Stereochemistry of the Vinylic SRN1 Reaction of Triarylvinyl Halides. the Structure of the Intermediate α-Arylvinyl Radical

Article abstract of DOI:10.1021/jo961007v

Evidence for the intermediacy of a vinyl radical in the vinylic S_RN1 reaction (S_RN1(V)) of 2-anisyl-1,2-diphenylvinyl bromide 2 is obtained. The photostimulated SRN!(V) reaction of pinacolone enolate ion with (E)-2 and (Z)-2, which are used as stereoindicators, gives complete loss of the original stereochemistry of the two precursors in the substituted and hydrodehalogenated products; i.e., stereoconvergence is found. It is concluded that in the reaction of 2 a -substituted a-phenylvinyl radical is a reactive intermediate and that it has either a linear structure or an average linear structure due to a rapidly interconverting E,Z mixture of bent radicals. This conclusion is supported by comparing the stereochemical course of the S_RN1(V) reaction with those of other reactions of the same precursor, which unambiguously give rise to the same α-phenylvinyl radical intermediate by alternative mechanisms. Among the reactions investigated, the hydrodehalogenation of precursor 2 by LAH appears to take place by an ET mechanism.

Full text of DOI:10.1021/jo961007v

8
878
J . Org. Chem. 1996, 61, 8878-8884
Ster eoch em istr y of th e Vin ylic SRN1 Rea ction of Tr ia r ylvin yl
Ha lid es. Th e Str u ctu r e of th e In ter m ed ia te r-Ar ylvin yl Ra d ica l
Carlo Galli,* Patrizia Gentili, Alessandra Guarnieri, and Zvi Rappoport*,†
Dipartimento di Chimica, Centro CNR Meccanismi di Reazione, Universit a` “La Sapienza”, 00185 Roma,
Italy, and Department of Organic Chemistry, The Hebrew University, J erusalem 91904, Israel
Received May 30, 1996X
Evidence for the intermediacy of a vinyl radical in the vinylic SRN1 reaction (SRN1(V)) of 2-anisyl-
1
,2-diphenylvinyl bromide 2 is obtained. The photostimulated SRN1(V) reaction of pinacolone enolate
ion with (E)-2 and (Z)-2, which are used as stereoindicators, gives complete loss of the original
stereochemistry of the two precursors in the substituted and hydrodehalogenated products; i.e.,
stereoconvergence is found. It is concluded that in the reaction of 2 a â-substituted R-phenylvinyl
radical is a reactive intermediate and that it has either a linear structure or an average linear
structure due to a rapidly interconverting E,Z mixture of bent radicals. This conclusion is supported
by comparing the stereochemical course of the SRN1(V) reaction with those of other reactions of the
same precursor, which unambiguously give rise to the same R-phenylvinyl radical intermediate by
alternative mechanisms. Among the reactions investigated, the hydrodehalogenation of precursor
2
by LAH appears to take place by an ET mechanism.
Nucleophilic substitution reactions of aryl halides via
of the vinyl radical, viz. the vinyl anion and the vinyl
cation, are bent and configurationally stable for the
former,6 while linear (or bridged) for the latter, an
intermediate situation for the vinyl radical is expected.
In fact, the parent vinyl radical is suggested to be a
the free radical chain SRN1 mechanism proceed by the
1
7
intermediacy of the aryl radical. Vinyl halides, showing
8
,9
many reactivity features in common with aryl halides,
2
were recently found to react by a comparable substitu-
tion mechanism (Scheme 1, where RX is the aryl or vinyl
Sch em e 1
hν/Y-
•
-
RX
8 RX (initiation)
(1)
(2)
(3)
(4)
RX•-
9
8 R + X
•
-
bent species, which rapidly inverts on the ESR time scale
1
0
owing to a low barrier to inversion (ca. 3 kcal/mol). The
linear structure represents the “transition state” for this
inversion.
•
-
•-
R + Y
9
8 RY
RY•- + RX
98 RY + RX
•-
-
substrate, and Y is a suitable nucleophile). The occur-
rence of the vinylic SRN1 reaction (hereafter, SRN1(V))
appears to be strongly dependent on specific structural
features of the vinyl halide,2 which may prevent or
minimize competition from alternative ionic processes3
However, R-substituents can modify this situation to
•
a major extent. For example, the R CdC(R′) radical,
2
1
1
(e.g., elimination-addition). So far, our investigation in
where R′ ) Ph, appears linear by ESR investigation,
whereas in the case of R′ ) Cl or Br there is evidence in
this field has mainly focused on the effect of the structure
of the substrate, in particular the role of certain substit-
uents.4 Questions about the stereochemical course of the
(6) See: (a) Miller, S. I.; Lee, W. G. J . Am. Chem. Soc. 1959, 81,
S
RN1(V) reaction, strictly related to the structure of the
6313. (b) Walborsky, H. M.; Turner, L. M. Ibid. 1972, 94, 2273. (c)
Corey, E. J .; Ulrich, P.; Fitzpatrick, J . M. Ibid. 1976, 98, 222. (d)
Froelicher, S. W.; Freiser, B. S.; Squires, R. R. Ibid. 1986, 108, 2853.
Here, an E f Z isomerization barrier of 26.6 kcal/mol for 1-propenyl
anions is calculated. (e) Chou, P. K.; Kass, S. R. ibid. 1991, 113, 4357.
vinyl radical intermediate, were not addressed.
Conceivable alternatives for the structure of vinyl
2
5
radicals are an sp bent geometry or an sp linear one. If
we remember that the structures of the “close neighbors”
(7) (a) Mayr, H.; Schneider, R.; Wilhelm, D.; Schleyer, P. v. R. J .
Org. Chem. 1981, 46, 5336. (b) Rappoport, Z. In Reactive Intermediates;
Abramovitch, R. A., Ed.; Plenum Press: New York, 1983; Vol. 3, pp
427-615. (c) Berkowitz, J .; Mayhew, C. A.; Ruscic, B. J . Chem. Phys.
1988, 88, 7397. (d) Lindh, R.; Rice, J . E.; Lee, T. J . Ibid. 1991, 94,
8008.
†
The Hebrew University.
Abstract published in Advance ACS Abstracts, November 1, 1996.
X
(1) (a) Bunnett, J . F. Acc. Chem. Res. 1978, 11, 413. (b) Rossi, R. A.;
De Rossi, R. H. Aromatic Substitution by the SRN1 Mechanism; ACS
Monograph 178; American Chemical Society: Washington, DC, 1983.
(8) J enkins, P. R.; Symons, M. C. R.; Booth, S. E.; Swain, C. J .
Tetrahedron Lett. 1992, 33, 3543.
(
c) Rossi, R. A.; Pierini, A. B.; Pe n˜ e´ n˜ ory, A. B. In The Chemistry of
(9) Gillespie, R. J . Chem. Soc. Rev. 1992, 21, 59.
Functional Groups. Supplement D2: The Chemistry of Halides, Pseudo-
halides and Azides; Patai, S., Rappoport, Z., Eds.; Wiley: Chichester,
1
(10) (a) Fessenden, R. W.; Schuler, R. H. J . Chem. Phys. 1963, 39,
2147. (b) Cochran, E. L.; Adrian, F. J .; Bowers, V. A. Ibid. 1964, 40,
213. (c) Fessenden, R. W. Ibid. 1967, 71, 74.
995; Chapter 24.
(
(
(
2) Galli, C.; Gentili, P.; Rappoport, Z. J . Org. Chem. 1994, 59, 6786.
3) Rappoport, Z. Recl. Trav. Chim. Pays-Bas 1985, 104, 309.
4) Amatore, C.; Galli, C.; Gentili, P.; Guarnieri, A.; Schottland, E.;
(11) (a) Bonazzola, L.; Feinstein, S.; Marx, R. Mol. Phys. 1971, 22,
689. (b) Neilson, G. W.; Symons, M. C. R. J . Chem. Soc., Perkin Trans.
2 1973, 1405. (c) Kasai, P. H.; Whipple, E. B. J . Am. Chem. Soc. 1967,
89, 1033. (d) Bennett, J . E.; Howard, J . A. Chem. Phys. Lett. 1971, 9,
460. (e) Panek, E. J .; Kaiser, L. R.; Whiteside, G. M. J . Am. Chem.
Soc. 1977, 99, 3708.
Rappoport, Z. J . Chem. Soc., Perkin Trans. 2 1995, 2341.
5) (a) Simamura, O. Top. Stereochem. 1969, 4, 1. (b) Bentrude, W.
G. Ann. Rev. Phys. Chem. 1967, 18, 300.
(
S0022-3263(96)01007-9 CCC: $12.00 © 1996 American Chemical Society

Vinylic SRNV Reaction of Triarylvinyl Halides
J . Org. Chem., Vol. 61, No. 25, 1996 8879
favor of a bent stable structure.12 Finally, a halogen-
bridged structure, analogous to an iodine-bridged vinyl
cation intermediate that accounted for the stereochem-
istry of its capture, has been suggested for a â-halogen-
substituted vinyl radical.14 The structure of vinyl radi-
cals thus appears wavering.
addition-elimination routes, respectively,2,4 and it there-
fore fulfills the indicated prerequisites for being an SRN1-
(V) substrate. To our surprise, the structurally similar
compounds 3 (86:14 (Z)-3:(E)-3) and 4 (91:9 (E)-4:(Z)-4)
did not lend themselves to the photostimulated SRN1(V)
reaction with a ketone enolate ion (see below).
1
3
The structure of the vinyl radical is expected to affect
the stereochemistry of the products: if it is bridged or
bent and configurationally stable, the reaction products
will retain the original configuration of the precursor.13
Alternatively, a linear species should give a mixture of
retained and inverted products in ratios depending on
the relative steric hindrance of the â-substituents. Fi-
nally, if it is bent and inverting, the stereochemistry will
be determined by the relative rates of inversion and
capture (vide infra), but again a mixture of isomers is
expected.5
Determination of the reduction potential of 1, (Z)-2,
mostly (Z)-3, and mostly (E)-4 gives the very comparable
values of -1.86,2 -1.92, -2.00, and -2.08 V (vs. SCE,
in THF), respectively. These similar electron affinities
would be expected to allow a comparable efficiency in the
initiation of the SRN1(V) reaction chain of these precur-
sors. Lack of SRN1(V) reactivity with 3 and 4 is possibly
due to the presence of the R-anisyl group that, at variance
,4
,15
An investigation on the stereochemical outcome of a
S
RN1(V) reaction was initiated, aimed to characterize the
2
vinyl radical intermediate. To this end, an appropriate
with the â-anisyl group of 2, may allow incursion of an
ionic vinylic S
N
1 route.3
,18-20
Further investigation is in
pair of E/ Z isomeric precursors was selected, and their
behavior was tested under the typical conditions of SRN
1
progress along this line, but it has deferred a more
extensive use of 3 and 4 in the present study. Once more,
we find that the window of occurrence of the SRN1(V)
route is narrow, as structurally similar compounds do
not behave in the same way.
nucleophilic processes. The results are reported here and
compared with the stereochemical outcome of other
exemplary reactions of the same precursor, expected to
occur by the same vinyl radical intermediate generated
by alternative mechanisms.
4
The photostimulated substitution reaction of (E)-2 and
-
(
Z)-2 with the enolate ion of pinacolone ( CH
2
COCMe
3
;
5
) was investigated in Me
2
SO solution at room temper-
ature in separate experiments. The substitution product
and the hydrodehalogenation product 7 were obtained
Resu lts a n d Discu ssion
2
Th e SRN1(V) Rea ction . For the purpose of our
stereochemical investigation, there are two prerequisites
for the substituents on the vinyl halide. First, the system
should be as close as possible to that of 1-bromo-1,2,2-
triphenylethene (1), which was shown to react via the
6
in ca. 40% and 5% yields, respectively, after 20 min
reaction time (Table 1). Both products were E,Z-pairs,
as easily detected by GC and GC-MS analysis. Product
6
was independently prepared as an E,Z-pair and char-
S
RN1(V) route without intervention from competing ionic
acterized, while (E)-7 and (Z)-7 were synthesized accord-
ing to the literature. Under the above reaction condi-
tions, ca. 50% of the precursor was recovered unreacted.
The important mechanistic point is that the E,Z mixtures
of products 6 and 7 have the same composition (within
2
routes. Second, a pair of configurationally pure E and
Z isomers, which are stable to mutual isomerization
under the reaction conditions by routes that are ir-
relevant to the substitution, should be prepared. After
preliminary screening, 2, differing from 1 by the replace-
ment of one â-Ph by a â-anisyl (An) group, was found as
a proper substrate.
16
2
3
2
%) on starting either from (E)-2 or from (Z)-2 (Scheme
); i.e., the stereochemical outcome is complete stereo-
convergence.
When the photostimulated reaction was repeated in
the presence of the electron scavenger p-dinitrobenzene,
no conversion to products was obtained, indicating that
electron-transfer steps must play an important role in
the process. The stability of the precursors under the
adopted photostimulation conditions was investigated
with the more largely available (Z)-2, and the result is
taken to hold for (E)-2 as well, due to the close similarity
of the two isomeric precursors. After irradiation at a
wavelength of 350 nm, at which the substitution took
place, but in the absence of enolate ion 5, (Z)-2 was
Compound 2, which was previously prepared and
separated into E and Z isomers,1
6,17
was already inves-
tigated as a stereomodel for the vinylic S
N
1 reaction3
,18
1
7
under stringent conditions. It lacks vinylic or allylic
C-H bonds or electron-withdrawing substituents, which
can lead to substitution by elimination-addition and
recovered unchanged. Thus, neither direct photoin-
duced1
9,21
isomerization nor cleavage-isomerization-
(12) (a) Liu, M. S.; Soloway, S.; Wedegaertner, D. K.; Kampmeier,
21
recombination of the vinyl halide (VyX in Scheme 3),
whereby the original configuration of the reagent would
be lost, take place. Configuration of the latter must be
lost only during the substitution process.
J . A. J . Am. Chem. Soc. 1971, 93, 3809. (b) Singer, L. A.; Kong, N. P.
Tetrahedron Lett. 1967, 643.
(
13) Bassi, P.; Tonellato, U. Gazz. Chim. Ital. 1972, 102, 387; J .
Chem. Soc., Perkin Trans. 2 1974, 1283.
14) (a) Skell, P. S.; Allen, R. G. J . Am. Chem. Soc. 1964, 86, 1559.
b) Abell, P. I.; Piette, L. H. Ibid. 1962, 84, 916.
15) (a) Kampmeier, J . A.; Fantazier, R. M. J . Am. Chem. Soc. 1966,
8, 1959. (b) Singer, L. A.; Kong, N. P. Ibid. 1966, 88, 5213.
16) Curtin, D. Y.; Harris, E. E.; Meislich, E. K. J . Am. Chem. Soc.
952, 74, 2901.
17) Rappoport, Z.; Houminer, Y. J . Chem. Soc., Perkin Trans. 2
973, 1506.
18) Stang, P. J .; Rappoport, Z.; Hanack, M.; Subramanian, L. R.
Vinyl Cations; Academic Press: New York, 1979.
(
(
(
(19) Lodder, G.; Cornelisse, J . In The Chemistry of Functional
Groups. Supplement D2: The Chemistry of Halides, Pseudo-halides and
Azides; Patai, S., Rappoport, Z., Eds.; Wiley: Chichester, 1995; Chapter
16.
(20) Hori, K.; Kamada, H.; Kitamura, T.; Kobayashi, S.; Taniguchi,
H. J . Chem. Soc., Perkin Trans. 2 1992, 871.
8
1
1
(
(
(
(21) Walling, C. In Molecular Rearrangements; De Mayo, P., Ed.;
Wiley-Interscience: New York, 1963; Vol. 1, Chapter 7.

8
880 J . Org. Chem., Vol. 61, No. 25, 1996
Galli et al.
Ta ble 1. Yield s a n d Ster eoch em ica l Ou tcom e of th e Rea ction s In vestiga ted
reaction
substrate
VyX)
(
time (min)
% VyX left
% products (stereochem composn)
(
a) Photostimulated SRN1(V) with 5 in Me2SO at rta
(
(
(
(
E)-2
E)-2
Z)-2
Z)-2
20
20
20
10
47 ((E)-2)
51 ((E)-2)
45 ((Z)-2)
61 ((Z)-2)
38 ((E)-6:(Z)-6 ) 52:48)
((E)-7:(Z)-7 ) 55:45)
40 ((E)-6:(Z)-6 ) 53:47)
((E)-7:(Z)-7 ) 57:43)
39 ((E)-6:(Z)-6 ) 55:45)
((E)-7:(Z)-7 ) 56:44)
21 ((E)-6:(Z)-6 ) 51:49)
((E)-7:(Z)-7 ) 55:45)
4
7
5
2
b
c
(Z)-2
Z)-2
20
20
90 ((Z)-2)
98 ((Z)-2)
(
(
b) Hydrodehalogenation with Bu3SnH/AIBN in Refluxing Benzened
(
(
(
3
4
E)-2
Z)-2
Z)-2
(86% (Z)-3)
(91% (E)-4)
300
360
360
360
360
32 ((E)-2)
62 ((E)-7:(Z)-7 ) 56:44)
89 ((E)-7:(Z)-7 ) 55:45)
6 ((E)-7:(Z)-7 ) 58:42)
68 ((E)-10:(Z)-10 ) 53:47)
65 ((E)-10:(Z)-10 ) 57:43)
e
89 ((Z)-2)
23 (82% (Z)-3)
27 (89% (E)-4)
-
f
(
c) Hydrodehalogenation with Me2CHO /AIBN in Refluxing Me2CHOH
(
(
(
E)-2
Z)-2
Z)-2
180
180
180
88 ((E)-2)
85 ((Z)-2)
95 ((Z)-2)
8 ((E)-7:(Z)-7 ) 58:42)
6 ((E)-7:(Z)-7 ) 56:44)
e
(
d) Hydrodehalogenation with LAH in THF at rtg
(E)-2
(Z)-2
(Z)-2
(Z)-2
180
180
180
180
24 ((E)-2)
27 ((Z)-2)
98 ((Z)-2)
37 ((Z)-2)
71 ((E)-7:(Z)-7 ) 54:46)
66 ((E)-7:(Z)-7 ) 55:45)
b
h
52 ((E)-7:(Z)-7 ) 53:47)
a
Typical conditions: substrate, 25 µmol; nucleophile, 80 µmol; solvent, 1.5 mL. b In the presence of 9 µmol of p-dinitrobenzene. Without
c
d
e
f
nucleophile. Typical conditions: substrate, 0.1 mmol; Bu3SnH, 0.1 mmol; AIBN, 10 µmol; solvent, 0.25 mL. Without AIBN. Typical
-
g
conditions: substrate, 0.1 mmol; Me2CHO , 0.2 mmol; AIBN, 10 µmol; solvent, 0.25 mL. Typical conditions: substrate, 18 µmol; LAH,
h
5
5 µmol; solvent, 0.25 mL. In diethyl ether.
Sch em e 2
2 would yield product 6 and the radical anion of 2 that
re-enters the propagation cycle.
The stereoconvergence of the reactions of (E)-2 and
(Z)-2 towards equal E,Z mixtures of 6 and 7 excludes the
possibility that radical 8 has a configurationally stable
bent structure. It is instead either an sp linear or a pair
2
of rapidly interconverting isomeric sp bent radicals: in
both these cases the original configuration of the reagent
would be lost, giving either a static or a dynamically
averaged identical intermediate.5
,15
It is appropriate to
Sch em e 3
compare this situation with the stereochemical outcome
of the reaction of 2 in a vinylic S
N
1 reaction.17 The linear
vinylic carbocation from 2 is captured by 2,2,2-trifluoro-
ethanol giving a 1:1 E:Z mixture of the 2,2,2-trifluoro-
ethyl ethers. The composition of this E:Z mixture is very
similar to those reported in Scheme 2. It is clear that
the ratio of the captured products from a linear inter-
mediate, being either a carbocation or a radical, depends
on the relative steric environments of the two faces of
the vinylic species. Both faces of 8 are sterically almost
the same, and there are only minor electronic differences
of An vs Ph group. This could be the reason for the ca.
Sch em e 4
1
N
:1 product ratios in Scheme 2 as well as in the S 1
1
7
reaction.
The possibility for any bent vinyl radical to give an E,Z
mixture of product(s) is linked to an E,Z equilibration
being faster than the specific reaction channels, e.g., eq
7
a,b in Scheme 4. The reactivity of the latter channels
can be approximately estimated as follows: the rate of
reaction of phenyl radical with a ketone enolate ion is
Hence, it is safe to conclude that the products formed
8
-1 -1
22
according to Scheme 2 are unambiguously produced in a
photostimulated SRN1(V) route (see Scheme 4). The
intermediate R-phenylvinyl radical 8 partitions between
hydrogen atom abstraction (e.g., from the solvent) to give
reckoned to be 3 × 10 M
s
3
in liquid NH (-33 °C),
while rates of hydrogen atom abstraction by phenyl
5
9
-1
-1
radical are in the range of 10 -10
M
s
(at room
7
and combination with the nucleophile to give the
(
22) Amatore, C.; Combellas, C.; Pinson, J .; Oturan, M. A.; Robveille,
•-
radical anion of 6. Exchange of an electron from 6 with
S.; Sav e´ ant, J .-M.; Thi e´ bault, A. J . Am. Chem. Soc. 1985, 107, 4846.

Vinylic SRNV Reaction of Triarylvinyl Halides
J . Org. Chem., Vol. 61, No. 25, 1996 8881
Sch em e 5
Sch em e 6
temperature) depending on the hydrogen donor.23 As-
suming that to a first approximation the reactivity of a
vinyl radical resembles that of an aryl radical,24 we can
estimate a lower limit to the E,Z inversion rate of a bent
9
-1
vinyl radical 8 (i.e., g10 s ) that is consistent with the
observed loss of substrate configuration (Scheme 2). It
may be added that circumstantial evidence for homolytic
decomposition of some vinylic peroxides or peresters is
in favor of the intermediacy of isomeric vinyl radicals that
equilibrate much more quickly than they abstract an
hydrogen atom.5
Sch em e 7
,15
The present results (Scheme 2) are analogous with the
stereochemical outcome of an aliphatic SRN1 substitu-
tion.25 This has been shown to give racemic substitution
products owing to the intermediacy of an alkyl radical,
for which there is a quite general consensus in favor of a
rapidly inverting shallow pyramidal structure.26
Support for the conclusions drawn for the structure of
the reactive intermediate of the SRN1(V) route was
sought. In particular, unambiguous and independent
generation of radical 8 was viewed as helpful for selec-
tively studying its stereochemical behavior, in order to
Vinyl radicals have already been generated by this
method from vinyl halides.5
a,24,30
In all the reported cases
the double bond was substituted by alkyl groups, and the
radicals could be inferred to invert rapidly between E and
Z isomers on the basis of the stereoconvergence ob-
compare it with our observations (Scheme 2). Besides
that, previous investigation4,27 has shown that electron
tained2
4,30,31
(see, e.g., Scheme 6).
31b
transfer to the intermediate vinyl radical (to give a
carbanion) can easily occur in a “reducing environment”
such as that of an SRN1 cycle, where radical anions are
involved. Consequently, it is possible, in principle, that
reduced product 7 arises from two different intermedi-
ates: a configurationally stable vinyl anion and the vinyl
radical. In contrast to what is found in Scheme 2,
however, a larger amount of retention of configuration
This method is exploited here to induce a bona fide
formation of radical 8 from precursor 2: the hydrodeha-
logenated product 7, resulting from H-atom abstraction
from Bu
3
SnH,32 was indeed obtained. In particular,
either (E)-2 or (Z)-2 yielded an identical 55:45 (E)-7:(Z)-7
mixture (Scheme 7). This product distribution is practi-
cally identical with that reported for 7 in Scheme 2. The
identical product distribution in this radical process and
the electron-transfer SRN1(V) process strongly supports
a common intermediate 8 in both reactions as the origin
of the observed stereochemical outcome for the generation
of key product 7.
in product 7 seems likely in this event,5
a,28
if reduction
-
of radical 8 to a configurationally stable carbanion (Vy )
occurs faster than isomerization of 8 (Scheme 5). Inde-
pendent generation of 8 from 2 in the absence of nucleo-
phile 5 would enable an unequivocal study of its stere-
ochemistry in the absence of ET steps associated with
the SRN1(V) process.
A control experiment makes it clear that no thermal
isomerization of the precursors occurs, since (Z)-2 is
recovered configurationally unchanged from refluxing
Ra d ica l Hyd r od eh a logen a tion . Dehalogenation of
alkyl or aryl halides by means of trialkyltin radical
provides an easy access to the corresponding radical
benzene containing Bu
recovery of unreacted (E)-2 after reaction with Bu
3
SnH but no AIBN. Moreover,
SnH
3
species (eq 9).2
4,29
(Scheme 7) reveals no isomerization; this ensures that a
conceivable loss of configuration of the precursor or
•
products due to Bu
nation (eq 10)
3
Sn addition-isomerization-elimi-
AIBN
RX
•
•
Bu SnH
8 Bu Sn
8 Bu SnX + R
(9)
21,29
3
3
3
cannot be the major cause for the
∆
formation of the E,Z-mixtures of 7 in Scheme 7.
(23) (a) Methods in Free Radical Chemistry; Huyser, E. S., Ed.;
Marcel Dekker: New York, 1969-1974; Vols. 1-5. (b) For a more
recent compilation, see: Fossey, J .; Lefort, D.; Sorba, J . Free Radicals
in Organic Chemistry; Masson-Wiley: Paris, 1995.
(
(
(
24) Curran, D. P. Synthesis 1988, 417.
25) Norris, R. K.; Smyth-King, R. J . Tetrahedron 1982, 38, 1051.
26) (a) Lisle, J . B.; Williams, L. F.; Wood, D. E. J . Am. Chem. Soc.
The results of Scheme 7 were confirmed with the two
other stereoindicators, namely, 3 (86% Z) and 4 (91% E).
1
8
976, 98, 227. (b) Bonazzola, L.; Leray, N.; Roncin, J . Ibid. 1977, 99,
348. (c) Paddon-Row, M. N.; Houk, K. N. Ibid. 1981, 103, 5046.
(
27) Gatti, N.; J ugelt, W.; Lund, H. Acta Chem. Scand. 1987, B41,
6
5
46.
(30) Stork, G.; Baine, N. H. J . Am. Chem. Soc. 1982, 104, 2321.
(31) (a) J asperse, C. P.; Curran, D. P.; Ferig, F. L. Chem. Rev. 1991,
91, 1237. (b) Curran, D. P.; J asperse, C. P.; Totleben, M. J . J . Org.
(28) Sargent, G. D.; Browne, M. W. J . Am. Chem. Soc. 1967, 89,
363.
(
29) Giese, B. Radicals in Organic Synthesis: Formation of Carbon-
Chem. 1991, 56, 7169.
(32) Reference 24 quotes k
H-atom abstraction by vinyl radical from Bu SnH.
3
3 × 10 s-1 at 30 °C as the rate of
8
Carbon Bonds; Baldwin, J . E. Ed.; Organic Chemistry Series 5;
Pergamon: Oxford, 1986.
H

8
882 J . Org. Chem., Vol. 61, No. 25, 1996
Galli et al.
Sch em e 8
Sch em e 10
Sch em e 9
As a bona fide counterpart of the ET steps invoked in
Schemes 2 and 9, we add that electrochemical reduction
2
7,37
of vinyl halides has already been investigated.
Re-
These vinylic precursors had been prepared according to
sults consistent with ours are reported, indicating that,
after the uptake of one electron, a vinyl radical is
produced. It can undergo isomerization prior to accepting
1
6
the literature and were available from a previous
investigation.33 Tin radical-induced hydrodehalogena-
tions of mostly (Z)-3 or mostly (E)-4 gave equal E,Z-
mixtures of product 10 (Scheme 8).
a second electron and a proton, ultimately affording a
cis,trans mixture of the alkene product.27,38
This stereoconvergence resulting from the same vinylic
radical generated from two different precursors is again
rationalized either by an sp linear or by a configuration-
It is finally fitting to comment on a subtle source of
complexity in the results of Scheme 2. In fact, another
reactive intermediate of the S
RN1(V) route does exist, in
2
•-
ally unstable sp structure for the radical intermediate
addition to 8, i.e., 2 . The same intermediate is shared
by the 2-propoxide/AIBN route of Scheme 9. In principle,
a vinylic radical anion can be configurationally unstable
because it hosts the extra electron in a π* MO. The
antibonding character of the double bond has been held
at the origin of the cis,trans isomerization observed with
vinylic radical anions lacking suitable leaving groups
9
.
E lect r on -Tr a n sfer -In d u ced H yd r od eh a logen a -
tion . As an additional corroboration of the structural
conclusions derived from the tin-induced radical deha-
logenation, it appeared desirable to study a bona fide
electron-transfer induced hydrodehalogenation of 2 that
would proceed through the intermediacy of radical 8 and
compare its stereochemical outcome with those reported
in Schemes 2 and 7. Inspiration for this experimental
method derives from previous studies of the groups of
Bunnett34 and Sav e´ ant. It is a dehalogenation of the
vinyl halide induced by 2-propoxide ions; radicals from
an initiator (AIBN) remove a hydrogen atom from the
alkoxide ion, transforming it into a powerful electron
donor,36 i.e., acetone radical anion. The radical anion of
the vinyl halide is generated from it by electron transfer
such as the halogens.39
Isomerization of the cis-stilbene
40
radical anion into the trans-radical anion and a few
other examples of isomerizations of vinylic radical anions
41
are known. Consequently, the stereochemical result of
35
our SRN1(V) reaction could be masked by occurrence of a
•-
•-
(E)-2 S (Z)-2 isomerization before that dehalogenation
to form radical 8 has taken place (Scheme 10).
An argument against this route is that the unambigu-
ous generation of 8 by means of tin radical (Scheme 7)
has already delineated the stereochemical behavior of
that particular vinyl radical as a species capable of loss
of memory of the configuration of its vinyl halide precur-
sor(s), as testified by the stereoconvergence obtained in
the formation of key product 7. This has been confirmed
in Scheme 8 for radical 9. Moreover, isomerization of
(eq 11). The subsequent steps are similar to those
•
-
2
could become appreciable only if it is faster than the
described in Scheme 4, with the only exception that
nucleophile 5 is absent and only hydrodehalogenation
may occur (Scheme 9).
rate of C-Br bond cleavage. Typical rates of cleavage of
4
2
7
radical anions of aryl bromides are in the range of 10 -
9
-1
1
0 s . However, for the isomerization of cis-stilbene
When the reaction was conducted with (E)-2 and (Z)-
5
-1
40
radical anion, a rate of 1.4 × 10 s is reported, and
2
7
, hydrodehalogenation took place, giving identical (E)-
:(Z)-7 mixtures either from (E)-2 or (Z)-2. This is again
the isomerization of diethyl maleate f diethyl fumarate
4
1a
radical anions is even slower, the rate constant being
0 s . It seems reasonable to conclude that any (E)-2
S (Z)-2 isomerization will be slower than the following
the same 57:43 (E)-7:(Z)-7 composition reported in
Schemes 2 and 7. A control experiment had shown that
the (Z)-2 precursor was recovered unchanged from reflux
in 2-propoxide/2-propanol solution without AIBN. The
-
1
•-
1
•
-
(37) Encyclopedia of Electrochemistry of the Elements, Org. Sect.;
•
-
generation of 2 by ET step, and the presence of 8 in
the product-determining route of Scheme 9, are thus
warranted.
Bard, A. J ., Lund, H., Eds.; Marcel Dekker: New York, 1980; Vol. 14.
(38) Elving, P. J .; Rosenthal, I.; Hayes, J . R.; Martin, A. J . Anal.
Chem. 1961, 33, 330.
(39) Todres, Z. V. Tetrahedron 1987, 43, 3839; Acta Chem. Scand.
1
990, 44, 535.
(
33) Rappoport, Z.; Apeloig, Y. J . Am Chem. Soc. 1969, 91, 6734;
975, 97, 821, 836.
34) (a) Bunnett, J . F.; Wamser, C. C. J . Am. Chem. Soc. 1967, 89,
712. (b) Bunnett, J . F. Acc. Chem. Res. 1992, 25, 2.
35) Amatore, C.; Badoz-Lambling, J .; Bonnel-Huyghes, C.; Pinson,
J .; Sav e´ ant, J .-M.; Thi e´ bault, A. J . Am. Chem. Soc. 1982, 104, 1979.
36) Wardman, P. J . Phys. Chem. Ref. Data 1989, 18, 1637.
(40) J ensen, B. S.; Lines, R.; Pagsberg, P.; Parker, V. D. Acta Chem.
1
Scand. 1977, B31, 707.
(
(41) (a) Bard, A. J .; Puglisi, V. J .; Kenkel, J . V.; Lomax, A. Faraday
Disc. Chem. Soc. 1973, 56, 353. (b) Yeh, L.-S. R.; Bard, A. J . J .
Electrochem. Soc. 1977, 124, 189.
(42) Andrieux, C. P.; Sav e´ ant, J .-M.; Zann, D. Nouv. J . Chim. 1984,
8, 107.
6
(
(

Vinylic SRNV Reaction of Triarylvinyl Halides
J . Org. Chem., Vol. 61, No. 25, 1996 8883
cleavage of the radical anion, so that the stereoconver-
gence observed in the ET pathways of Schemes 2 and 9
is due only to the intermediacy of vinyl radical 8. Our
own experience with radical anions of vinyl halides
generated by cyclic voltammetry confirms fast cleavage
rates of the C-halogen bond.4 In addition, no isomeriza-
tion of the recovered precursor is detected from the ET-
induced experiments (Schemes 2 and 9). This is consis-
tion, in which the predicted stereochemical outcome is
retention of configuration.3
Reaction in the presence of the electron scavenger
p-dinitrobenzene gave no conversion to 7 within the same
time span. From these facts, the intermediacy of 8 and
the relevance of ET steps in this reaction, as delineated
in Scheme 11, seem likely.
Con clu sion s. Our investigation excludes the possibil-
ity of a bridged or a bent and configurationally stable
structure for radical 8. It cannot distinguish between
an sp linear structure or a pair of rapidly interconverting
•
-
•-
tent with the fact that the (E)-2 or (Z)-2 generated
by ET steps are lost by a consecutive and very fast
•
-
cleavage step. In conclusion, E,Z isomerization of 2 ,
followed by return to the isomeric vinylic halides, does
not appear to appreciably interfere with the stereochem-
ical fate of intermediate 8. The possibility to study the
isomerization of the radical anion of a vinyl halide, in
competition with its cleavage, represents per se an
interesting experimental challenge, which could be ad-
dressed in the future on proper precursors.4
2
46
isomeric sp bent radicals. Ongoing calculations, how-
ever, preliminarly show that a conjugated R-vinylvinyl
radical is linear. If the latter is taken as a model for the
R-phenylvinyl radical in solution, it seems reasonable
that the stereochemistry described in this paper can be
ascribed to the intermediacy of linear 8. The very
presence of this vinylic radical in the SRN1(V) propagation
cycle has been confirmed by comparison of the stereo-
chemical outcome of this reaction with that of different
reactions that unambiguously give rise to 8 through the
agency of alternative mechanisms. Evidence for an ET
step of hydrodehalogenation of vinyl halide 2 by LAH is
also provided.
3,44
Hyd r od eh a logen a tion w ith LAH. Hydrodehaloge-
nation of alkyl and aryl halides by lithium aluminum
hydride (LAH) takes place easily, but its mechanism has
been strongly debated, as summarized in a recent paper.3
One possibility is a radical-chain mechanism with a
4b
4
5
propagating cycle similar to that of Scheme 4, even
though its initiation step is uncertain (see Scheme 11,
where substrate 2 is used for demonstration).
Exp er im en ta l Section
The instrumentation has already been described.2,4 Deter-
Sch em e 11
mination of the reduction potential of compounds 2-4 by cyclic
-
1
voltammetry was conducted in THF (at a 500 mV s sweep
2
w 8 (initiation)
rate) as reported in a previous paper.4 Precursors 2-4 and
products (E)-10:(Z)-10 (72:28) were prepared as previously
+ AlH4- f 7 + AlH3•-
8
described.
17,33
Products (E)-7 (mp 58-59 °C) and (Z)-7 (mp
16
9
0-91 °C) were prepared according to Curtin et al. Pina-
colone was distilled from anhydrous K CO ; freshly sublimed
t-BuOK was used to generate the enolate ion from pinacolone.
Commercial Me SO (C. Erba RPE, 99.5%) was dried on
AlH3•- + 2 f AlH + 2
•-
2
3
3
2
2•-
-
activated molecular sieves and thoroughly purged with argon
for 30 min prior to use in order to remove volatile acidic
impurities.4 Benzene was dried over sodium, and THF was
distilled from benzophenone radical anion. Commercial Li-
f 8 + Br
Without generalization to other kinds of substrates, we
report our results with (E)-2 and (Z)-2, which were
exploited as stereoindicators of the hydrodehalogenation
reaction with LAH in THF at room temperature. An (E)-
/(Z)-7 mixture was again obtained from the two isomeric
precursors (Scheme 12), with the “usual” composition of
AlH
4
, Me
2 3
CHOH, AIBN, and Bu SnH were used.
6
-p-An isyl-2,2-d im eth yl-5,6-d ip h en yl-5-h exen -3-on e (6).
Reaction of 0.9 g of pinacolone (9 mmol), 1.0 g of sublimed
t-BuOK (9 mmol), and 1.1 g of (Z)-2 (3 mmol) in 25 mL of Me
7
2
-
SO was conducted in a Rayonet photochemical reactor (16 “350
nm” lamps) for 90 min.2 After usual workup,2 the crude
mixture (1.5 g) was chromatographed on silica gel with 5:1
petroleum ether (40-70 °C)/diethyl ether and then with 2:1
Sch em e 12
petroleum ether (40-70 °C)/benzene eluents to yield 400 mg
1
(
(
0
(
35%) of 6, mp 75-80 °C, as an E:Z mixture: H NMR δ
CDCl
.92 (s, 9H, E,Z CMe
E,Z C)O), 158.6, 143.3, 142,2, 135-125, 113, 55.1, 44.7, 44.2,
6.3; HRMS 384.2084, C27 requires 384.2082.
P r oced u r es. Details on SRN1 experiments under photo-
stimulation and on the radical dehalogenation experiments by
3
) 7.3-6.3 (m,14H), 3.75 (s, 2H), 3.6 (s, 3H), 0.96 and
13
3
3
); C NMR δ (CDCl ) 213.6 and 213.5
5
4:46 (E)-7:(Z)-7 identical with that previously reported
2
28 2
H O
in Schemes 2, 7, and 9. The unreacted (Z)-2 was
recovered configurationally unchanged. This reduction
reaction cannot be an ionic bimolecular vinylic substitu-
2
,4
AIBN/Bu
3
SnH have been given described previously.
De-
-
scription of a typical i-PrO /AIBN procedure of hydrodehalo-
genation follows. One mL of a freshly prepared 0.4 M i-PrONa/
i-PrOH solution was added to a 2 mL i-PrOH solution of 44
mg of (Z)-2 (0.12 mmol), 6 mg AIBN (0.04 mmol), and 10 mg
of biphenyl (internal standard; 0.065 mmol). The solution was
refluxed for 5 h and directly analyzed (GC and GC-MS; no
workup). Similarly, a LAH-induced dehalogenation was con-
ducted in 2 mL of anhydrous THF with 22 mg of (E)-2 (0.06
(
43) A reviewer had pointed out that the radical anion of the
•
-
substitution product (6 ), having no leaving group, could live long
enough to isomerize. This cannot be excluded. However, if the vinyl
radical 8 is already linear or behaves like it (i.e., a rapidly intercon-
verting mixture), then whatever its successor species 6 is doing it is
irrelevant to the stereochemical outcome. At any rate, our stereochem-
ical conclusions are drawn on the loss of the original stereochemistry
that is verified in the formation of hydrodehalogenation product 7,
whose generation (in Schemes 2, 7, and 9) directly stems from radical
•
-
4
mmol) and 2 mg of LiAlH (0.053 mmol); after being stirred
at room temperature for 4 h, the internal standard was added
and the solution analyzed by GC and GC-MS. In cases where
8
. However, we do plan to investigate the rate of isomerization of
radical anions from 6, or similar compounds, by means of cyclic
voltammetry.44
(
44) Work in progress, in collaboration with the group of Prof. H.
Lund, Århus University, Denmark.
45) Ashby, E. C. Acc. Chem. Res. 1988, 21, 414. Ashby, E. C.;
Deshpande, A. K.; Patil, G. S. J . Org. Chem. 1995, 60, 663.
(46) Galli, C.; Mencarelli, P.; Rappoport, Z. Work in progress. The
calculations are carried out by an ab initio DFT (BLYP/6-31G**)
method.
(

8
884 J . Org. Chem., Vol. 61, No. 25, 1996
Galli et al.
p-dinitrobenzene was added as an inhibitor, it was employed
in a 20-40% molar amount with respect to the substrate.
An a lysis of Dia ster eoisom er ic Com p osition of Re-
a gen ts a n d P r od u cts. Quantitative GC analyses of the
reaction mixtures were performed by the internal standard
method, suitable response factors being determined on pure
samples of compounds 6 and 7. The peaks of (E)-6 and (Z)-6,
as well as those of (E)-7 and (Z)-7, were sufficiently well
separated by the capillary columns employed in GC and GC-
MS analyses (30 m × 0.25 mm SE-54 and 25 m × 0.20 mm
methyl silicone gum, respectively) in order for reliable integra-
tion of the corresponding areas to be performed. Products 10
were less efficiently separated to the E and Z isomers by gas
Photostimulated reactions of mostly (Z)-3, as also of mostly
(E)-4, with the enolate ion of pinacolone did not produce the
expected substitution product or the hydrodehalogenated
product, while consumption of the starting reagents was
indeed verified. Only p-methoxybenzophenone (ca. 30-40%)
was detected as a product after 20 min reaction. Formation
33,47
of this product is in agreement
with the intermediacy of a
vinylic carbocation.1
8,20
Ackn owledgm en t. Support from the Italian MURST
and from the U.S.-Israel Binational Science Foundation
(BSF), J erusalem, Israel (to Z.R.), are gratefully
acknowledged.
1
chromatographic analysis. However, H NMR analysis was a
suitable analytical tool in this case. The signals of the MeO
3
3
groups, at δ 3.84 and 3.74 for (Z)-10 and δ 3.80 and 3.73 for
J O961007V
(E)-10 could be followed and integrated. The diastereoisomeric
composition of recovered 2 was checked by GC and GC-MS,
1
while H NMR analysis was again employed in the case of 3
3
3
and 4.
(47) Ruberu, S. R.; Fox, M. A. J . Am. Chem. Soc. 1992, 114, 6310.