decide on t.he choice of diene and
I1acety
. 1 en1c
·
i
d.1enoph.1le Ior
-·
1·
·
use 1n
t11s
react1on.
·
The s1m-
jplest diene that could be used was 1,3-butadiene.
Ithe handling
I. ex1sts
. 1n
.
11t
Iconverted to
However,
of this diene \'las complicated by the fact that
gaseous
f
orm at room temperature, and could be 1
a liquid only
at inconveniently lov1 tempera··
For this raason it was decided to use a suitable
1tures.
!derivative of 1,3-butadiene.
After considering the merits
I
!of several compounds,
I
I finally
IFirst,
chosen.
2 ,3--dimethyl-1, 3-butadiene
(m·lB) was
There vlere several reasons for this choice.
and probably most important,. was that this diene
vlaS
I
leasily obtainable in quantity.
!advantageous physical features.
In addition DHB had two
It was a liquid at room
, temperat:ure v;d.th. a boiling point. of
I
'
!that
besides being a
r~a.ctant,
68-~69°.
the diene could also serve
I
las the solvent medium for the reaction$
j physical
!' groups
feat:ur(~
This meant
The second useful
was due to the presence of t:he
attached to this diene.
met~hyl
As reactions proceeded_ from
i
Ithe
diene to unsa·turated adduct.s of type C and D and fi-
!'""'""''" ··-•··-··~·•·r •·-·-·---····---~·-
•-- ·--·•-·-·
·-·~·~--~-
---·--•··
---~·-·-•··--~---••·-·--·•-·-••···••-------··••8
••·•··-·•·-·
~·-·-
·•·•-··- •-··•·•····•··-···-•-•¥--•• ·-• '• •· --
-···~-''"'''
,,.
lnally t:o saturated ca.g-e t.ype compounds of s·tn.1ct.ure E the
J
•
i
!magnetic
environment of the methyl g:roups would change ap-
!preci.ablyo
This change would allow the reaction to be
fol~.
l
!lowed conveniently by proton magnetic resonance (pmr) spec-•
I! troscopy.
The acetylenic dienophiles chosen were ace,tylene-
1
Idicarboxylic acid (ADA) , and
I (DMAD) ~ l1.gain the choice of
dime·thyl acetylenedicarboxylate
these dienophiles was decided
upon not only because of their reactivity but because the
infrared and prnr· spectral properties of the acid and ester
I!groups
made the products easily characterizable.
1 thetic
.scheme proposed for this research using these rc~ac"·
The syn-
ltants is described below.
I
I
lbe
The Diels-Alder reaction of D!-'lB with ADA or DJ'V1A.D v10uld
expected to give adducts 1 and 29
l
E
I',
Rl-R2 ·E
"'R
I
-C0·-0-CO~
·- -co 2 crr 3
E
2
2
l
this syn·thetic scheme R -R 2 and E rornain t.he
1
!
I same. and represent the groups shovm above~ !1-ddH.:ion of a.
1 Throughout
Isecond
molecule of DMB to the above compounds should give
!
]4
jadducts 3· and 4, respectively.
I
I
I
R
X
1
E
4
!Because
of the nature of compound 2, the addition of a sec-:
l
land nolecule of diane would be expected to require fairly
i
j extreme co1~.di tions to obtain adduct 4.
I]would..
These conditions
.
be necessary because the ester group might not be a
I
Istrong
enough electron vdthdrawing group to activate the
I
!alkene double bond for addit:i.ono
1. compound
1
2 might sterically hinder the reaction by prevent-\
the stereoelectronic requirements of this reaction to
1 ing
Ibe
I
Also, the ester groups in
met. 36
-7
3
/
6a
5
6b
I
)
7a
\
7b
l
II
l... ---- ···-· ...
=
X
X ==
8
9
OH
Br
['"'"""'' "' '.,''"
..................... _, _____ ....- ........
-.~---·-----
..·---..
·-··-·----·--~
..-···--·---· ................................. ---··
......................
-· ---- .......... ..
The key reaction in our synthesis of polycyclic cage
1
Icompounds
1.vould be a photosensitized cycloaddition.
•rhis
!
!vmuld be achieved by irradiation with a mercury arc lamp
I!
•
;usJ.ng a compound such as acetone as the photosensitizer.
!
i By ana 1 ogy t o prev1.ous
'
syn·th eses, ? ' lS J.. t was expec t e d -c"'hLa t .
i
24
!photolysis of 3 would give compound 5.
Base hydrolysis
!
l of
!
the anhydride ring of 5 would yield the diacid 7a '\'7hich
jon anodic decarboxylation should give the alkene 8 •.
Anodic'
!decarboxylation
of such 1,2-diacids have been extensiVtlly
i
!
•
17
.
istudJ.ed
by several research _groups and were shown to g1.ve
I
1
:
high yields of alken(~S which '\'7ere unobtainable by other
1, me~chods.
Alternate pathv.rays for the synthesis of 8 vlOuld
i
I involve
the synthesis of 6a by reduction of 5 with lithium
i
I
I
•
alum~num
Iphorus
I
!i give
!
•
I
)
hydrJ.de
\LAH
•
Reo.ction of compound 6a vJit.h.
phos~
tribromide or tri.ph£;:nylphosphine
dibromide could
.
.
6b or,,;hich upon undergoing a Hurtz reactJ.on
' yield compound 9.
16 17
'
\VOl;..ld
The strained cyclobutane ring of com-
pound 9 would then be made to undergo a photochemical ring
cleavage in an attempt to obtain 8.
32
Thermal ring
cleavage of 9 to give 8 might be possible through the
!agency of inorganic complexes of rhodiurn 37 or through sil-
lver ion catalyzed cleavage.
In addition to compound 8, the.
!catalyzed ring opening may also give 30 and other similar
I
! cleavage
compounds..
I
I ion-catalyzed
I
!
! cuba.ne system.
'
t. ••
~-~
---·--·- ----·-···-- ... ---~~---··--~-----~~-
Eat.on and
co~workers
have used such
react.ions and obtained similar results on the
41
·-----~----- ---·----·~·--~--.··-~ ... ·--~-------~------·----------·~-------··-------~---·----
-------~-------·-·--
--·
._ .•.• -.
-· · - - · · - .•.
r--------------···-···--·······-..
.
................................................................. ---- . . ..
·------~-------- -··--·----·--········--------------~------------------------------
I
30
I
I .
.
iFJ.. nally, should these routes faJ.l the elegant decarhmtyla-
.
'
22
ltion :r·eaction studied by Barton and co-workers
involving·
I
!iodine and lead tetraacetate would be used on ?a.
The
[resulting diiodide could then conceivably be converted to 8
1by a zinc dust distillation.
I
lx
X
I
3 -----)
!x
X
;
R2
11 a X
b X
X X
12
-
H
-· Br
z
~·
"'
ioa
z
lOb
z
- -co 2 H
The entry into other polycyclic systems besides that.
tetracyclodecane could also be achieved through compound
Photoa.ddi tion of a molecule of ADA to 3 might give lOa
or lOb dE;pendi.ng on 'tvhether the addition is parallel or
,perpendicular. At least two such reactions of the perpen'
21
.
1 ar nature h ave b een reporte d u1
.
d ~cu
t h e 1'~ t.erature.
On
the other hand, ca.rbene addition to 3 utilizing the
26
27
Simmons-Smith Reagent
or phenyl.(tribromomethyl) mercury
should gi. ve compound lla, b \vhich upon reduction with zinc
i
would conceivably yield 12.
•r.he intermediate 14, useful as.
!starting material for a number of other syntheses, could
i
:also
be obtained from 3 by the synthetic path\•Tays shown on
I
I
II the
follmving page~
I
I;
i
The
b:cornina~tion
of corupound 3 by standard rnethods
20
should give the tetrabromo adducts 13a and 13b
and per-·
!
I
!haps the dibromo adduct 13c. 20 , 250
Dehydrobrominations of
i
!similar
systems have been described extensively in
l
i
Jliterature&
I
I
jaffected by
20 25
,
The conversion of 13 to 14 would be
'
perform~ng
a 1,2 or a 1,4-elimination reaction
l
!with reagents such as alkoxide or tertiary amines.
I tion
th~
In add~
to these standard reageni.:s such exotic systems as
I
! hexamethylphosphoromide (Hr-1PA) , diazobicyclo [3. 4. 0] nonene·-·5
i
I (DBN), and lithium chloride·~dimethylformarnide could be used
f
[to effect t.his transforroat.ionG
l! vmuld
be the me·t.hod of choice, but: two alternate pathv;ays
I
!would also be investigated.
i\,"-
The above synthetic pat..hwa.y
'·~<-.~~----~~~·
'' ~- -<'•··-•--•·
•·~---------~•-•·•----.--"~~··-·-~··-••-••·~-··-•
The first alternative would
•••••• -··~·-•-••••-•••
"•'"""""'~-~·--••·-·
•••"••-••"•• ••••-••••-- -·-·-»••-· ''' •
-r- --•••••- ··-·--•••••"·•-••••-" -•• •-- ••
.......-.. . . . . . .
-.~-.-·--···--·--·-----······:;;··:.;
~L
. .-............ --·· ----······ ·-------------...
~ ~.
""'';};~
"""'li"" . .
--····-·-----~Ri-·---------·-----------·---~·····_--.....,~;:~OH
.
~~0
0
"
>
+
R
~
R2
.2
18
o~
. !
19b
--o
'"'"'
15
13a
1
,,•\'\\\11'·
.
0
Br
I
r'"'
~~
'
O--___,"'"o
L..-----'i'
13c
co 2H
~~OH
HO••·}
I
,.,,.
~
0
ro .F
- 2
~
+
Br
Br R-
\}
""'
~~
R2
~
~'
R2
I
I
\,JI
..
~
_,
.!..!
Proposed Syntheses of 14
14
.
-~
Br~~
..
~
l
\\'"..'·\l.
Od
.
R,.J..
Br~Br
\\\\\\'\
-.~,,,,
3
/
~~
HO~:4~J~~~~
'
R2
19a.
~.,. ~-·'".
,,,-"y"
I . ~
Br
~~~"'o!¢',Br '
\ 0--~0
16
I
HO''''l
.J
13b
14
r···-·-·--·-------------···-·-·····-····-···-..".... , ____ ....... _. ____ . ______ ...................-----... --.......... " .................................
!involve the formation of the bromolactone 15 by the r:eac·28
ltion of 3 with bromine in the presence of base.
Dehydro-;
I
i
.
~
!brom:tnataon of 15 followed by hyQ.rolysis of the dilactone
l
i\V'OUld yield the allylic alcohol 17 which would be dehydrated
I
The second alternative would
Iunder acid catalysis to 14.
I!involve
Iopening
I
the formation of an epoxide 18 followed by ring
33
to give the tet.raols 19a and 19b.
Dehydra t.ion of
lthe tetraols should then give 14.
I
The system
of
double bonds in compound 14 are ideally
I
!oriented for examination of t.he photochemical and thermal
!
!additions of acetylenic compounds.
These additions are of
ltheoreti.cal interest and would also generate a variety of
lnew
polycyclic systems.
_.....
l'·tf\~~
~
The general synthetic scheme for
s t ·ud y J.s
.
ou t· l__ 'l.ne db e 1 ov.T o
l
I
I
I
-
~--
21
14
E
20
22
24
!
~Thermal addition of DI"J11D to 14 vmuld be expected to result.
iin one or more of t.he compounds 20, 21, and 22.
!
23
Com-
i
!pounds
20 and 21 would arise from parallel and perpendic~
l
!
iular addit.im1 respectively of one mole of DivlAD to l4a
i
Com-
l
!pound 22 would result from the addi t.ion of t.wo moles of
i1DMl\.D
i
24 f 22
Ph
' ' '
d cyc.!.oaao.:t.
.,
~ '~ ' t·J.on.
'
. o t osens1.-c1.ze
o ·
cou ld
to -', - 4 •
!either yield compounds 23 or 24 or botho
lint:eresJcing to examine the
I
Iof
photoaddi tion.
I!subjected
i
bet.·ween these modes
The compounds 2 0 and 2 4 would t.hen be
to decarboxylation by one of the techniques
lmen'cioned earlier in an
land
compet~_tion
It would be
atb~mpt
t.o obtain the alkenes 25
26 respectively.
I
Ii
E
E
25
E
26
I
!Besides the unusual properties already mentioned in connec1
i
tion "Vli th such alkenes the very rigid s-tructures of these
lt'tvO comPo'l:n:tds
make them ideal fox studying photoadditions
I
21
lof unconjugatcd dortble bonds vlith acetylenic compounds.
I
II
In addition to the synthetic aspects of this research
i
of these compounds, especially t:he syst:erns represented ·
lsome
Iiby
i
5 r B, 10, and 29, would make for
inb~resting
X-ray
features as bond.angles and bond orders.
may also have int.eresting
biolo~.rical
CHAPTER III
DISCUSSI.ON OF RESUIJTS
'l'he Diels·-Alder reactions of DMB with ADA and D.l\1AD
,went smoothly to give adduc·t 1 (83.8%) and 2 (82.5%),
Ii respectively
I
It \vas found, however P · t.hat
in high purity.
.
I the solVt"!nt dioxane gave higher yields of compound 1 and
!
required shorter reaction times than other solvents of
'l"'his was not considered unusual
lo\<7er boiling points.
since the practice of performing these react.:ions at hiqh
I
!temperatures
I!second
I
.
.:LS
standard procedure.
31
The
..
add~t~on
of a
mole of diene to compound 1 and 2 in refluxing
Idioxane
\vent. very slmr.rly 1 or not at all.
In these cases,
I
I the diene usually polymerized and the other start.ing ma.te-·
rial \Vas recovered intact.
I
Compound 3 was obtained in a
.
195.0% yield by sealing the reactants in a thick-walled tube
!with no solvent and heating them to a
~ealed tube
!approximately 170°.
similar
1 compound
r~covcred
2 gave only
~ react;ivity
of
reactions using
s·tarting material.
':Phis un-
can be explained by the nature of the reac-ting
I
! dou..ble bo:nu in 2
I
~emperature
D
A requirement of the Diels-Alder reac-·
j tion is that the alkene have electron--;,v-i thdr<.lvring groups
I
1
attached to it, so that.: the double bond will be reactive
l
•~·•• ~- ••• ·---·- o·~--~~_..,, ~ .• ,- ••••••••
~ • _. __ , '" ~-~----•·~·•- '"''"'' ~~'~""•·-----~---~-···-••·-~- ••·~-·-·•-~•~-···-• -·--•
18
on•~••·-· -~ .•
• •" - · - • - · •• - · · - - - - - · · • • ,
-~-
• • - • • • • · - · - · - , __ ,_,,,,
-~
,,., , ,
,
- • ••••
enough to undergo a cycloaddi t:ion
0
The ester groups
atta.ch.ed to t.he double bond in compound 2 may not be suf-
ficiently
t.ion o
electron-attrac~cing
to activat.e t:he bond for addi-
Probably of greater importance than electronic
effects, is that the ester groups in compound 2 sterically
hinder the reaction by preventing the react,ants from lying
. th
. .
.c
•
1n
- e proper pos1t1on
Lor react1on
to ta k e p 1 ace. 36 The
above compounds 1, 2, and 3, were obtained as white crys-
talline solidse
Identification of these compounds was accomplished by
spectral and elemental analysis.
Imethyl
It was found that the
protom• of 1 had a pmr signal at 1. 80 ppm (Figure 1) ~
'Compound 2 had pmr signals at 1.68 ppm for the methyl pro!
tons and 3.79 ppm for the methoxyl protons (Figure 2).
IThese
comp01.mds also eY.:...'J.ibi ted characteristic absorptions
lin the infrared.
i
lIPhbtochemical .Cycloadditions
.
I
Ia
Photosensitized cyclcadditions were carried out using
450
"vl
Hanovia lamp.
!sensitizers
I
Ishmved
Trial experiments using such photo-
as benzophenone, acetophenone, and acetone,
that. the latter gave the most satisfactory results~
IlA 11 1rra
·
d'1at1ons
·
were
· d out 1n
·
carr1e
quartz or vycor flasks
!'e1. ther at .c.l
~. 0 •
C or at acetone reflux temperat.ure.
The con-
version. of 3 to 5 \v<'W follmved by purr to det:ermine optimum
I
!reaction conditions.
I
Initially, the vinyl methyl protons
!of 3 appeared at 1.68 ppm.
i
As the photoreaction proceeded
r····· ··-----....---··- ---··-····--·· -··-····· ..·-------······-····---..
--·-·---~--
................ .
i
! these
methyl groups wer:e conver·ted from unsaturated to
I
!saturated methyl groups and gave rise to a pmr signal at
l
!
il.05 ppm. Aliquots of the reaction mixture were taken at
Iregular t1.me
. . 1..ntervals
.
1
I
.
I
.
1
and the rat:Los of the met_l.yl peaks
jdetermined by integration of the pmr spectra.
In this man-
l
lner it was found that the reaction went to completion in
!I about
I
.
II J.n
five days when an external light source vvas used, or
-"
when an internal light. source was used.
one ,..~.ay
I
The
.
I conversion of 3 to 5 was complicated in that several side
!I
'
i produ.cts
vJere produced besides. the desired compound 5.
I
.
!These side products included small amounts of starting
I
I material,
I
IyellovJ
11.
i t 1e2r
tet.rame:thylnaphthalene r and some unidentified
•
gums.
The first two by-products were identified by
...
.
ph
ys:Lca..~.. propert1.es.
.
,.
Tl1e separat:Lon
o f· tnJ.s
comp 1 ex
ireaction mixture was the major obstacle in this synthesis.
Compounds 3, 5, and tetramethylnaphthalene sublimed
I
readily and selective sublimination failed to
mixture.
separat~
this
Like-v1ise, fractional recrystallization failed to
!purify this reaction mixture.
Initial trial separations
!using column chromatography on silica gel and alumina par-
It.ially
sepa:r:at.ed out the te'tramethylnaphthalene but failed
!
I to
separate compounds 3 and 5.
II held
1
In fact, the alumina column
the compounds so tightly that it v-1as difficult. if not
impossible to elute them off the colurnno
II exclusive
'rhis led to the
use of silica gel for column packing.
A.fter many
I
!unsuccessful trials employing different solvent systems,
I
!
-
l .. ~----·-·--· -~-- ---~-~-·-- --~------·····- ··---.----"------- ---- ~----~------~---- --- -~----------------- ------ -------------------------- _________ ,, _________ ---------- ----------------------------"
l----------------------~------------~-----------------·-··---------------~--------------·-
Ivarious
------- -------------------·- -- .
silica gel mesh sizes, and varying weight. ratios of
I!compound
to column packing, a separation was finally
!
jachieved.
I
!
Ion
The yields reported for this synthesis \·Jere determined
the basis of the amount of 5 eluted from the colurnno
It
I
\was found that photolysis at 21°C resulted in a 40-50%
1
!yield, \'ihereas photolysis in refluxin·g acetone gave a yield
Ijof
62%. In all cases pmr spectra. shmv-ed that approximately
I
.
!98% of compound 3 ha.d reacted.
The small amounts of tetra!
Iroethylnaphthalene
!few
1
-vJhich -v.rere i.solated ·constituted only a
-
percent of the overall yield.
I1product
The forma·tion of this
can be explained by the follovring sequence of re-
i
Iaction.
l
C=O·
c
~'0·
0
Both maleic anhydride
1
42
and phthalic anhydride 43 are known
to undergo decarbony.lation and decarboxylation through
!thermal activation.
I
Other pho-tochemical transformations at·t.empted \vere the
l (2 + 2 + 2 + 2) cycloaddition of llDA and Dr'it\D to compound 3'
li
f-~- .......'"--<·~-~--<'----..--~~--~~--~-_;_- -~--~----------'" ~-~~---- ------.----~-~--~----·· -------------------------.------------------~ -----~----~------~-
--. -·-. ~- ... -- --~ --- -- .....
,~-----
.......
·--·--~·-···----·--·····-··-·--------·»----······-···--·-------····-···--··-·--- -···~·--·-·-·---·--·--···---·······
.....
........... -··· ·- ..... ··-···--·- ..
Ito yield lOa and 10 b. The literature cites at least two
21
lcases
where photoaddition reactions gave compounds of
type lOb.
. with
Irradiation under a variety ·of conditions both
and without
1,desired
sensitize~
adducts lOa or
lOb.~
failed to
~ive
any of the
Zn all cases the initial
!starting material was recovered •. The failure of these re-
I
!
!actions to proceed could be rationalized on steric grounds.;
!S.ince compound 3 gives 5 on irradiation this suggests that
Iduring the reaction. its
I (double
conformation must be as shown belo\'J.
boat).
I
!This is the only conformation in which the double bonds are
I
suitably oriented for cycloaddition to give either compound·
5 or compounds lOa and lOb.
In this conformation the
t ~~-~--~-~,~------·-.~·--·---"~--~-~----~~~~~·"···
I
j
•
--~---~----~~--·~-·-·-----·--=-----.-···-~~.,--~--~'"·-~--
•
....
-----··--·~--7---~~---·-····~~--·-
...........
-.-----··~--~--·--~---
-- _. ___ _
•
,Brom1nat1on React1ons
I!
'l'he bromination reaction of compound 3 i.:o give pre-
ldominantly
I
I
a single tetrabromo derivative v-1as expected to
.
! be straight for,•Tard since similar reactions were well doc-
!umen t e d • 34,25,16
1
I
.
.
Th'~s expectat1on
was not rea 1'J..Ze d
!complex mixture of products was obtained.
I
a
'l
anc..~.
In order to
.
!investigate this further, bromination reactions were run
I
I,
•
.
-
Iunder carefully controlledconditions employing a range of
!Solvents from carbon tetrachloride to glacial acetic.acid.
lI Temperatures were
ature.
Ia
varied from 0 °C to solvent. reflux temper-'
In all cases, bromination of compound 3 resulted in.·
quantitative yield of product (based on the addition of 2
I
!moles ~f bromin~) but consisted of a mixture of the tetra1
!
bromo J.somers l3a and 13b.
It was found that at higher
I
!temperatures compound 13b was favored and at lower
!atures
l3a \vas favored.
temper~
Attempt.ed physical separation of
I
! the isorneric mixture failed in all cases.
The isomers de-
composed on chromatographic columns and on sublimation.
Recrystallization was ineffective and the isomers were
lfound to be heat labile.
Ii: was then decided that the
in~·
ldividual isomers could be obtained only by selective
\synthesis.
1
Compound 13b was selectively synthesized by bromina-
~ tion in refluxing et.hyl acetate ( 77 °C} •
Workup of this re-
I action gave 13b as a white cryst.alline solid.
I
!determined by
I
.
pmr spectra and melting point.
\ ~- ---··-······· ···-····.. . --···-·--··· ........ -· ... -··-·· .... ···---········-··-··---· -·- ······-··-·· ...... •·····
... .
•······· ·- -· -····
Purity \vas
The pmr spec-_
.. .. ......... ·-·· ··-- ....... .
chloride at dry ice-acetone temperatures.
l
The pmr spectra· of· the methylene protons of 13a and
113b are illustrated below.
13a
t
I
!
13b
The fact that bromination gives two isomers may be
explained by considering kinetic versus thermodynamic con~
trol
~
At high temperatures the more stable isomer should
I!
!
~
be 13b (models show that i:his can exis·t as a double chair
·--~~----~--~ -~. ····---~-~- -~----~--------~-~--~-~~---~---~-~~--~·-·"··- - ~·-· ---~-.
·-···-
·-·-·-------.
-~-
----------·----- --- -··-------------
~~----~
--·-----------···------------·. ---
---~--~-----
.u. --- __
.!
r~-~-~-----·---~-----
!"''i th
-·
.
--~-~~ ~---------~----·------------
..... --------------------------··-··--·- -------····- . ···------· ---·-·-· .
~--
~--·-
all trans diaxia.l bromines) •
A.t lmv temperatures
II
jkinetic control may operate and the less stable isomer 13a
I
jshould be formed.
l
! t\vist boat
Il
·
act~ons
are
Models show that 13a should be a double
.
conforma~cion,
· · ·
m~n~~ze d
•
so that 1-2 and 4-8 bromine inter-·
T1h.
ese-Y·f
·
db y
acts are sub stant~ate
1
!the experimental results as well as pmr spectral datae
The bromination of 3 with N-bromosuccimide 35 (NBS)
!proceeded smoothly to give the ~llylic dibromide 13c. 16
I
I.
!The is01neric forms of compound 13c were not separated and
l!the
crude material was used directly -vlithout further puri-
lfication in the dehydrobromination reactions.
A tetrabromo
'adduct derived from the addition of four moles of NBS to 3
\1/'as also prepared.
This tetrabromo adduct was then sub-
ljected to a photosensitized cycloaddition as shown below.
3"
-~
13d
31
It was hoped that the conversion of 13d to 31 could be
effected, since compound B would lend itself to conversion
into a pentaprismane system as shovn1 below.
Initial
attempts to effect this conversion v1ere unsuccessful.
.
..
r-----·-----···--··---~-·--·····--·-·· ---·-·--------~-----···Ri~······n.2--~-·-~---
I
······--·--···-->······················-·-·-··--·····
Vi·
IiReactions
- .
of Photoa.dduct (5)
It was originally intended to hydrolyze the photo-
I
adduct 5 to the diacid 7a by use of an aqueous acetone
I
.
Iso~ut~on
17
&
However, it was found that even prolonged
•
jst~rr~ng J.n hot aqueous acetone failed to hydrolyze the
I
lanhydr~de bridge of 5~ Basic hydrolysis of 5 was then
I
!attempted using methanolic NaOH. The diacid 7a was
1
obtained after workup, but. spectral analysis shov.red it to
Jbe
contaminated with small amounts of the half-ester.
To
!avoid the formation of the undesirable ester side product,
I the
photoadduct 5 \vas finally converted to the diacid 7a
I
!by use of aqueous NaOH.
A quantitative yield of ?a was
i
Iobtained.
IR analysis showed it to be uncontaminated with
I
!either ester or anhydride side products.
Compound 7a was
Iinsoluble in almost all solvents with the exception of D!A.SO,
!acetone (slightly), and acetonitrile (sparingly).
1
I
1
The pmr
spectrum of the diacid 7a is shown in Figure 6.
The conversion of the diacid 7a into the alkene 8 was
attempted using the anodic decarboxylation techniques
I1 d eve 1 opec."
I
b y Ra dl ~c
· k ana"
Idecarboxylation
co-~vor
k ers. 17 a' c
•r1. 1e
· ·
orJ.g~na
1
reaction gave-; a tan colored solid t,.vhich on
L___ -.......... ~---- -· .--- ------·----- ·---·--···----------·· - - -- .··--···--- ·-·-· ..... -·- · . · --·---·- · · · · - · -·-· ·- ---
r~~·-~~·---·-------~~····· --~~-~- _,.,......·-~-~~----~-~"-~··-----~~~---~-·=-~-·-·
....
-·---~·~-----·------------~
.......-
···-·---~··--·-
'
._ -·
--"·---~·-
!recryst.allization gave a t.'ilhi te crystalline solid.
..
r
···-
~·-··"-
......... -·-·
••
Spectral·
I
;analysis of this solid shov.red that i.t was not the expected
!alkene
8 but the lactone 27.
l
i
!
0
l'
. II..
_- ~~ '.~~
i
I
I
27
I
lIdentifica·tion \vas
I
Ishm, ed
7
based on the infra.red spectrum which
a carbonyl absorption at 1815 cm-l and the pmr spec-
j truro (Figure 11) \<.7hich shovled that there· were more than t'vo
!
iI eaui valenJc sets of methylene protons (alkene 8 should have
d
.
l
lt\170 equivalent sets of methylene protons).
Anodic decar~·
lboxylation of a second sample gave identical results to the
I
I
i
1above*
It was then hoped to synthesize compound 8 by use
!of-iodine and lead tetraacetate, a procedure extensively
I
lst~died by Barton and co-workers. 22
Initial trial experi-
lments using this reagent look promising.
I
Compound 5 was converted to the diol 6a in quantita=
!tive
yield by reduction with LAH.
l
Reaction of this diol
I
!with phosphorus tribromide gave a product believed to be
l
jthe dibromo derivative 6b.
l
Spectral analysis of 6b was in-
l conclusi.T,re in identifying its structure.
The pmr spectrum
J
I {Figure
'
13) shovred a s.inglet at 4. 39 ppm and an apparent
-.:t -~:~-~ ;~:~- ~:-~~d-:~~0:·:~~-:-~~~~~~=---~~---~~~-- --
1
~:~~1:~
1additional
methylene hydrogens \¥as not characteristic of
jthe tetracyclodecane system {Figure 4).
Compound 6b failed
Ii to
underqo a· vJurtz reaction to give 9. Instead the vJurtz
8
Jreaction gave a mixture of unidentifiable products includling starting materialo
I
It is believed that 6b may be the
jmonobromide even though IR ana.l:sis was inconclusive as to
jw?ether alcoholic functional groups 'tvere present.
j tional
Addi-
syntheses of 6b "Jere attempted using phosphorus
lpentabromide and triphenylphosphine dibromide but were uniSUccessful.,
I
Optimum conditions for the above reactions involving
j the anhydride bridge of 5 \'lere det.ermined by trial runs
!using adduct 3 as a model compound.
lpehydrobrominat;ion Reactions
The literature contained several examples of success!
lful dehydrobromi.nation reactions on compounds similar to
1
113o
16
Attempts to obtain the double diene 14 from 13a by
several different dehydrobromination techniques were unsuC-'
,cessful.
The methods tried involved systems ranging from
Itertiary amines
to methane lie KOH, 1i thi um
jDBN, and HMPA.
The
!
.
n~$Ul ts
chloride-D~IF,
obtained .varied greatly depend-'
ling on reaction cond~tions, especially the temperature.
I
I The
major competing r:eactions were found to be molecular
I
lb
.
.
.
39 wh.en using DHF as sol VE:;-:nt, reverse
l rom1ne
e 1'1m1nat1on
I
.
.
:
IDiels-Alder reactions at h1gh
tempe:r:atures, 20 and f ormatJ.on.
l
}..,.... ,~.~~.-
--~----~·,_....,._~•••po_.......,.
__ _._,.~-·-----~··~-----~~~-~~-·-~-~~ ~~~ ~-~~-- ·-~-·---,..,~.,......_.... _o~...-.>·-·~···-<~-~-~·-- ...... •=·-~ ··--····~·~···
jof exocyclic double bonds.
~-
•,
o~----·-o>oAO ">~••'" o , --~---·••
The formation of exocyclic
!
jdouble bonds would give a variety of compounds similar to
Ithose
shovm below.
..
I
These compounds would arise from the trans elimination
1
rr~thyl
!of a
hydrogen. Reverse Diels-Alder reactions gave
!
)4, 5-diroethylphthalic anhydride, which -vJa.s iden·tified by pmr'
l
and infrared spectraQ
The best results in all cases were
is possible that this type of reaction could lead to tetra.cycline systems which may possess useful biological prop-
!erties.
The above reac·tion products yielded pmr spectra
1with signals in the region of
alkene hydrogens.
s. so
ppm, characterist.ic of
The yields of total products were on the,
order of 8~-90% bas~d on eliminati~n of four.m~le~ of HBr.
l
1
The sJ.de reactl.on·s could possJ.bly be ell.mJ.nai:ed by
use of the dibromo adduct 13c.
In this compound the
tbromines are situated so that they cannot undergo molecular
I
!bromine elimination.
Moreover, 1,4-·eli.mi.nation to give the
J
!double diene 14 may be favored over elimination involving
L..... _.............................................................._. . . ____ "'........ _. _________. . .........................
-........................................ ----- ................................................
,-------·----·-·---····-··
I
!
·--·-·--·-·-·-·-~-----------~-------··---·--
the methyl hydrogens.
..----·--··---··---··---·---------------·-·--·· ......................... ----.... - . .
.
It. migh·t also be possible to elim-
linate these side reactions by using tetra-n-butylarnmoni.um
I
1
bromide
I
44
for t.he dehydrobromination of l3a,b.
The bromolactone 15 v;as obtained by addition of bro-
28
.i m~ne
.
1' .. n b ase.
.
.
.
9•
Th e pmr spectrum 1.s
s h own 1.n
FJ.gure
I
i Dehydrobrm[tination
llcou1d
then be converted to 14 via the dehydration of the
I allylic alcohoJ_ 17.
!was
I
of 15 \vould be expected to give 16 which·
P~n
unsuccessful~
attempted conversion of 15 to 16
!Miscellaneous Reactions
~--~o;:nd -;-~~as
reduced to the diol 28 by LAHe
The
!yield of 28 \vas quantitative and identification was
'
obtained b:y· spectral and elemental analysis.
!truro of compound 28 is shown in Figure
10~
The prnr spec-
Reaction of 28
lwith phosphorus tribromide gave what was thought to be the
Idibromo
der.i va t:i ve 2 9..
Compound 2 9 existed
as
a liquid and
i
!was identi£ied by spectral analysis only.
II stablE~
and the pure compou.nd \'lhich was a clear liquid
Ichanged to
!hours~
It \lms very un-·
a yellow liquid at room temperature in a few
Elemental analysis could not be obtained on this
!compound due to its instability.
I
I
IL~.---~--·--·--·-·- --------------------..--.. -----·-----------·-- -----~ .............----------..-·. - .... ---..--.. -·---·· ---------------·- ------·---·-- . . . ..... -----
1
·,
l3
----)#
----7»
i
!
I
CH 0H
2
CH 2Br
II
28
29
I
I
I
I! The pmr spectrum of 29 is shovm in Figure 12
G
The above
syntheses of 28 and 29 were carried out as trial runs to
Iobtain optimum conditions
for similar reactions on the
.photoadduct 5e
I
The conversion of compound 3 to compound lla was also
.
.
. h reagento 26
at t ernpte d us1.ng
t. h e S:unmons=Smlt
.
'l'h1.s
conver-
to be unsuccessful and starting
Ilsion oroved
~
. - material was
!recovered in all cases. The failure of this reaction to
I
!proceed might be due to steric interference by the methyl
!
'groups or to deactivation of the reagent by the anhydride
:bridge.
It is knm>Jn that the SimmonsuSmith reaction is
!facilitated by a hydroxyl substituent in the immediate
vicinity of the double bond 40 and it is believed that this
is due to coordination of the oxygen with the
I .
reagent.
Si~nons-Smith
In compound 3, the anhydride group is probably
not close enough to the double bond and probably does not
I coordinate as v1ell with the Simmons-Smith reagent, thus
~causing the reaction to be unsuccessfulo
An alternate con-
'jvers~on
. of 3 to llb might be effected through the use of
j phenyl{tribromomethyl)mercury. 27
Ini'cial experiments "Vlith
!
! this reagent have shown promise.
!~--·-·---------····-·-··· -· ----··-----·--·---·------··-----·--·· --··-----·· ---··--·· · --·-·----·----·-----------· --·-·-----·· -·· ·-· - - ·- ·- - · -.. . -· -·- - --
CHAPTER IV
PRO'rON HAGNETIC HESONANCE SPECTRA
l
l
j
All of the pmr spectra were obtained in deuterated
Ichloroform at
34°C unless sped..fied othervlisee
The scale
I
!of the spectral reproductions is 1 em= 30Hz. All values
I
I for the pmr signals are expressed as ppm dmvnfield ( o) from:
I
I
itetrarnethylsilane
as internal standard.
.
I
I1for rnul tip lets
Chemical shifts
\vere obtained by first·-order analysis only.
I
I
32
·--,i
i
!'
I
I
I
I
r-1
ru
§
0
~·
0
u
!
;
!
I.
-·-~~·---
······-····-·· ...J
r···-"'"'-·-~
..
·"----~--~····-----
.... .
i
1
I
lI
'
Il
I
I
l
l
I
!
lI
II
l
I'
I
I
I
I
l
I
I
l
II
I
I
l
!l
I
I
I
I
N
'U
~
::~
I
'i
l
{)
t+r
E~
0
0
.
~ ~--~~~-~~~-·---- ~- -~ ---··~~---
... -~ -~~-- ·--·-· --~--~---· --~ ·-~-~-~~ .. ····--- -'""·-~
----~--- --~<~-~- ~---··-----··
"'""""
---:._
"""
;~\
"""
~....,
..:&
I
I
I
I
I
I
L,~··
~
....._:__,
r~--
1
!
!!
I
1
I
I
l
l
I
I
l.f')
't5
§
0
ft0
()
·----~···---~
r--··~· ··-··----------·-~---··---·---·---------·-----
1
.
. -·--·········--·······
·-~-.--- --~---·
. ·-·-.. --·· ·---· ···----··--·····-··--··-· · -
.
--~
I
1.{)
--~-_j
0
U)
~
Q
I
\.0
1\1
'U
'0
s:::
~
0
())
F.:
r-i
1-
::J
~l,
0
u
s::
:>
0
U)
.. .i
i" '·"··-~~~···-·~· .-~····-..
I
!
I
!
I
II
I
II
I
i
l
II
1
I
I!
i
'
I
l
I
i
1
I
I
•••--H--.o,Oo_< __
j
f-
!
I
I
I
I
-I
I
i
t
a;
N
'lj
§
0
q.
H
0
u
CHAPTER V
EXPERH·ffiN~'AL
General
Melting poin·ts \V'ere obt.ained on a Thomas-·Hoover melt.appara~us~
ing point
obs(~rved
The values are uncorrected and were
for samples in open capillary tubes.
The infrared spectra -vmre obtained with a Beckman IR-8
Infra:r.:(~d
Spectrophotometer: arid 'ltlere run in deu'cerated
chloroform
~~less
othenvise specified.
Ultraviole·t spectra \\rere taken using a Perkin Elmer
Hodel-202..
Ali ultraviolet spectra were run in 9.5% ethanoL
The proton. magn.etic resonance spectra \>.7ere recorded on a
Hitachi R·-20 high resolution NH..~.~
60
MHz~
spectromet~er,
operating at
Spectral v.:1lues are recorded in ppm (6) relative
to tetraraethylsilanec
'I:he D.HJ3
WetS
prepared according to procedures given in
S?r~la~?.:_~. Synt,E.E:!~::!.:.~~.L.S~~~c!.i'!_;::_Vo_lume III_.
The DI•JAD used
was purified by distillation under reduced pressure and
then stored in the refrigerator.
Acetone and dioxane we:ce
reasrent g·rade and were dried over molecular sieve (I,indy
4A)
before use ..
46
Procedures
Acetylenedicarboxylic acid (23. 3 g, 20 ~ 3 romol) and Div<JB
(17e0 g, 20.8 mmol)
~~p1Ac-vJ'Ina~o1•r
;• C<l-'
• .J.-. - ' '"'"'' ... ~
'
24
hr •
.•
~-vere
dio}~ane
heated in 40 ml of
for
At: t:he end of th:Ls time the solution
! was cooled to room t:emperature and
ner:.;dJ.e-like crystals of
'
I' the
1:1 adduct crystallized out of solut.ion.
I
i mixture
t'las
I
Ile~her-other
-.. . ·- ...
~·
~
The reaction
filtered and the crystals were washed vlith pet
The resulting filtrate was evaporated on a
I rot.ary evaporatm: an. a the cx:ystalline 1: 1 adduct v1as
I filtered and v;rashed as above~ The total yield \•laS 13. 8
!
!
I (82.5%). Recrystallization
I
I nE:~edle-·li.ke crystals of 1:
g
:from ethe:r>,pet ether gave clea.r
mp 167.5-16 fL 4"
(lit~. 45 16 8~
!
I 16 9 ° ) ;
i :c 1.8 4 5 , 17 7\l ,f 14 31 crtt-l ; pm:c {CDC 1 ) 1 • 8 0 ( s , 6 H,
3
I mei.:hyl
protons) , 3. 02 ( s, 4H P .methylene protons) •
I
I: Dimethy1=4, 5···dimet:hy 1-3, 6-·dihydrophthal.at.e
i ___'"_. ,._..__,__________
(2)
.. -·--
-------·--·--~---·---···~-·--·-----
Dimethyl acety1Eme1.icarboxylat.e (5.01 g, 3So0 nmlol)
1
i
I was added t:o 3 •. 00 g {36.6 mmol) of DMB in
i
! excess of
orator.
(1 .],.. '\<........
(f:ir
A slight.
.:)
t.hon added and t.he mi.:t;:ture re :c'"1 11X~<:'! '..t
f!'
Recrystallization of the crude product yielded
/'' s· "75 "C'CI\ b
...~·/\)
Ji
p
~.
e~t:her&
1Qr!
·"
t.~ 110°
. ••
4H 1 n1ethyle:ne protons}
1
(0~ 6'"" n1m
- );
&
'
~' r..
17~0"
~
, 1-672
, ,,
3.79 (s, 6Hr ester mo;;tlwxyl
Add1.w·t 2 was placed in a sealed t.ubl'! vd t.h an equimolar
. amount of diene and heated overnight at 160° ~
Workup of
·the reaction mixture yielded starting materials only.
3!. 4, 8 L9-Te~~~-cyc1:o [ 4 o~~_-3 1 8-diene-1 r 6-dioic
: l;nhydride (3)
-·.,......,~----~,.,.....,..~~-
Compou.nd 1 was placed .in a thick-walh.:d tube with a
Blight excess of DJY'ill e
dry
ice~·acetone
The tube, \'l?'aS partially immersed in a
bath, flushed with argon and then sealede
The contents '\\7 erc heated at 165-180° for 48 hr.
At the end
of this period the cooled tube was opened and the solid
material wa.s crushed to fine crystals, filtered and then
washed wit.h ether to remove all traces of colored
tieso
impuri-~
This process yielded 95.5% of extremely pure white
crystalline material identified as 3.
Recrystallization
from ethc-:r-pet ether followed by drying (P o ) gave a mp
2 5
152-153.5°; ir 1845, 1770f 1440 cm-lp prnr (CDC1 ) 1.68
3
(sf 12Hr methyl p:cotons}, 2.20
rnethylene prot:ons)
'''1a1
f
(d, 4H, ,J = 4.5 Hz 1
2. 38 {d; 4H 1 methylene prot.ons).
C"1lc"'
C 'L"" ·~r
0 ".•
c.
...,. • fov·
'~"·20
- 0
~)
.~.,
·-.
-·-·-·
c,
Found:
73.84; H, 7.87.
3 r. . ___
4, 8 r ,_9·-Tc'i:ra.methyl
tet:r.acyclo
__
_..,._ . . . . . . . . .
. . - . [ 4. 4 ~ 0 ~ 0
_,_,~·-·-~·-----
dioic .... 11.nhvd:r-ic1e
----...... .... .....
~-
........,
~
( S)
,~ .......... ~-----~·
Compou.nd 3
3 9 4 8
' • 0 ' ] decane·-1, 6·-
-·-------·F-,~.z.--------·----
.......
(6~29
gr
24.2 mmol) and 300 ml of aceton(:3
were placed in a quartz flask and photolyzed under nitrogen
vvi th a 450 vl lL:.movi.a. lamp for 6 days.
removed \d t.h a ro1;a:cy
evapor;;~tor
an<'J.
·The acei:one was
'cht~
sub~Hxp.Jf~nt
crude
reaction mixture chromatographed on 100-200 mesh silica gel'
; packed in 100% pentane.
The optimum vJeight ra·tios of col-
:umn packing to reaction material was found to be on the
!order of
so-ioo
to 1.
The sample was applied to the top
!of the column by dissolving itin methylene chloride and
'adding to this solution 3-4 til-nes its v..reight of silica gel.
Removal of the methylene chloride under vacuum then gave
solid dry silica gel on which the sample was absorbed.
This solid sample wa.s then placed on top of the column for
separation*
Elution with a 3:1 pentane-methylene chloride
mixture yielded small amounts of tetramethylnaphthalene.
Elution wi t.h 1: 1 pentane-methylene chloride gave unreacted
3 and elution with 1:3 pentane-methylene chloride gave
3.92 g (62.5%) of white crystalline 5.
Further elution of ;
the colunm gave a yellow. gurnrny residue and small an.1m.mts of
t.he diacid of 5.
The above procedure was very critical in
separating the reaction mixture and deviation from this
procedure resulted in poor separations.
Recrystallization
of 5 from methylenE' chloride-ether-pet ether gave clear
colorless crystals:
mp 2l3c5-214.5°; ir 1865 (shoulder),
·-1
1830, 1780, 14!55 em ; pmr (CDC1 } 1 .. 05 (s, 12H, methyl
3
protons), 1.38 (d, 4H, J
=
lloO Hz, methylene protons)
2.00 (d, 4H, methylene protons).
Found:
c,
73.83; H, 7.90.
r
2:..L~.:::~~d:~y~·tl2Yl-L.:]_t 4 ,_B r ~=~~~!:~.¥~1 tetras_lc lo [ 4 ·1~
o
o___
____
_____
3 9 4 8
' ,.,,....
' Jdecane
..
(6a}
....
.......
,..,.
------~_...,
Compound 5 (1 ~ 7 3 g, 6. 65 mmol) in 25 rol of
added
drop'.,dl~e
•.rHF
was
to a stirred refluxing solution of 0. 63 g
r.AH in 25 rnl of THF
'I'he mixture was reflu:xed for 24 hr.
6
Excess LAH was decomposed by adding ethyl acetate until
t:here was no vigorous reaction, then saturated aqueous
sodium sulfat:e \vas added until the reaction mixture started
to coagula-te.
A.t this time solid crystalline sodi urn sul-
fate ,..;as ad.ded until all remaining LA.H -v.Jas decomposed
(v7hitf"~
gra:rn.i.lar solid left in flask).
'J~he
solution vJas
filtered an.d the residue was v.mshed wi·th warm THF.
The
filtrate was dried (Mgso ) , filtered, and evaporated on a
4
rotary evaporator to give 1 .. 58 g (97 .0%) of 6a as a vlhite
crystalline solide
ether
gave~
Recrystallization from chloroform-pet
mp 167. 9-·16 8. 7°; ir 3650, 3400 (broad) , 1220 r
1030 cm- 1 ; pmr {CDC1 ) Oe52 (d, 4H, J
3
=
11.3 Hzf methylene
protons), 0.95 (s; 12Hr methyl protons), lo92 (d, 4Hv
J ""' llv3 H:z, methylene protons), 36.81 (s, 4H, hydroxymethyl
prctc.n.s)
P
tL05
(s, broad, 2Hr alcoholic protons}$
lm.aJ.., Calc& . . for c
Found:
c,
H o :
16 26 2
C, 76 .. 75; lip 10.47.
77.10J H, 10.67.
•.ro 1 ~ 98 g ( 7 o 61 :mmol) of 5 dissolved in 85 ml of
, d.iethyl
eth.E.~r r:ms
added 10 ml of 3N Nao:f-I.
The resu1·ting
'
~solution was stirred for 24 hr •.
At the end of 24 hr, the
ether \'las removed and the sodium salt of the acid was dis-
solved in \\later.
~'he
aqueous solution was cooled, acid-
ified wit.h concentrated hydrochloric acid, and filtered.
'fhe resulting v.1hite solid \vas dried (P o ) to give 2.09 g
2 5
Recrystallization. from DHSO-H o gave:
2
mp 216.9-217~1°; ir (n.ujol) 2900 (broad), 1711 cm- 1 ; pmr
(98~
7%} of 7a.
(d 6 -DHSO} 0.92 (s, 12H, methyl protons), 0.99 (d, 4H, J =·
12 Hz, methylene prot:ons), 2.00 (d, 4H, me·thylene protons).
Found:
C,
: H,
(13a)
Compound 3 (1.00 g, 3.85 mmol) was dissolved in 25 ml
of ethyl acetate, cooled to 0°C, and·0.60 ml of bromine in
5 ml of ethyl acetat.:.e \Alas added dropwise.
The reaction \rJas
stirred for one hour at 0°C and then filtered.
The solid
was washed with cold ethyl acetate and then ethero
tallization from methylene
\vhite crystalline solid, mp
worked up as be.lovJ ~
chloride··~pet
Recrys-
et:.her gave 13a as a
168~5-·169.5°0
'l'he filtrate \'\las
Compound 13a may also be obtained in
almost quanti tat.ive yield by brominating in m:::.d:.hylene
chloride at dry ice-acetone temperatures.
1425 em-·1 ; pmr (CDC1 )
3
(sr
2~05
Ir 1855, 1781,
(s, 6Hu methyl protons), 2.25
6H, methyl prot.ons), 2.82 {d, 4H, ,J ,,., 11.2 Hz,
methylene protons), 2.89 (d, 4H, methylene prot.ons).
(13b)
To a solution of L 00 g
(3~
85 rnmol) of 3 in 20 ml of
ethyl acetate ''vas added 0. 60 ml bromine.
refluxed for 15 minutes.
The mixture vms
After 15 minutes the reaction
rnixture was cooled, washed once with vlater, once wit.h.
saturated sodium bisu1fi Jce, and twice more with \vater
'l'he
0
ethyl ace·tate solution vias dried (NlgSO ), filtered, and
4
evaporated partially on a rotary evaporator.
The resulting
mixture was filtered and the solid obtained rec:t:ystallized
from methylene chloride-pet ether to give 13b as a whit.e
-1
crystalline solid:
mp 171-172°; ir 1855, 1775, 1425 em
;
pmr (CDC1 ) 2.04 (s, 6H, methyl protons), 2.07 {s, 6H 6
3
methyl protons), 2.07 (s, 6H, methyl protons), 2.35 (d, 2H,
J
= 17.3
Hz, methylene protons), 2.78 (d, 2H, J
methylene protons),
2~79
(d, 2H 1 J
= 16.1
~
17.3 Hz,
Hz 1 methylene
protons), 3.57 (d, 2H, J:::: 16.1 Hz, methylene protons).
In both of the above procedures the overall yield of tetra·bromo adduct:s vms quanti ta ti ve.
Anal. Calcd. for
Found:
C,
32~95;
c 16 H20 o3 Br 4 :
C, 33.14; H,
3.48~
Br,
55~11.
H, 3.72; Br, 54.96.
To a solution of 2.21 g (8.50 mmol) of 3 and 2.00 g
(35.7 mmol) of potassium hydroxide in 50 ml of water and
50 ml of methanol vvas added 1. 80 ml of bromine.
tion t:urned red and a -v.rhi te solid formed.
The solu-
'rhe reaction
mixture was decolo:r:.Lzed vlith satura.ted sodium bisulfite,
· v.rashed with water, and extracted \vith methylene chloridee
I.
' 'l'he methylene chloride ~v-as dried (}~gSO ) , _ filtered, and
4
t11e solvent vlas removed vli th a rot:ary evapora-tor.
• i.:a.llizat.ion of the crude prodcict
'gave a v1hite crystalline solid,
1
(dec); ir 1785, 1491 cm- ; pm:r:
i
\r.J"i t.h
Recrys-
methylene chloride
(15):
.<cncl 3 )
mp 25868··259.8°
1.67 (s, 6H, methyl
protons), 1.87 (s, 6H, methyl protons),
2~02
13o8 Hz, methylene protons), 2.12 (d, 2H, J
(d, 2H 1 ,J ·-
=
16.6 Hz;
methylene protons), 2.70 (d, 2H, J = 16.6 Hz, methylene
protons), 3Q65 (d, 2H, J:::. 13.8 Hz, methylene protons).
~!_1~1. Calcd. for
Found:
c 16 H20 o 4 Br2 :
C, 44.06; H, 4.62; Br, 36,64:
C, 44.23; H, 4.34; Br, 35.31.
Compound 3 ( 6 ~ 39 g 1 25.5 Inrnol) in 55 ml of THF
~vas
added drop"t-,rise to a st:irrec1 refluxing solution of 1. 62 g
of LAH in 50 ml of 'I'HP.
Workup as: above gave 5. 85 g (95. s~.n of
fluxed for 24 hr.,
v;hi tB cryst.alline 28 ~
pet:. et:J:wr ga:vc."!:
The reaction mixture was then re=·
mp
Recry~;tallizat:\.on
157.0~157.9°;
from chloroformM
ir 3300 (broad), 1280,
1079 cm- 1 , pmr (CDC1 )· 1.59 (s, 12Hp rnethyl pro·tons), 1.92
3
(s, 8H I' methylene pro'l.:ons) , 3. 52 {s, 4H r hydroxymethyl pro-.
tons), 4.05 (s, 2H, alcoholic protons).
Pound:
c,
76.73; H, 10.11.
c·
_____
•.tmodic __Decarboxvlat:ion
of 7a to Yield 27
._.
....,.__...,....
-·~--
Co:mpmJnd 7a
(0~605
g,
2~18
mmol) was dissolved in 10
ml water, 90 ml pyridine, and 1.25 ml of triethylamine.
'I'he resulting solut.ion was subjected to elect.rolytic
decarboxylation tmder a nitrogen atmoFphere according to
·
17a c
the procedure of Radlick and co-workers"
'
current \vas 0.15 A at 90 V.
'I'he react.ion
'l'he initial
tempe:r.~ature
v.ras
After 5 days the reaction mixture was extracted
13-15 c·c e
with pentane.
The pentane was \'lashed with water, cold lH
HCl, and saturated
NaHC0
3~
The pentane
~·;as
then d:cied
(Hgso ), filtered, and the solvent \'las removed under
4
reduced pressure to give 0.269 g (53e4%} of 27 as a white
crystalline solid.
mp 246 .l·-24 7 .. 1 °.
Recrystallization from hexane gave a
The same procedure repeated for 29 hr on
another sample of 7a gave 51.0% of 27.
pent.ane was not washed vlith acid or
13l5 em
-1
; pmr
In this case the
bicarbonate~
IR 1815,
(CDC1 ) 1.02 {r->, 12H, methyl protons),
3
1.00~
2.50 (m, 8H, methylene protons).
AnaL Calcd. for c
Found:
C1
H o :
15 20 2
C, 77e55; H, 8.68.
77.46; H, 8.42.
Del:~yd:robr::nt~:2':.~:ti~£.._1.3. t_9__..9i ve 14
Compound 13 {2o56. g, 4.57 mmol), 1.44 g (24.8 mmol)
KF, and 12 ml of I-Il'-1PA were placed in a 25 ml flask and
heated at 90-95°C for 27 hr.
'l'he reaction mixture vvas then
pour<::!d ini.:o v.Jater and was extrac·ted
'"'i t:h
pentane.
Aft:er
drying (Mgso ), the pentane was evaporated to give 0.946 g
4
( 81% based on elimination of 4 moles of HBr) o:E a v1hi te
crystalline solid.
This solid was then chromatographed on
100-200 mesh silica gel packed in 100% pentane.
Elution
•\vi th 10% ether~·pentane gave a whit:e solid vvhich on recrys, tallization from hexane had a mp
127~~130
°.
Spectral anal-
· ysis shm·;ed that. this was not the expected diene 14.
pmr spec·trum shmvs alkene signals at 5. 40 ppm.
'rhe
Infrared
analysis confirms the presence of an anhydride ring.
Miscellaneous Reactions
Phenyl(tribr.omomethyl)mercury for use in converting
compound 3 to 11 was synthesized by the method of Seyferth
.
27
and Burlitc:h.
•rhe Simmons-Smith reagent was prepared by
the method of I.e Goff. 26 a
The synthesis of the dibromo derivative 29 was carried
out as follows"
A mixture of compound 3 (0.921 g, 3.68
mrnol) and phosphorus tribromide (0 ~ 23 ml) was v.rarmed and
then •rHF was added.,
minutes and
thE.~
was disi:illed
pnrr {CDCl..,}
.:;
8H,
The mixture
't1aS
refluxed. for 15
sol vent removed under vacuum.
usin~r
The product
a molecular s'cill to give 0. 864 g of 29;
1&61 (se 12Hf methyl prot.ons), 1.80-2.40
met~hylene
(m,
p.:r:otons), 3.67 (s, 4H, bromornethyl protons).
The attempted synthesis of 6b was carried out in a similar
manner~
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