Rhenium-Catalyzed Coupling of Propargyl Alcohols and Allyl Silanes

Full text of DOI:10.1021/ja039124c

Published on Web 12/02/2003
Rhenium-Catalyzed Coupling of Propargyl Alcohols and Allyl Silanes
Michael R. Luzung and F. Dean Toste*
Center for New Directions in Organic Synthesis, Department of Chemistry, UniVersity of California,
Berkeley, California 94720
Received October 19, 2003; E-mail: fdtoste@uclink.berkeley.edu
Table 1. Rhenium-Oxo-Catalyzed Synthesis of 1,5-Enynesa
Transition metal-catalyzed coupling of aryl and vinyl halides or
pseudohalides with organometallic nucleophiles has become an
important and powerful method for the formation of carbon-carbon
bonds.1 In contrast, related transition metal-catalyzed coupling reac-
tions of alkyl halides, for the formation of aliphatic carbon-carbon
bonds, are relatively rare.2 Addition of organometallic reagents to
propargylic halides/pseudohalides provides an attractive alternative
for the construction of sp3-sp3 C-C bonds. In addition to allowing
access to the saturated products by hydrogenation, the alkyne moiety
provides a handle for transformation into a variety of other func-
tional groups. Unlike transition metal-catalyzed allylic alkylation,3,4
propargylic substitution has been dominated by the reaction of
nucleophiles with propargyl cations stabilized by stoichiometric
transition metal complexes.5,6 We have recently reported that
rhenium(V)-oxo complex 1 serves as an air- and moisture-tolerant
catalyst for the formation of aliphatic ethers by the coupling of
simple alcohols and propargyl alcohols.7 Herein, we describe the
application of this catalyst system to the formation of carbon-
carbon bonds by the coupling of allylsilanes8 and propargyl alcohols.
Our preliminary attempts at rhenium-catalyzed coupling of
propargyl alcohols and allyl trimethylsilane were complicated by
competing Meyer-Schuster rearrangement.9 Gratifyingly, we found
that 5 mol % (dppm)ReOCl3 (1) and 5 mol % ammonium
hexafluorophosphate in nitromethane, at 65 °C, cleanly produced
the substituted 1,5-enyne in excellent yields (Table 1) and without
competing rearrangement to the enone. The reaction could be carried
out with lower catalyst loadings (compare entries 1 and 2) without
significant deterioration in yield by increasing the reaction tem-
perature to 80 °C. Similarly, the reaction temperature could be
lowered to room temperature (compare entries 5 and 6) by extending
the reaction time from 2 to 8 h. Substitution was carried out on
electron-rich and electron-poor (entry 9) aromatic substrates.
Halogenated aromatic substrates (entries 9-11) that may subse-
quently participate in transition metal-catalyzed cross-coupling
reactions and acid labile ketals (entries 10 and 11) survive the
reaction conditions. Sterically encumbered ortho-disubstituted phen-
a Reaction conditions: 0.25 M propargyl alchohol in MeNO2, 3.0 equiv
yl groups (entry 12) do not affect the course of the carbon-carbon
bond formation. Notably, substitution of a propargyl alcohol occurs
preferentially to reaction with a propargyl aryl ether (entry 15).
Variation of the alkynyl substituent is also well tolerated; however,
larger alkynyl substituents require slightly longer reaction times,
but maintain high yields. Additionally, chemoselective propargylic
substitution occurs in preference to conjugate addition, when an
alkynoate ester is employed as a substrate (entry 7).
of allylsilane, 2 h. b Isolated yield after chromatography.
cocatalyst (eq 1). Rhenium-catalyzed coupling with tertiary alcohol
2a allows for the construction of a quaternary carbon without com-
peting formation of the allene product.10 Secondary aliphatic alcohol
2b also participates in our rhenium-catalyzed reaction, albeit with
diminished yield.
The stability of our high oxidation state complexes allows for
catalyst recovery in some cases (eq 2). For example, coupling of 4
and allyltrimethylsilane, catalyzed by 5 mol % 1, affords the desired
adduct (5) in 96% yield. Approximately 70% of the initial catalyst
was recovered by removal of MeNO2 in vacuo, followed by
precipitation of the catalyst with hexanes or ether. After filtration
of the solid, NH4PF6 was removed from the catalyst by a simple
aqueous wash. The recovered rhenium complex can be reused in
the coupling reaction without a noticeable deterioration in activity.
Nonbenzylic propargyl alcohols also participate in the substitution
reaction; however, silver hexafluoroantimonate is required as the
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10.1021/ja039124c CCC: $25.00 © 2003 American Chemical Society

C O M M U N I C A T I O N S
range of silanes and propargyl alcohols, including simple aliphatic,
are viable coupling partners. Additionally, rhenium-catalyzed reac-
tion of chiral crotylsilanes allows for the enantioselective synthesis
of two adjacent stereocenters. The catalyst is both air and moisture
stable, allowing for the recovery and reuse of the rhenium complex.
This exemplifies the potential and advantages of high oxidation
transition complexes as catalysts for organic reactions.
We also examined the effect of variation in the allylsilane. For
example, chloromethyl-substituted allylsilane participated well in
the reaction (Table 1, entry 8). Additionally, the diastereoselectivity
of the substitution was investigated using enantioenriched crotyl-
silane 6 as the nucleophile. In temperatures ranging from 50 to 65
°C, our rhenium-catalyzed coupling consistently afforded propargyl
adduct 7 as a 1.2:1 mixture of diastereomers with complete fidelity
in the chirality transfer (eq 3). The presence of ortho-dimethyl
groups on the aryl ring significantly increased the diastereoselec-
tivity (eq 4). Rhenium-catalyzed coupling of (E)- and (Z)-crotyl-
silanes (9),11 at room temperature, produced 10 and ent-1012 in
>10:1 dr and 7:1, respectively.
Acknowledgment. We gratefully acknowledge the University
of California, Berkeley, the Camille and Henry Dreyfus Foundation,
Research Corporation, Merck Research Laboratories, Amgen Inc.,
and Eli Lilly & Co. for financial support. The Center for New Direc-
tions for Organic Synthesis is supported by Bristol-Myers Squibb
as a Sponsoring Member and Novartis Pharma as a Supporting
Member.
Supporting Information Available: Experimental procedures and
compound characterization data (PDF). This material is available free
of charge via the Internet at http://pubs.acs.org.
References
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To establish the absolute and relative stereochemistry of the coup-
ling of propargyl alcohols with chiral allylsilanes, we undertook a
synthesis of δ-lactone, 7,8-di-O-methylcalopin (15) (Scheme 1).13
Two of the three stereocenters in 15 were set by the rhenium-
catalyzed allylation of propargyl alcohol 11 with chiral allyl silane
12.14 Ozonolysis of the major diastereomer followed by reductive
workup and then protection gave protected alcohol 13 in 68% yield
over three steps. Desilylation and hydrogenation of the acetylene
to the olefin allowed for installation of the C1-C2 oxygens by di-
hydroxylation. The hydroxyl groups were differentiated by forma-
tion of the para-methoxybenzyl acetal followed by regioselective
reduction with Dibal-H to afford 14. Oxidation of the primary
alcohol with Dess-Martin periodinane and deprotection of the silyl
ether provided a lactol that was oxidized to the lactone using
catalytic TPAP and NMO. Deprotection of the PMB ether afforded
(-)-7,8-di-O-methylcalopin 15, whose stereochemistry was assigned
from nOe measurements and comparison of the optical rotation.13,15
In conclusion, we have developed the first transition metal-
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Scheme 1. Synthesis of (-)-Di-O-Me-calopina
(10) Rhenium-catalyzed reaction with 1,1-diphenylpropan-1-ol produced the
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a (a) 5 mol % (dppm)ReOCl3, 5 mol % NH4PF6, CH3NO2, 82% (1.2:1
dr); (b) O3, MeOH, then NaBH4; (c) TBDMS-Cl, imidazole, 68% over
two steps; (d) K2CO3, MeOH, quant.; (e) H2, cat. Pd(BaSO4), quinoline,
quant.; (f) cat. OsO4, NMO, 69% (1.2:1 dr); (g) (MeO)2CHC6H4-p-OMe,
PPTS; (h) Dibal-H, CH2Cl2, 73% over two steps; (i) Dess-Martin
periodinane, 80%; (j) TBAF, CH2Cl2; (k) 5% TPAP, NMO, 4 Å MS,
CH2Cl2, 66% over two steps; (l) H2, Pd-C, EtOH, 49%.
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