C O M M U N I C A T I O N S
Scheme 2. Transformations of Vinyl Epoxide 10a
Table 2. Substrate Scope of Propargylsilane Additions
ï
a Reagents and conditions: (a) NaN3, DMF, 70 C; TBAF, THF, room
temp; (b) I2, CH2Cl2, room temp.
(eq 6).15 Intermediate O-silylated allenic alcohol was observed in
>98:2 dr, and 12 was subsequently isolated after silyl deprotec-
tion.16 By means of a corollary, the reaction of NaSCN with 10
afforded the identical product 12, albeit in lower yield associated
with incomplete conversion and a lower diastereoselectivity (93:7
dr). Treatment of 10 with I2 also transpired to be an effective
strategy to furnish dihydrofuran 13 as a single diastereomer (eq
7).17
In conclusion, we have developed the first enantioselective
carbonyl addition of propargylsilanes. This reaction proceeds with
high enantioselectivity and excellent diastereoselectivity, to give
vinyl epoxides representing a new paradigm in propargylsilane-
carbonyl additions. All products (except silylether 11) are highly
crystalline solids and may be converted to the corresponding allenic
alcohols and dihydrofuran derivatives.
Acknowledgment. Support has provided by the NSF (Grant
CHE-9907094). Y.A. gratefully acknowledges an AAUW Interna-
tional Predoctoral Fellowship. Marcus J. C. Long and Vijay
Gananaseideken are acknowledged for intellectual discussions.
a Reactions were carried out with 1.5 equiv of propargylsilanes in 0.2
M toluene (from 0.1 tï 2.0 mmol scales of 2). b Enantiomeric excesses were
determined by HPLC using Chiracel AD-H column. The data represent the
ee’s of unpurified products prior to recrystallization. c Results with catalyst
1b. d Absolute stereochemistry determined by Mosher’s ester analysis of
the derivatized product 12 and the rest assigned by analogy.
Supporting Information Available: Experimental details, char-
1
acterization data, HPLC enantiomer analysis, and H and 13C NMR
spectra for all new compounds. This material is available free of charge
Al(III)-pybox complexes afforded any reactivity.11 However, Sc-
(III) was superior both in terms of reaction selectivity and yield. A
solvent survey using catalyst 9e indicated that the product ee and
the reaction conversion showed opposite dependences on solvent
polarity (entries 5-7). Further screening of other reaction param-
eters and additives did not lead to an acceptable level of enantio-
selection. Accordingly, we examined the potential of an alternative
ligand scaffold. We chose the chiral Al(III)-sal-BINAM catalysts
1a-c that we have characterized crystallographically.1 Initial results
were encouraging (entries 8-10), and a general system was
discovered which afforded high yields and enantioselectivities using
catalyst 1c (Table 2, eq 5). Two points are noteworthy: (i) 1a was
inactive; however, catalysts 1b and 1c both displayed similar
enantioselectivity, but the former diminished reaction conversion
by 3-fold across a range of substrates.12 (ii) Catalyst 1c specifically
needed in-situ preparation from 1a with AgOTf.13 Importantly, the
new reaction was shown to be applicable to propargylsilanes bearing
both saturated and unsaturated functions (Table 2, entries 1-7).
As this methodology is a non-oxidative process, the epoxide
function was established with complete regioselectivity, even in
oxirane products formally derived from triolefinic substrates (entries
6 and 7). In addition, the presence of remote polar substituents was
also tolerated (entry 8).
References
(1) Evans, D. A.; Janey, J. M.; Magomedov, N.; Tedrow, J. S. Angew. Chem.,
Int. Ed. 2001, 40, 1884.
(2) Brook, M. A. In Silicon in Organic, Organometallic, and Polymer
Chemistry; Wiley: New York, 2000.
(3) (a) Fleming, I. In ComprehensiVe Organic Synthesis; Heathcock, C. H.,
Ed.; Pergamon Press: Oxford, 1991; Vol. 2, pp 563-593. (b) Niimi, L.;
Shiino, K.; Hiraoka, S.; Yokozawa T. Tetrahedron Lett. 2001, 42, 1721.
(4) Danheiser, R. L.; Dixon, B. R.; Gleason, R. W. J. Org. Chem. 1992, 127,
8006 and references therein.
(5) Buckle, M. J. C.; Fleming, I.; Gil, S.; Pang, K. L. C. Org. Biomol. Chem.
2004, 45, 984 and references therein.
(6) Evans, D. A.; Aye, Y.; Wu, J. Org. Lett. 2006, 8, 2071.
(7) Evans, D. A.; Aye, Y. J. Am. Chem. Soc. 2006, 128, 11034.
(8) All propargylsilanes in this study were synthesized from commercially
available prop-2-ynol in three steps (see Supporting Information).
(9) See cif files in Supporting Information.
(10) Smadja, W. Chem. ReV. 1983, 83, 263.
(11) Sn(II)- and Al(III)[(R,R)-norephedrinepybox](OTf)3 returned 66% ee, 15%
yield (at 0 ïC), and 14% ee, 5% yield, respectively.
(12) Results using catalyst 1b: 90% ee, 19% yield (R ) Et); 91% ee, 13%
yield (R ) n-pent).
(13) The use of analogous triflate catalyst pre-prepared by the reaction of 1a
with Me2AlOTf led to decomposition pathways.
(14) Vinyl epoxide was recovered intact under the following conditions: TBAF,
THF (reflux), AcOH (neat, up to 100 ïC), HF‚pyridine (room temp).
(15) Allene geometry determined by Ag(I)-mediated stereospecific conversion
to dihydrofuran and subsequent 2DNOESY analysis. VanBrunt, M. P.;
Standaert, R. F. Org. Lett. 2000, 2, 705.
(16) We ascribed this unprecedented rearrangement to the steric bulk of the
[Si] hindering nucleophilic attack at the epoxide, instead promoting
formation of an “ate” complex. The hypervalent silyl species then
dissociates, with the σC-[Si] attacking the lowest energy acceptor orbital
(σ*C-O) to unveil the allenic alkoxide. The preferred antiperiplanar
alignment between C-[Si] and C-O was thought to give rise to the
observed stereochemical outcome. The azido silane thus generated then
acts as a source of eletrophilic [Si] to give O-t-BuPh2Si 12.
(17) With Br2, bromination of the phenyl rings was observed instead.
The derivatization of products initially afforded poor regio-
selectivity using standard carbanion additions. The bulky vinyl-
silicon function also emerged unscathed upon exposure to a range
of protodesilylation conditions.14 However, we were able to develop
two useful isomerization processes without loss of enantiomeric
purity (Scheme 2). For example, 10 was successfully converted
into the corresponding allenic alcohol 12 upon treatment with NaN3
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