Chapter 3
Compounds with Carbon–Sulfur Single Bonds
I.
II.
III.
IV.
V.
VI.
VII.
VIII.
IX.
X.
I.
Introduction ........................................................................................................................62
Reaction Mechanisms ........................................................................................................63
A. Group Abstraction ....................................................................................................63
B.
Electron-Transfer .....................................................................................................64
Alkylthio and Arylthio Substituted Carbohydrates and Related Compounds ...................65
A. Simple Reduction .....................................................................................................65
B.
Radical Cyclization ..................................................................................................66
C.
Ring-Opening Reactions ..........................................................................................67
Dithioacetals ......................................................................................................................68
Thiocarbonates and Dithiocarbonates ................................................................................69
O-Thiocarbonyl Compounds .............................................................................................70
Sulfones..............................................................................................................................71
A. Addition-Elimination Reactions ...............................................................................71
B.
Electron-Transfer Reactions .....................................................................................72
1.
Samarium(II) Iodide .......................................................................................72
2.
Chromium(II) Complexes ...............................................................................77
C.
Sulfone Synthesis .....................................................................................................78
Thiols and Thiyl Radicals ..................................................................................................78
Summary ............................................................................................................................80
References ..........................................................................................................................81
Introduction
A carbohydrate derivative that contains a sulfur atom bonded to two carbon atoms is capable
of forming carbon-centered radicals. A common pathway for radical formation in compounds of
this type is homolytic cleavage of a carbon–sulfur bond brought about by group abstraction (eq 1).
When the sulfur atom in a C–S bond is part of an electronegative group, as is the case in a glycosyl
phenyl sulfone, electron transfer of the type shown in Scheme 1 represents another pathway to
carbon-centered radical formation. A beginning point for discussing these reactions is examining
their possible mechanisms.
O
O
+ Bu3Sn
SR
OAc
R = an alkyl or aryl group
+
OAc
Bu3SnSR
(1)
Compounds With Carbon–Sulfur Single Bonds
63
Scheme 1
O
O
D
- C6 H5 SO2
O
-D
SO2C6H5
OAc
SO2C6H5
OAc
OAc
D = an electron donor
Scheme 2
R1
R2
R1
S +
SnBu3
S SnBu3
R2
+ R1SSnBu3
R2
+ R1SSnBu3
R2
Scheme 3
R1
R1
S + SnBu3
R2
S SnBu3
R2
1
II.
Reaction Mechanisms
A.
Group Abstraction
Two mechanisms are considered to be reasonable possibilities for the carbon–sulfur bond
cleavage described by the reaction shown in eq 1.1 The first is the bimolecular, homolytic, substitution (SH2) reaction pictured in Scheme 2, and the second is a stepwise process that involves
formation of an intermediate (1) with a hypervalent sulfur atom (Scheme 3). The choice between
these two hinges on the existence of 1.
There is little experimental evidence upon which to base a decision about formation of a
compound with a hypervalent sulfur atom during carbon–sulfur bond cleavage, but reaction of the
thioacetal 2 with the tri-n-butyltin radical provides some suggestive information (Scheme 4).2
Although this reaction produces BuOCH2· (3), the effect of temperature on the ESR signal for this
radical is unexpected because the intensity of the signal increases as the temperature in the ESR
cavity rises. (Signals due to radicals arising from reaction of bromides with Bu3Sn· decrease with
rising temperature due to leveling of the Boltzmann distribution of spin states.2) A possible explanation for this behavior is that a slow, temperature-dependent reaction between the thioacetal 2 and
Bu3Sn· produces the hypervalent, sulfur-centered radical 4 (not observable by ESR), an intermediate that then fragments rapidly to give the ESR observable radical 3 (Scheme 4).2
64
Chapter 3
Scheme 4
Bu3Sn
BuOCH2SC6H5
2
BuOCH2
+
Bu3SnSC6H5
3
Bu3Sn
BuOCH2SC6H5
SnBu3
4
possible intermediate
Molecular orbital calculations also have been used to study the possibility of formation of
intermediates with hypervalent sulfur atoms. When these calculations focus on the reactions of
sulfides, they do not support the existence of such intermediates.1,3–6
Scheme 5
R
X + Sm III 2
R
- SmIIII 2
5
-X
radical
reactions
-X
R
X = SO2 Ar
+ Sm IIII 2
X
SmII I2
RSm IIII 2
R = a carbohydrate radical
Scheme 6
R
Bu3 Sn
- Bu3SnS-CARB
CARB SR
Bu3 Sn
- Bu3SnSR
CARB
CARB = a carbon-centered carbohydrate radical
R = CH3, CH3CH2, C6H5
B.
Electron-Transfer
Electron transfer to a sulfur-containing carbohydrate naturally depends upon such a compound having a group that readily accepts electrons. Sulfones meet this requirement and, thus, are
prime candidates for electron-transfer reaction.7 Two proposed mechanisms showing how such
transfer could lead to cleavage of a carbon–sulfur bond are shown in Scheme 5. In one of these a
sulfone reacts with an electron donor (e.g., SmI2) to produce a radical anion (5) that then fragments
Compounds With Carbon–Sulfur Single Bonds
65
to give an anion and a carbon-centered radical. In the other, dissociative electron transfer forms an
anion and a carbon-centered radical directly from reaction of a sulfone with SmI2.
III. Alkylthio and Arylthio Substituted Carbohydrates and Related Compounds
The identity of the carbon–sulfur single bond broken during reaction of a carbohydrate that
has two such bonds depends upon the stability of the carbon-centered radical being formed. If the
sulfur atom is part of a methylthio,8–11 ethylthio,12–15 or arylthio15–24 group, radical stability favors
producing a carbohydrate radical rather than a methyl, ethyl, phenyl, or p-tolyl radical (Scheme 6).
Scheme 7
BnO
CH2OBn
OR
BnO
Bu3 Sn
SMe
CH2OBn
OR
- Bu3 SnSMe
OH OBn
OH OBn
6
CH2OBn
Bu3SnH
- Bu3Sn
O
R =
OBn
OMe
CH2
OBn
CH2OBn
BnO
OR
H
OH OBn
A.
Simple Reduction
Since the ease of alkylthio and arylthio group abstraction correlates with the stability of the
carbon-centered radical produced, a radical stabilized by one or more oxygen atoms attached to the
radical center can be generated under relatively mild reaction conditions.8–11,16 The reaction pictured in Scheme 7 provides an example of the relation between radical stability and ease of radical
formation because the intermediate radical 6, with a stabilizing oxygen atom attached to the radical
center, forms upon heating of the corresponding methylthio glycoside with Bu3SnH for only 30
min at 110 oC.11 A noticeable feature of this reaction is the highly stereoselective hydrogen-atom
transfer to 6 attributable to the kinetic anomeric effect. (For a discussion of the kinetic anomeric
effect see Section III.B (page 255) of Chapter 13 in Volume I.)
It is reasonable to expect that if group abstraction cannot produce an oxygen-stabilized
radical, carbon–sulfur bond cleavage will require more vigorous reaction conditions. Experimental
findings support this expectation. The reaction shown in eq 2, which does not produce a stabilized
radical, requires heating at 100 oC over a period of 8-12 h to reach completion.18 Other transfor-
66
Chapter 3
mations of this type need similar14 or even longer reaction times19,21 or higher temperatures20 and
some do not occur at all.22 The shorter time (3 h) for the reaction shown in eq 323,24 may reflect a
relief of steric strain caused by the heavily substituted carbon atom adjacent to the reactive center.
BnO
CH2OBn
O OC6H5
OBn
CH2OBn
O OC6H5
BnO
AIBN
Bu3SnH
OBn
(2)
C6 H5 CH3
100 oC
SC6H5
OBn
BnO
76%
AIBN
Ar3 SnH
OR
O
AcHN
SC6H5
AcHN
O
Me2C
OR
(3)
OBn
BnO
97%
CH2
R=
CO2Me
O
C6 H5 CH3
110 oC
OBn
BnO
OBn
BnO
CO2Me
O
Ar = C6H5
O
O
O
R1OCH2
R1OCH2
B
S
H
AIBN
Bu3 SnH
X
C 6 H5 CH 3
80 oC
R 2O
CMe2
R1OCH2
SH
B
S
B
+
H
R 2O
35%
R 2O
H
(4)
H
48%
O
CH3
i-Pr2Si
NH
B=
R1, R2 =
N
B.
O
O
i-Pr2Si
S
X = OCOC6H5
Radical Cyclization
When alkylthio or arylthio group abstraction takes place from an unsaturated carbohydrate,
ring formation becomes a possibility; thus, cyclization follows loss of the phenylthio group from
compound 7 (Scheme 8).25 As with most cyclization reactions, ring formation is forced to compete
with hydrogen-atom abstraction. Favoring cyclization in the reaction shown in Scheme 8 is the
generally rapid formation of five-membered rings, but opposing it is the difficulty inherent in a
Compounds With Carbon–Sulfur Single Bonds
67
nucleophilic radical, such as 8, adding to a double bond that is not decidedly electron-deficient.
Successful cyclization in this situation requires suppressing hydrogen-atom abstraction by maintaining the concentration of the hydrogen-atom donor (Bu3SnH) at a low level during reaction.
Scheme 8
H
AcO
H
CH CH2
O
O
MeO
C 6H 5S
CH CH2
AcO
AcO
CH2
O
Bu3Sn
O
O
O
- Bu3SnSC6 H5
MeO
MeO
8
7
- Bu3Sn
Bu3SnH
AcO
AcO
CH2
O
O
CH3
O
Bu3SnH
- Bu3Sn
AcO
CH3
O
O
MeO
MeO
MeO
O
18%
74%
Scheme 9
CH2SSnBu3
CH2SSnBu3
S
O
OR
AcO
O
Bu3 Sn
Bu3SnH
HO
OR
OR - Bu Sn
3
H
H
H
AcO
CH3
O OR
R = C8H17
Bu3 SnH
- (Bu3 Sn)2S
AcO
AcO
CH2SSnBu3
O OR
AcO
AcO
80%
C.
Ring-Opening Reactions
Some reactive carbohydrates have a thioether linkage that is not part of an alkylthio or arylthio group.26–29 Reactions of these compounds usually,26–28 but not always,29 involve opening of a
ring that contains a sulfur atom. Some ring-opening reactions stop with formation of a thiol (eq
4),28 but others continue with the cleavage of the second carbon–sulfur bond (Scheme 9).27 The
reaction shown in eq 4 provides yet another example of the frequent competition between simple
68
Chapter 3
reduction and other radical reactions. In this case ring opening is minor when compared to simple
reduction.
Scheme 10
SEt
H
Bu3Sn
H
R
H
R
- Bu3SnSEt
SEt
Bu3SnH
SEt
- Bu3Sn
Bu3Sn
H
R
SEt
- Bu3SnSEt
H
H
R
Bu3SnH
H
H
R
- Bu3Sn
H
Scheme 11
O
Me2C
CO 2CH3
O
SEt
SEt
O
Me2C
Me2C
Bu3Sn
O
SEt
O
CH2CO 2CH3
O
SEt
O
CO 2CH3
- Bu3SnSEt
O
CMe2
O
O
O
CMe2
Me2C
Bu3SnH
O
CMe2
O
CO 2CH3
O
SEt
- Bu3Sn
O
O
CMe2
77%
IV. Dithioacetals
Dithioacetals react with tri-n-butyltin hydride to replace first one, and then the second, alkylthio group with a hydrogen atom (Scheme 10).30 Because the first group is replaced more rapidly
than the second, good yields of compounds with a single sulfur atom are obtained under the proper
reaction conditions.31–35 The greater reactivity of the first ethylthio group in these compounds is
due to formation of an intermediate, carbon-centered radical that is stabilized by the sulfur atom in
the remaining ethylthio group.
An unsaturated dithioacetal in which the double bond is properly positioned undergoes intramolecular radical addition.31–34 Reaction typically involves capture of the first-formed, carbon-centered radical by the multiple bond; thus, in the reaction shown in Scheme 11, the major
Compounds With Carbon–Sulfur Single Bonds
69
product has a new ring system with an ethylthio substituent.31 Here again the greater reactivity of
the first ethylthio group allows reaction to occur with no detectable loss of the second.
ROCH2
O
B
ROCH2
O
AIBN
Bu3 SnH
C6 H5 CH3
110 oC
(5)
CH3
CH2SCOC6H5
O
95%
O
R = Si(C6H5) 2t -Bu
B
NH
B=
N
O
Scheme 12
O
O
MeSCS
CH2SnBu3
MeSCS
O
OMe
OBn
BnO
O
Bu3Sn
OBn
- Bu3Sn
OBn
OMe
OBn
BnO
10
9
CH2SnBu3
O
- MeSCS
O
OBn
OMe
OBn
BnO
11
V.
Thiocarbonates and Dithiocarbonates
Thiocarbonates and dithiocarbonates are compounds in which at least one sulfur atom is
bonded to the carbon atom of a carbonyl group. The reactivity of these compounds is similar to that
of the sulfur-containing compounds already discussed in that reaction begins with carbon–sulfur
bond cleavage producing the more stable of the possible carbon-centered radicals; thus, in the
reaction shown in eq 5, product identity is consistent with forming an intermediate allylic radical
from reaction of a thiocarbonate.36
Addition of Bu3Sn· to the dithiocarbonate 9 is the first step in an addition-elimination reaction that produces the tin-containing compound 11 (Scheme 12).37 The stability of CH3SC(=O)S·
70
Chapter 3
is critical to this type of reaction because it, rather than Bu3Sn·, is expelled when a radical such as
10 forms a tin-containing product.37,38 Since Bu3Sn· addition to a double bond often is reversible,
10 sometimes may break a carbon–tin bond causing an undetectable regeneration of Bu3Sn· and
the substrate 9.
S
N
N
O SEt
CO
CH3
O SEt
Bu3 SnH
C6 H5 CH3
110 oC
OBz
BzO
(6)
CH3
BzO
OBz
86%
12
Scheme 13
Cl
N
ROCH2
O
C6H5OCO
N
S
N
Cl
Bu3Sn
R = SiMe2t-Bu
ROCH2
O
S
N
C6H5OCO
SSnBu3
S
O
- C6 H5 OCSSnBu 3
H
Cl
N
N
S
N
ROCH2
O
Cl
Bu3 SnH
N
S
ROCH2
O
N
ROCH2
O
S
N
- Bu3Sn
VI. O-Thiocarbonyl Compounds
Compounds with carbon–sulfur single bonds are substantially less reactive with tin- and
silicon-centered radicals than are compounds with C–S double bonds. Among carbohydrates these
double bonds are almost always part of O-thiocarbonyl groups. (The reactions of O-thiocarbonyl
carbohydrate derivatives are discussed in Chapter 12.) The reaction shown in eq 6 illustrates the
greater reactivity of a C–S double bond when compared to a C–S single bond because only the
O-thiocarbonyl group in the 1-thioglycoside 12 reacts even though an ethylthio group is present in
the molecule.39 Greater reactivity of a carbon–sulfur double bond also can be seen in the reaction
shown in Scheme 13, where Bu3Sn· reacts only with the O-thiocarbonyl group.26 A quantitative
measure of the reactivity of C–S single and double bonds comes from comparing absolute rate
constants for their reactions; thus, rate constants for reaction of (Me3Si)3Si· with C10H21SC6H5 and
Compounds With Carbon–Sulfur Single Bonds
71
C6H11OC(=S)SMe are less than 5 x 106 and 1.1 x 109 M-1s-1, respectively, at 21 oC.40 The reactions
in Schemes 12 and 13 also illustrate the ease of fragmentation of a carbon–sulfur single bond when
a radical is centered on an adjacent carbon atom.
VII. Sulfones
Radicals are involved in both the synthesis and the reactions of carbohydrate sulfones. Sulfones produce carbon-centered radicals by group abstraction, dissociative electron-transfer, and
photochemical bond homolysis. Sulfone synthesis takes place when a sulfonyl radical adds to an
unsaturated carbohydrate.
R
R
SO2C6H5
O OBn
I
+
O OBn
h
Bu6 Sn 2
(7)
THF
O
O
CMe2
O
CMe2
O
CH3
74%
R = CH3
OTBS
CH2OBn
CH2OBn
O
OBn
SO2C6 H5
BnO
AIBN
Bu3SnH
C6 H5 CH3
110 oC
O
OBn
SnBu3
(8)
BnO
77%
A.
Addition-Elimination Reactions
Addition of a carbohydrate radical to an allylic41 or vinylic42 sulfone is the first step in a reaction that forms a new carbon–carbon bond and expels an arylsulfonyl radical. The reaction shown
in eq 7 uses this addition-elimination process to attach a six-carbon-atom chain to a pyranoid
ring.41 Addition-elimination reaction also can replace an arylsulfonyl group in an unsaturated
sulfone with a tri-n-butyltin group (eq 843).43–47 A basic difference in these two reactions is the
location of the double bond in the product. When an allylic sulfone reacts (eq 7), the double bond
shifts to a new position, but reaction of a vinylic sulfone returns the double bond to its original
place (eq 8).
72
Chapter 3
Scheme 14
radical phase
BnOCH2 OMe
O
BnO
BnO
BnOCH2 OMe
O
BnO
BnO
SmI2
- SmI2
SO2Ar
SO2 Ar
Ar = C6H5
- ArSO2
BnOCH2
BnO
BnO
OMe
O
13
SmI2
BnOCH2 OMe
O
BnO
BnO
SmI2
nonradical phase
O
CH2OBn
O
OBn
- SmI2(OMe)
BnO
9%
B.
Electron-Transfer Reactions
1.
Samarium(II) Iodide
13
product yields after
treatment with NH4Cl
and chromatographic
purification
BnOCH2 OMe
O
BnO
BnO
OH
78%
Electron transfer from SmI2 to a glycosyl aryl sulfone generates a pyranos-1-yl radical. The
options for reactions of this radical are limited either to combination with a second molecule of
SmI2 or to radical reaction that is fast enough to occur before combination can take place. Combination of pyranos-1-yl radicals with SmI2 produces organosamarium intermediates that undergo
typical reactions of organometallic compounds. These reactions include addition to aldehydes and
ketones,48–57 proton abstraction,7,58 and β-elimination.7,56–58
a.
Reactions of Organosamarium Compounds
(1). Addition to Carbonyl Compounds
Addition to an aldehyde or ketone is a common reaction for an organosamarium compound
generated from a pyranos-1-yl radical. Formation of the organometallic intermediate takes place
during the radical phase of such a reaction while addition of this organosamarium compound to an
Compounds With Carbon–Sulfur Single Bonds
73
aldehyde or ketone occurs during the nonradical portion of the process (Scheme 14).48 In most
such reactions the addition is to a simple carbonyl compound such as cyclohexanone,48,49,51–57 but
sometimes it is to an aldehydo group in a carbohydrate.50,52,57 Addition reactions of the type shown
in Scheme 14 are usually accompanied by β elimination to form glycals.55 At least in some
instances, addition of small amounts of nickel(II) iodide to a reaction mixture can decrease glycal
formation in favor of an increase in the yield of addition products.51
Scheme 15
ROCH2
ROCH2
O SO2C6H5
OR
SmI2
- C 6 H 5 SO 2 SmI2
O
OR
(HMPA must
be present)
RO
RO
OR
OR
SmI2
O
O
SmI2
SmI2
OR
OR
- ROSmI2
H 2 O(trace)
- HOSmI2
ROCH2
ROCH2
OH
O
OR
OR
RO
H
OR
RO
98%
R = OAc
0%
56%
R = OBn
33%
not
reported
R = OBn
(more H2O
present)
77%
(2). β-Elimination and Proton-Transfer Reactions
Elimination to give a glycal occurs as a side reaction when a glycosyl phenyl sulfone reacts
with SmI2 in the presence of an aldehyde or ketone, but elimination can be the major reaction
pathway, when carbonyl compounds are absent. The amount of glycal formed in a reaction depends upon how easily a C-2 substituent can depart as an anion. A carbohydrate with an O-acetyl
74
Chapter 3
group at C-2 gives a far higher yield of glycal than does one with an O-benzyl group at this
position (Scheme 15).7,49 A process competing with elimination is proton abstraction from a donor
(presumably water) present in the reaction mixture. The O-acetyl group is so effective as a leaving
group that proton transfer from H2O to the organosamarium compound is inconsequential, but for
the less effective O-benzyl leaving group proton transfer is significant. Proton transfer actually
becomes the major reaction pathway when greater than a trace amount of water is present in the
reaction mixture. The data given in Scheme 15 show how the balance between β-elimination and
proton abstraction changes as reaction conditions and substrate structure change.7,49
Scheme 16
BnOCH2
O SO 2 Ar
OBn
SmI2
- C6 H5 SO 2 SmI2
O
SmI2
O
SmI2
(HMPA must
be present)
BnO
O
O
O
14
15
BnOCH2
O
OBn
HX
O
SmI2
O
- XSmI2
BnO
O
CH3
O
CH2SmI2
O
CH2
78%
HX = a proton donor
b.
Ar = C6H5
Radical Cyclization
Cyclization of some radicals is fast enough to prevent combination with SmI2 from occurring
prior to ring formation.59–63 The unsaturated glycosyl phenyl sulfone 14, for example, forms a new
ring even though combination of the intermediate radical 15 with SmI2 potentially could suppress
this reaction (Scheme 16).62 HMPA is critical to the reaction shown in Scheme 16 because it
promotes electron transfer by reducing the energy required for electron donation from the highest
occupied molecular orbital (HOMO) of SmI2 to the lowest unoccupied molecular orbital (LUMO)
of the sulfone (Figure 1).60 The effect of HMPA is so great that in its absence phenyl sulfones do
not react with SmI2.60
HMPA is not required for reaction of 2-pyridyl sulfones due to the effect of the 2-pyridyl
group on sulfone MO energy levels. Because the LUMO energy of a 2-pyridyl sulfone is lower
than that of a phenyl sulfone, transfer of an electron to the 2-pyridyl derivative occurs more easily
than transfer to the corresponding phenyl sulfone (Figure 2); as a result, ring formation from a
2-pyridyl sulfone can take place without HMPA assisting electron transfer (Scheme 17).60
Compounds With Carbon–Sulfur Single Bonds
75

SO
SO 2C6H5
(LUMO)
potential
energy
(HOMO)
SmI2
sulfone
(HOMO)
SmI2
(HMPA)
sulfone
2C 6H 5
(LUMO)
Figure1. Effect of HMPA on the HOMO energy of the SmI2
SO 2C6H5
(LUMO)
potential
energy
SO 2C5H4N
(LUMO)
sulfone
(HOMO)
SmI2
(HOMO)
SmI2
sulfone
Figure 2. Difference in LUMO () energy levels
between phenyl and 2-pyridyl sulfones
Scheme 17
O Si
BnOCH2
BnO
BnO
O
SmI2
(no HMPA)
O
Si
O
THF
20 oC
SO2
protonation
and desilylation
N
OH
BnOCH2
BnO
BnO
O
CH2CH3
80%
CH2SmI2
76
Chapter 3
Scheme 18
CH2OAc
CH2OAc
O SO 2 Ar
OAc
- SmI2
- ArSO2
AcO
O
SmI2
OAc
AcO
CH2OAc
O
SmI2
OAc
SmI2
OAc
AcO
OAc
OAc
17
16
- SmI2(OAc)
17
Ar =
18
N
CH2OAc

and 
dimers
O
OAc
AcO
19
c.
no HMPA
0%
92%
slow addition of HMPA
(8 equiv) during reaction
0%
96%
HMPA (8 equiv) present at
the beginning of the reaction
52%
40%
Radical Dimerization
When the 2-pyridylsulfone 16 reacts with SmI2 (no HMPA present), the glycal 18 forms in
high yield (Scheme 18).64 Adding HMPA slowly to the reaction mixture over a period of two hours
has little effect on the glycal yield, but if the same amount of HMPA is present at the beginning of
the reaction, glycal yield decreases and the three possible dimers formed from the pyranos-1-yl
radical 17 become (in combination) the major product (Scheme 18). Formation of these dimers
indicates that HMPA accelerates the production of 17 but not its reaction with SmI2. When HMPA
is present at the beginning of the reaction, the concentration of 17 quickly builds to the point that
its dimerization takes place more rapidly than its reaction with SmI2.64 {Radical formation from
glycosyl bromides [Chapter 2, Section II.G.1 (p 43)] and glycosyl phenyl selenides [Chapter 15,
Section II.B.6 (p 95)] under the proper conditions gives dimers similar to those shown in Scheme
18.}
Photolysis of glycosyl phenyl sulfones is another way for producing pyranos-1-yl radicals
that dimerize.65 The product mixture from such a reaction is more complex and the dimer yield
lower than that from the reaction with SmI2 shown in Scheme 18 (HMPA present at the beginning
of the reaction). The ratios of the three stereoisomeric dimers in photochemical and SmI2 reactions
are quite similar, a fact considered to be a “stereochemical signature” for pyranos-1-yl radical
dimerization.64
Compounds With Carbon–Sulfur Single Bonds
2.
77
Chromium(II) Complexes
Chromium(II) complexes also can function as electron donors in reactions of carbohydrate
sulfones,66 but such reactions are far less common than those in which SmI2 is the electron donor.
The radical produced by electron transfer from [Cr(II)(EDTA)]2- has the same types of options
available as a radical generated by electron transfer from SmI2; that is, the radical either can
combine with another chromium(II) complex or undergo a radical reaction that is fast enough to
compete with the combination process (Scheme 19). One reaction that is sufficiently rapid is
radical addition to a compound with an electron-deficient double bond (eq 9).66
Scheme 19
CH2OAc
CH2OAc
O SO 2 Ar
2-
Cr II (EDTA)
OAc
- Cr III X(EDTA)
AcO
O
radical
reaction
OAc
2-
AcO
OAc
OAc
X = ArSO2
Cr II(EDTA)
CH2OAc
O
CH2OAc
- Cr III (OAc)(EDTA)
OAc
2-
2-
AcO
O
CrIII(EDTA)2-
OAc
AcO
OAc
CO2
EDTA =
CO2
NCH2CH2N
Ar = C6H5
CO2
CO2
AcOCH2
AcOCH2
OAc
O SO 2 Ar
+ CH2=CHCN
AcO
OAc
N
Ar =
S
Cr II (EDTA)
H2O, DMF
2-
O
OAc
AcO
(9)
CH2CH2CN
OAc
40%
78
C.
Chapter 3
Sulfone Synthesis
p-Tolylsulfonyl radicals add reversibly to carbon–carbon multiple bonds. If the adduct radical is “captured” before addition is reversed, the resulting product is a sulfone.67–69 Radical cyclization, such as that shown in Scheme 20,68 is rapid enough to trap the intermediate radical 16. As
long as the new ring remains intact, loss of the p-tolylsulfonyl group will not take place, insuring
completion of sulfone formation.
Scheme 20
ArSO 2 Br
h
ArSO 2
+ Br
CH2OAc
O
O
ArSO2
O
AcO
CH2OAc
- ArSO2
O
AcO
ArSO2
16
Ar = C6H4CH3 (p)
CH2OAc
O
O
ArSO2Br
Br
O
AcO
CH 2OAc
- ArSO2
O
AcO
ArSO 2CH2
ArSO 2CH 2
O
O
+
SH
R
+
RH
( 10 )
S
R = a carbon-centered radical
VIII.Thiols and Thiyl Radicals
In compounds with an H–S bond, hydrogen-atom abstraction to produce a sulfur-centered
radical (eq 10) is a significant (sometimes the exclusive) reaction pathway. Such reactivity exists
because thiols are among the most effective hydrogen-atom donors in organic chemistry. Rate
Compounds With Carbon–Sulfur Single Bonds
79
constants for hydrogen-atom abstraction by primary, secondary, and tertiary, carbon-centered
radicals from thiophenol range from 0.8 x 108 to 1.5 x 108 M-1s-1 at 25 oC.70
Scheme 21
CH2OAc
overall reaction
O
CH2OAc
OAc
O
O
OAc
+
SH
OAc
AcO
OAc
OMe
AcO
h
DPAP
CH2Cl 2
S
OAc
AcO
O
OAc
OAc
20
21
OMe
AcO
OAc
O
DPAP = (CH3O)2CCC6H5
22
C6H5
propagation steps
O
O
S
OAc
23
AcO
OAc
21
AcO
O
O
O
S
OAc
+
OAc
AcO
S
OAc
OAc
+
SH
OAc
20
O
S
OAc
+
OAc
AcO
S
OAc
23
22
A characteristic reaction of a thiyl radical is addition to a carbon–carbon multiple bond.71–85
In the reaction shown in Scheme 21, for example, addition of the thiyl radical 23 to the unsaturated
carbohydrate 21 leads to formation of the S-disaccharide 22.77 This reaction is not only regiospecific but hydrogen-atom abstraction from 20 is so much faster than reaction with the molecular
oxygen dissolved in the reaction mixture that an inert atmosphere is not required for successful
S-disaccharide formation. Similar radical addition takes place between the thiol 20 and various
78
D-glycals, including the D-glucal 24 (eq 11).
80
Chapter 3
Even though the most common radical reaction of a compound with an H–S bond is
hydrogen-atom abstraction, under some conditions the HS group is replaced by a hydrogen atom
(eq 12).86
Although a carbohydrate containing a sulfur-centered radical typically is generated by
hydrogen-atom abstraction from a thiol, the reaction shown in eq 13 forms a thiyl radical by the
addition-elimination sequence pictured in Scheme 22.87 Critical to chain propagation in this
reaction is the removal of the sulfur atom from 25 by reaction with triphenylphosphine.
CH2OAc
CH2OAc
O
CH2OAc
O
OAc
+ RSH
h
DPAP
AcO
O
OAc SR
AcO
AcO
SR
46%
34%
AcOCH2
O
O
R=
( 11 )
OAc
+
OAc
DPAP = (CH3O)2CCC6H5
C6H5
AcO
OAc
CH2OAc
OH
CH2OAc
O SH
OAc
+ Ar3SiH
H
OAc
AcO
RN=NR
dioxane
60 oC
OAc
( 12 )
H
OAc
AcO
Ar = C6H5 R = t-BuO
91%
AcOCH2
AcOCH2
O
OAc
AcO
AcO
+ Ar3SiSH
CO2Et
S
(C 6 H5 ) 3 P
(CH3 ) 3 COOC(CH3 ) 3
CH3 (CH 2 ) 6 CH3

AcO
O
OAc
AcO
( 13 )
CO2Et
IX. Summary
Tin-centered radicals react with carbohydrates that contain methylthio, ethylthio, or phenylthio groups to produce carbon-centered radicals. Two mechanisms have been proposed for such
a reaction. The first is a concerted SH2 process, and the second is a stepwise reaction that forms an
Compounds With Carbon–Sulfur Single Bonds
81
intermediate with a hypervalent sulfur atom. Molecular orbital calculations favor the concerted
process.
Scheme 22
CO2Et
SR
S P(C6H5)3
R
AcOCH2
O
CO2Et
RSP(C6H5)3
R
SR
25
OAc
AcO
AcO
CO2Et
RS
P(C6H5)3
R=
R
Compounds with alkylthio or arylthio groups break the C–S bond that produces the more
stable, carbon-centered radical. This means that when fragmentation takes place in a carbohydrate
containing a methylthio, ethylthio, or phenylthio substituent, a carbohydrate radical forms rather
than an alkyl or aryl radical. Reactions that begin with carbon–sulfur bond cleavage often lead to
either simple reduction or radical cyclization. Similar reactions occur when the sulfur atom is part
of a dithioacetal, thiocarbonate, or dithiocarbonate.
When the carbon–sulfur bonds in a carbohydrate are part of a sulfone and when an electron-donor (usually SmI2) is present, bond cleavage occurs via an electron-transfer reaction. The
resulting radical combines rapidly with a second molecule of SmI2 to produce an organosamarium
intermediate that undergoes reactions typical of an organometallic compound (e.g., proton abstraction, β elimination, or addition to an aldehyde or ketone). Radical cyclization is one of the few
reactions fast enough to occur before this combination takes place.
If a compound has a hydrogen–sulfur bond, the major reaction pathway usually is
hydrogen-atom abstraction to form a sulfur-centered radical. This radical adds readily to a carbon–
carbon double bond.
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