Brummond et al.
JOCArticle
of alkylidenecyclopentenones including bicyclo[5.3.0]undec-
adienones, a long-sought-after ring system previously
inaccessible to cyclocarbonylation methodologies.9 It was
hypothesized that a Rh(I)-catalyzed cyclocarbonylation
reaction of allenol acetates affording R-acetoxy cyclopentadie-
nones may be possible due to the mildness of the reaction
conditions and the unlikely prospect of the rhodium(I) catalyst
participating in a single electron transfer process under these
reaction conditions.10 Moreover, allenol acetates are well-
known and are prepared via a formal [3,3]-sigmatropic re-
arrangement of a propargyl acetate using a variety of transi-
tion-metal catalysts such as Ag, Au, Cu, Pt, and Rh.11 Thus,
readily available allenol acetates afford an opportunity to
directly access R-acetoxy cyclopentadienones, which in turn
can be used as precursors to R-hydroxycarbonyl-containing
compounds. Herein, a Rh(I)-catalyzed cyclocarbonylation
reaction to form R-acetoxycyclopentadienones is reported.
SCHEME 2. Preparation of Propargyl Acetates 7a-f
Results and Discussion
Substrate Design. Once the feasibility of the cyclocarbony-
lation reaction of allenol acetates to produce R-acetoxy carbo-
nyls has been established, our research objective is to examine
several cycloaddition substrates. Guided by a plethora of
natural product substructures that would benefit from this
reaction: (1) the chain length of the tether between the allene
and alkyne will be varied (n = 1-4); (2) substitution on the
allene, alkyne and tether altered; and (3) stereochemical con-
sequences of the [3,3]-sigmatropic rearrangement of 1 to give 2
and the cyclocarbonylation reaction to give 3 will be examined
(Scheme 1). Furthermore, imbedding the allene into a con-
formationally anchored cyclohexane ring will serve as an
effective method for examining diastereoselectivity issues.
halides or triflates 5a-c (Scheme 2).12 Acidic hydrolysis with
oxalic acid gave ketones 6a and 6c (n = 1, 3) in 44% and 83%
yield.13 Ketone 6b was obtained in only 5% yield, possibly due
to a competing E2 elimination of the triflate to form an enyne.
The diastereomers of 6a-c were separated via column chro-
matography, and the major diastereomer was carried forward.
Addition of ethynyl or 1-propynylmagnesium bromide to
6a-c gave the corresponding propargyl alcohols in 63-90%
yields with diastereoselectivities ranging from 1:1 to 3:1. The
major diastereomers were assigned on the basis of the predis-
position of small nucleophiles to add axially to substituted
cyclohexanones.14 Separation of the two diastereomers was
readily accomplished via column chromatography. The major
diastereomers were acetylated using triethylamine, DMAP,
and acetic anhydride yielding a single diastereomer of propar-
gyl acetates 7a-d in 39-47% yield from ketones 6a-c. Two
substrates were prepared to examine electronic and steric
effects of the carboxy group. A bulky pivaloyl group was
appended to the corresponding propargyl alcohol from 6c
using trimethylacetic anhydride and catalytic Sc(OTf)3 to give
7e in 82% yield.15 An electron-withdrawing p-nitrobenzoate
was attached to the same propargyl alcohol using 4-nitroben-
zoyl chloride and DMAP to give 7f in 74% yield.16
SCHEME 1. Substrate Design
Preparation of Propargyl Acetates. Propargyl acetates were
prepared using two general procedures. Preparation of cyclo-
hexane-based substrates began by alkylating the lithium
enolate of dimethyl hydrazone 4, with the corresponding
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Linear propargyl acetates were prepared using two differ-
ent methods (Scheme 3). Propargyl acetates 9a-d (n = 1, 2)
were prepared by addition of ethynylmagnesium bromide or
1-propynylmagnesium bromide to aldehyde 8a or ketones
8b,c followed by in situ acetylation with acetyl chloride
furnishing the desired products in 55-83% yields.17 For
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