Double-stereodifferentiating crotylation reactions with chiral (E)-crotylsilanes. Evaluation of a new approach for the synthesis of polypropionate-derived natural products

Full text of DOI:10.1021/ja962877x

J. Am. Chem. Soc. 1996, 118, 12475-12476
Double-Stereodifferentiating Crotylation Reactions
12475
with Chiral (E)-Crotylsilanes. Evaluation of a New
Approach for the Synthesis of
Polypropionate-Derived Natural Products
Nareshkumar F. Jain, Norito Takenaka, and James S. Panek*
Department of Chemistry, Metcalf Center
for Science and Engineering
5
90 Commonwealth AVenue, Boston UniVersity
Boston, Massachusetts 02215
ReceiVed August 16, 1996
Lewis acid-promoted allylation and crotylation reactions of
chiral R-substituted aldehydes have been extensively studied
1
and continue to be an active area of research. By way of
analogy, chiral allyl metal reagents may be thought of as
propionate- and acetate-enolate equivalents for diastereo- and
enantioselective construction of stereochemically well-defined
homoallylic alcohols. Because these reactions complement the
aldol reactions, they are among the most important groups of
organometallic reagents available for the control of acyclic
stereochemistry. It is perhaps interesting to note that, in contrast
to the aldol reaction, there is no known biological model for
crotylation.2 During the stereochemical course of this reaction
Figure 1.
Table 1. Lewis Acid-Promoted Additions of Chiral
(E)-Crotylsilanes to Chiral â-Alkoxy Aldehydes
3
type, as well as the Mukaiyama aldol reaction the emerging
hydroxyl-bearing stereocenter is generally controlled by the
inherent diastereofacial bias of the aldehyde.4 In this paper,
we report that the stereochemical course of these double-
stereodifferentiating reactions is determined by the local chirality
of the individual reaction partners. We have demonstrated that
under nonchelation-controlled reaction conditions the diaster-
eomeric relationships between R-methyl and â-alkoxy group
of the chiral aldehydes does not reinforce carbonyl π-facial
selectivity.5 We have previously demonstrated that diastereoface
selectivity can be turned over with chiral silane reagents in the
presence of TiCl4 and chiral R-alkoxy aldehydes. Those
experiments have shown that this common organizational feature
of a bidentate Lewis acid can be reinforced or prevented by
choice of protecting group on the aldehyde. Specifically, with
6
a
â-alkyl-substituted silane reagents, the configuration of the
Refers to the stereochemical relationship of the newly formed C
Cl at -78 °C with
(1.1 equiv). Ratios of diastereomers (5,6-syn:5,6-anti) were
5
-
C
6
bond. b All reactions were carried out in CH
TiCl
determined by H NMR analysis on the crude reaction mixtures. Yields
are reported for pure diastereomers after purification by chromatogra-
phy.
2
2
C-SiR3 center determines the absolute stereochemistry of the
center bearing the methyl group, while the chirality of the
aldehyde controls the absolute stereochemistry of the oxygen
bearing stereocenter. The unique features of these reagents are
illustrated using the stereochemical models in Figure 1, where
open TS models are depicted for the enantiomeric silanes and
4
1
of diastereoselectivity (Table 1). However, the TiCl4-promoted
reactions of 2a with (R)-silane produced the 5,6-anti-6,7-anti
homoallylic alcohol 4 with an excellent level of diastereose-
lectivity. Presumably, these reactions proceed through a Cram
chelate transition state model.
aldehyde 2b. For example, the reaction of (S)-3-(benzyloxy)-
7
2
-methylpropanal (2a) with â-alkylsilane reagent (S)-1 and
TiCl4, a bidentate Lewis acid-promoting chelation, produced
the 5,6-syn-6,7-anti homoallylic alcohol 3 with a good level
9
8
10,11
It is observed that 6,7-anti
(
1) For recent reviews, see: (a) Yamamoto, Y.; Asao, N. Chem. ReV.
(
8) The relative and absolute stereochemistry of all crotylation products
1
993, 93, 2207-2293. (b) Roush, W. R. In ComprehensiVe Organic
was assigned through the measurement of a three-bond coupling constant
of corresponding six-member acetonide (see Supporting Information for
details). For example, see: Masse, C. E.; Panek, J. S. Chem. ReV. 1995,
Synthesis; Heathcock, C. H., Ed.; Pergamon Press: Oxford, 1991; Vol. 2,
pp 1-53. (c) Fleming, I. Chem. Soc. ReV. 1981, 10, 83-99.
(
2) Staunton, J. Angew. Chem., Int. Ed. Engl. 1991, 30, 1302-1306
9
5, 1293-1316 and references therein.
(
(
3) (a) Mukaiyama, T.; Banno, K.; Narasaka, K. J. Am. Chem. Soc. 1974,
9) In a related unpublished example (eq 1) that bears relevance to
9
6, 7503-7509. (b) Gennari, C. In ComprehensiVe Organic Synthesis:
homoallylic alcohol 4, we have documented that the reaction of aldehyde
Additions to C-X π-Bonds Part 2; Trost, B. M., Fleming, I., Heathcock, C.
7
e with (S)-1 produces 5,6-anti-6,7-anti homoallylic alcohol 25.
H., Eds.; Pergamon Press: New York, 1991; Chapter 2.4.
(
4) (a) Panek, J. S.; Beresis, R. T. J. Org. Chem. 1993, 58, 809-811.
(
1
b) Jain, N. F.; Cirillo, P. F.; Pelletier, R.; Panek, J. S. Tetrahedron Lett.
995, 36, 8727-8730.
5) (a) Evans, D. A.; Dart, M. J.; Duffy, J. L.; Yang, M. G. J. Am. Chem.
Soc. 1996, 118, 4322-4343.
6) For the preparation of (R)- and (S)-silane reagents, see: (a) Jain, N.
(
(
F.; Cirillo, P. F.; Schaus, J. V.; Panek, J. S. Tetrahedron Lett. 1995, 36,
(10) (a) Cram, D. J.; Kopecky, K. R. J. Am. Chem. Soc. 1959, 81, 2748-
8
1
723-8726. (b) Panek, J. S.; Yang, M. G.; Solomon, J. J. Org. Chem.
2755. (b) Reetz, M. T. Acc. Chem. Res. 1993, 26, 462-468.
993, 58, 1003-1010.
(11) (a) Panek, J. S.; Cirillo, P. F. J. Org. Chem. 1993, 58, 294-296.
(b) Mikami, K.; Kawamoto, K.; Loh, T.-P.; Nakai, T. J. Chem. Soc., Chem.
Commun. 1990, 1161-1163. (c) Fleming, I. Chemtracts 1991, 4, 21. Also
see ref 4b for chelation-controlled open transition structure.
(
7) (a) Ireland, R. E.; Thaisrivongs, S.; Dussault, P. H. J. Am. Chem.
Soc. 1988, 110, 5768-5779. (b) Massad, S. K.; Hawkins, L. D.; Baker, D.
C. J. Org. Chem. 1988, 48, 5180-5184.
S0002-7863(96)02877-6 CCC: $12.00 © 1996 American Chemical Society

12476 J. Am. Chem. Soc., Vol. 118, No. 49, 1996
Communications to the Editor
Table 2. Lewis Acid-Promoted Reactions of Chiral Aldehydes
Figure 2.
product is preferred under chelation-controlled conditions, while
the absolute stereochemical relation of the methyl bearing
stereogenic center at C5 is dictated by the absolute configuration
of the C-SiR3 bond. In contrast to the (benzyloxy)-substituted
case, the reaction of (S)-3-((tert-butyldiphenylsilyl)oxy)-2-
methylpropanal (2b) and the silane reagent (R)-1 with TiCl4
produced the 5,6-syn-6,7-syn homoallylic alcohol 5 with a high
level of Felkin induction.12 In this example, chelation is
1
3
prevented by the use of the bulky silyl protecting group.
However, reaction of 2b with (S)-1 silane and TiCl4 provided
the complementary 5,6-anti-6,7-syn homoallylic alcohol 6 with
Felkin induction. These results suggest that Felkin induction
controls the stereochemistry of emerging C6 hydroxy group
while stereochemistry of the methyl bearing stereogenic center
at C5 is independently controlled by the absolute configuration
of the C-SiR3 bond.
Aldehydes 7 (Figure 2) bearing stereogenic centers at the R-,
â-, and γ -positions were designed to provide a closer analogy
to bond constructions and synthons that are likely to be
encountered in the synthesis of polypropionate-derived antibiot-
ics. Reactions of silane reagents (S)-1 and (R)-1 with the
silyloxy aldehydes 7a-d, were used to probe the diastereose-
lectivity of double-stereodifferentiating crotylation methodol-
1
4
ogy. The results of those experiments are summarized in
Table 2. We have examined the reactions of the illustrated
silane reagents with highly oxygenated aldehydes bearing silicon
protecting groups to prevent chelation with TiCl4.15 Aldehydes
7
a and 7c are chosen for our discussion to determine the
influence on diastereoselection in the presence of R-, â-, and
γ-stereocenters bearing opposite relative stereochemical rela-
tionships, where we have shown that the absolute configuration
of the newly formed hydroxyl stereocenter is determined by
the diastereofacial bias of the chiral aldehyde and that the
absolute stereochemistry of the emerging methyl group is
determined by chirality of the silane reagent.
For example, the reactions of aldehyde 7a with the silane
reagent (R)-1, aldehyde 7c with (S)-1, and 7d with (R)-1
produced 5,6-syn-6,7-syn homoallylic alcohols 8, 9, and 10 with
nearly complete stereocontrol for Felkin induction. The comple-
mentary 5,6-anti-6,7-syn homoallylic products 11, 12, and 14
are formed, respectively, in the reactions of aldehydes 7a, 7b,
and 7d with the silane reagent (S)-1 and 13 is formed from 7c
with (R)-1, with high levels of Felkin induction. Importantly,
these complex aldehydes exhibit excellent levels of Felkin
induction with the stereochemistry of the emerging methyl group
at C5 being determined by the absolute chirality of the silane
reagent. An important trend associated with this set of experi-
ments is that silane reagents (R)-1 and (S)-1 override the 1,3-
a
Refers to the stereochemical relationship of the newly formed C
5
-
C
6
bond. b All reactions were carried out with 1.1 equiv of TiCl
CH Cl
4
in
2
2
at -78 °C. Ratios of diastereomers (5,6-syn:5,6-anti) were
1
determined by H NMR analysis on the crude reaction mixtures. Yields
are reported for pure diastereomers after purification by chromatogra-
phy.
5
induction associated with chiral aldehydes and are consistently
predisposed to Felkin induction as long as the aldehydes contain
oxygen protecting groups that prevent chelation (i.e., silicon-
9
based protecting groups).
In summary, we have documented that in double-stereodif-
ferentiating crotylation reactions, the diastereoselection and the
absolute stereochemistry are determined by the local chiralities
of the aldehyde and the silane reagent. The chemistry should
be useful in the synthesis of complex organic molecules and
polypropionate-derived natural products.
Acknowledgment. We are grateful to Ms. Annette S. Kim and Dr.
Joseph L. Duffy (Harvard University) for helpful discussions. Financial
support was obtained from the NIH (RO1 CA56304).
(
12) Cherest, M.; Felkin, H.; Prudent, N. Tetrahedron Lett. 1968, 2199-
204. (b) Anh, N. T.; Eisenstein, O. NouV. J. Chim. 1977, 1, 61-70.
13) (a) Roush, W. R.; VanNieuwenhze, M. S. J. Am. Chem. Soc. 1994,
2
(
1
2
16, 8536-8543. (b) Keck, G. E.; Abbott, D. E. Tetrahedron Lett. 1984,
Supporting Information Available: General experimental proce-
dures and spectral data for all intermediates and final products (20
pages). See any current masthead page for ordering and Internet access
instructions.
5, 1883-1887. (c) Keck, G. E.; Savin, K. A.; Cressman, N. E. K.; Abbott,
D. E. J. Org. Chem. 1994, 59, 7889-7896. (d) Marshall, J. A.; Wang X.-j.
J. Org. Chem. 1991, 56, 3211-3213.
(
14) For the preparation of aldehydes 7a-d, see Supporting Information.
15) BF3‚OEt2 and SnCl4 proved to be less effective in these crotylation
(
reactions.
JA962877X