Remote asymmetric induction in Michael additions of allylic sulfones

Full text of DOI:10.1021/jo982004g

8
J . Org. Chem. 1999, 64, 8-9
Sch em e 1
Rem ote Asym m etr ic In d u ction in Mich a el
Ad d ition s of Allylic Su lfon es
Eugene Ghera,* Victoria Kleiman, and Alfred Hassner*,1
Department of Chemistry, Bar-Ilan University,
Ramat-Gan 52900, Israel
Received October 5, 1998
Chiral auxiliary-controlled asymmetric Michael reactions
are a topic of current interest in asymmetric synthesis.2 In
this context, Michael additions of allylic-type anions, part
of chiral donor moieties, were mostly related to organophos-
phorus3 and R-sulfinyl4 anions. The reported conjugate
additions were γ-regioselective, and the achievement of
diastereofacial selectivity was assisted by cyclic platforms
on the anionic substrate or by cyclic Michael acceptors, to
reduce the conformational flexibility of the chelated inter-
mediates. Extension of this methodology to acyclic substrates
is more challenging. We report herein on the possibility to
convey remote asymmetric information in conjugate addi-
tions involving acyclic substrates, with allylic R-sulfonyl
anions as part of the transferred chiral moiety.
Sch em e 2
Taking advantage of our5 and Najera’s group’s6 findings
concerning the high anti diastereoselectivity7 and R-regio-
selectivity obtained in Michael reactions of allylic R-sulfonyl
carbanions with open-chain R,â-unsaturated esters, we
envisaged the possibility of transmitting asymmetry in these
reactions by placing a remote chiral auxiliary in the allylic
sulfone donor. The aminated sulfone 26 was chosen as the
model compound because intramolecular Li bridging in the
lithiated intermediate8 was assumed to enhance a facially
selective approach: we indeed found that the high anti
diastereoselectivity (>97%) obtained in the conjugate addi-
tion of 2 with ethyl crotonate (LDA, THF) was less affected
by adding to the reaction mixture chelation-disrupting
cosolvents9 than in identical reactions of 1. Moreover, the
reaction of 2 with the epoxy ester 4 afforded a major
stereomer 5 (>72% yield) with four contiguous stereocenters,
which was further cyclized under basic conditions to the
Ta ble 1. Dia ster eom er ic Ra tio (d r ) of Ad d u cts Sh ow n in
Sch em e 2
yield
entry
R
R′
reaction conditions
(%)
dr a :b
1
2
3
4
5
6
Me
Me
Me
Ph
Et LDA, -78 °C, 1 h
72
89
77
80
8, 82:18
8, 87:13
8, 89:11
9, 89:11
Et LHMDS, -95 °C, 1.5 h
Et LHMDS, -108 °C, 2 h
Et LHMDS, -108 °C, 3.5 h
n-propyl Me LHMDS, -108 °C, 3 h
Me
75 10, 90:10
57 11, 62:38
tBu LDA, -60 °C, 5 ha
a
No reaction at lower temperature.
lactone-fused hexahydroazepine 610 (21%, Scheme 1). Hence,
the (S)-N-(1′-phenylethyl) aminated sulfone 7 was prepared
and treated with LDA (1.2 equiv) in THF at -78 °C, followed
by an unsaturated ester (1.4 equiv). As determined by 1H
NMR analysis of the crude product mixture and subsequent
chromatographic purification, only two out of four possible
diastereomers were formed, both with an anti arrangement
at the newly formed stereogenic centers (8-11a ,b, Scheme
2 and Table 1).10 The diastereomeric ratio (dr) (82:18) was
further improved to a remarkable remote asymmetric induc-
tion of ∼9:1 (entries 3-5) by changing the Li base and
lowering the temperature, under otherwise similar condi-
tions. The introduction of a bulky tert-butyl ester group
resulted in a less selective diastereomeric ratio (entry 6).
Conjugate addition of 7 to 4-bromocrotonate and tandem
ring closure (eq 1)11 gave the cyclopropane carboxylate 12a ,b
(9:1 dr). Separation of the major diastereomer of 12 (mp
114-115 °C, 60%, [R]D ) -133°) enabled the determination
of its absolute configuration by X-ray crystallography as the
(3S,1′S) amine derivative; by analogy, the same absolute
configuration can be assigned for all major diastereomers
designated as a in Table 1.
(1) Stereochemistry. 90. Part 89: Namboothiri, I. N. N.; Hassner, A. J .
Org. Chem. 1997, 62, 485.
(2) For reviews, see: Schmaltz, H. G. In Comprehensive Organic Chem-
istry, Trost, B. H., Ed.; Pergamon Press: Oxford, 1991; Vol. 4, pp 199-237.
Perlmutter, P. In Advanced Asymmetric Synthesis; Stephenson, G. R., Ed.;
Chapman & Hall: London, 1996, pp 222-229. Walker, A. J . Tetrahedron:
Asymmetry 1992, 3, 961-998.
(3) Hua, D. H.; Chan-Yu-King, R.; McKie, J . A.; Myer, L. J . Am. Chem.
Soc. 1987, 109, 5026-5029. Haynes, R. K.; Stokes, J . P. Hambley, T. W.
Chem. Commun. 1991, 58-60. Hanessian, S.; Gomtsyan, A.; Payne, A.;
Herve´, Y.; Beaudoin, S. J . Org. Chem. 1993, 58, 5032-5034. Hanessian,
S.; Gomtsyan, A. Tetrahedron Lett. 1994, 35, 7509-7512. Tanaka, K.; Ohta,
Y.; Fuji, K. J . Org. Chem. 1995, 60, 8036-8043. Denmark, S. E.; Kim, J .-
H. J . Org. Chem. 1995, 60, 7535-7547.
(4) Hua, D. H.; Venkataraman, S.; Coulter, M. J .; Sinai-Zingde, G. J .
Org. Chem. 1987, 52, 719-728. Hua, D. H.; Bharathi, S. N.; Panangadan,
J . A. K.; Taujimoto, A. J . Org. Chem. 1991, 56, 6998-7007. Hua, D. H.;
Park, J .-G.; Katsuhira, T.; Bharati, S. N. J . Org. Chem. 1993, 58, 2144-
2150.
(5) Ghera, E.; Yechezkel, T.; Hassner, A. J . Org. Chem. 1996, 61, 4959-
4966. Ghera, E.; Yechezkel, T.; Hassner, A. Tetrahedron Lett. 1990, 31, 3653.
(6) Alonso, D. A.; Falvello, L. R.; Mancheno, B.; Najera, C.; Tomas, M.
J . Org. Chem. 1996, 61, 5004-5012.
(7) Syn and anti designations are based on the extended form including
both anion stabilizing groups; see: Oare, R. A.; Heathcock, C. H. In Topics
in Stereochemistry; Eliel, E. L., Wilen, S. H., Eds.; Wiley: New York, 1989;
Vol. 19, pp 227-407.
(8) See, e.g.: Eisch, J . J .; Galle, J . E. J . Org. Chem. 1980, 45, 4534-
4536.
(9) For 1, addition of 10% DMPU resulted in a change of the anti/syn
ratio of adducts from 88:12 (84%) to 67:33 (83%); with 10% HPMA the ratio
was 40:60. For the donor 2, the anti/syn ratio changed from >97% anti to
89:11 (with 10% DMPU, 92%) and to 60:40 (with 10% HMPA, 76%).
(10) The stereochemistry was established by 1H and 13C NMR analysis
and NOESY data.
(11) Ghera, E.; Ben David, Y. Tetrahedron Lett. 1979, 4603-4606.
10.1021/jo982004g CCC: $18.00 © 1999 American Chemical Society
Published on Web 12/19/1998

Communications
J . Org. Chem., Vol. 64, No. 1, 1999
9
Ta ble 2. In flu en ce of th e Ch ir a l Au xilia r y on d r (Eq 3)
ester
reaction
time (h)
yield
(%)
entry donor
R′
R′′
dr a :b
1
2
3
4
5
6
7
8
17
18
19
19
20
20
20
20
Me
Me
Me
Ph
Me
Ph
Et
Et
Et
Et
Et
Et
2
1
1.5
3
1
5.5
4
4
83
84
73
76
94
95
89
73
21, 74:26
22, 73:27
23, 1:1
Donors with additionally substituted amines (13 and 14)
gave diastereomeric pairs (15, 16, eq 2) with lower diaste-
reoselectivity; hence, hindering groups obstruct the trans-
mission of asymmetry, as found above also for tert-butyl
esters.
24, 1:1
25, 93:7
26, 94:6
27, 93:7
28,a 93:7
n-propyl Me
CH2Br Et
a
Cyclopropanecarboxylate, analogue of 12 was obtained.
F igu r e 1. Preferential transitional structure for Michael addition.
ring bound to the chiral center.13 Starting from this premise,
we performed conjugate additions with donors bearing a
naphthyl instead of a phenyl group at the chiral center with
the hope that the bulkier aromatic group would improve the
proximity effect. Indeed, enhancement of dr (93:7) was
determined in the obtained high-yield products (entries
5-7).
The diastereofacial approach of the carbanion can be
rationalized by an examination of transition structures: an
enhanced interaction of Li with the phenyl group at the
chiral center enabling intramolecular Li bridging in the
donor, and intermolecular Li chelation with the ester car-
bonyl leads to the 3S adduct (Figure 1).
Variation of the chiral auxiliary can influence asymmetric
induction.12 In an effort to rationalize the remote transmis-
sion of asymmetry, several allylic sulfones with different
amine-bound chiral substituents were reacted with unsatur-
ated esters under identical reaction conditions (eq 3 and
Table 2). The most striking effect was observed by changing
Complex-induced proximity effects have been shown to
control the course of some chemical reactions.14 Recently,
dilithiated enolates of amide-bound chiral auxiliaries have
been found to lead to diastereoselective substitutions15 and
to exert long-distance diastereocontrol over substitutions at
sulfone-activated carbanions.16
In summary, a new pathway of remote asymmetric
induction in Michael reactions involving allylic R-phenyl-
sulfonyl carbanions in chiral donors has been disclosed. The
transmission of asymmetry was found to depend on the
presence of an aromatic nucleus bound to the chiral center.
the phenyl group at the chiral center to a cyclohexyl: the
asymmetric induction was reduced to nil, an equal amount
of diastereomers being formed (entries 3 and 4). Hence, the
intramolecular Li bridging in the transition state and
stereofacial approach is not sufficient for conveying asym-
metry in the product unless there is an additional interac-
tion, presumably of Li with the π electrons of an aromatic
Ack n ow led gm en t. Support of this research by a grant
from the US-Israel Binational Science Foundation is
gratefully acknowledged. The authors wish to thank Dr.
H. E. Gottlieb for help with the NMR analysis and Dr. S.
Cohen, Hebrew University, J erusalem, for the X-ray crystal
structure determination of 12.
(12) Burgess, L. E.; Meyers, A. I. J . Am. Chem. Soc. 1991, 113, 9858-
9859.
(13) Posner, G. H.; Lentz, C. M. J . Am. Chem. Soc. 1979, 101, 934-946.
(14) Beak, P.; Meyers, A. I. Acc. Chem. Res. 1986, 19, 356-363. Beak,
P.; Basu, A.; Gallagher, D.; Park, Y. S.; Thayumanavan, S. Acc. Chem. Res.
1996, 29, 552-560.
(15) Pippel, D. J .; Curtis, M. D.; Du, H.; Beak, P. J . Org. Chem. 1998,
63, 2-3.
(16) Linnane, P.; Magnus, N., Magnus, P. Nature 1997, 387, 799-801.
Magnus, N.; Magnus, P. Tetrahedron Lett. 1997, 38, 3491-3494.
Su p p or tin g In for m a tion Ava ila ble: Experimental proce-
dures, NMR spectral data for new compounds, and X-ray data for
compound 12 (79 pages).
J O982004G