Cyclopropenation of alkylidene carbenes derived from α-silyl ketones

Article abstract of DOI:10.1021/ja101998w

A new cyclopropanation reaction involving Cα-Si bond insertion of alkylidene carbenes derived from α-silyl ketones has been developed. This unprecedented alkylidene carbene reactivity features excellent selectivity for insertion into Cα-Si bonds rather than insertion into Cγ-H bonds or addition to,δ-double or -triple bonds. The selectivity trend clearly indicates that the α-oxygen in the tether significantly promotes Cγ-H insertion, although the Cα-Si bond insertion still competes effectively.

Full text of DOI:10.1021/ja101998w

Published on Web 04/22/2010
Cyclopropenation of Alkylidene Carbenes Derived from r-Silyl Ketones
Jingwei Li,† Chunrui Sun,† and Daesung Lee*
Department of Chemistry, UniVersity of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607-7061
Received March 9, 2010; E-mail: dsunglee@uic.edu
Table 1. Formation of Cyclopropenes via CR-Si Bond Insertion of
Alkylidene Carbenes Derived from R-Silyl Ketonesa
Insertion of alkylidene carbenes into C-H bonds is a powerful
tool for constructing carbocycles containing quaternary carbon
centers with defined stereochemistry.1 We envisioned that the
prowess of this C-H insertion reaction can be extended to the silyl-
substituted alkylidene carbene A, which should constitute an
effective entry into the synthesis of functionalized cyclopentene
derivatives of type B. In a preliminary study, however, we found
that alkylidene carbene A preferentially provided cyclopropene C
instead of cyclopentene derivative B, except for substrates with
strongly activated Cγ-H bonds.2 This is probably due to a more
favorable interaction of the empty p orbital of the carbenic carbon
with the nearby C-Si bond than with the rather remote Cγ-H
bond. Since cyclopropenes are unusual yet versatile substrates for
a variety of synthetic transformations,3 the development of efficient
methods for their preparation is highly desirable. Herein we report
a new cyclopropenation that involves selective insertion into the
CR-Si bond of R-silyl ketones.
Our investigation commenced with a search for an efficient method
for the preparation of R-silyl ketones.4 We found that the indium
chloride-catalyzed reaction between trimethylsilyldiazomethane and
aldehydes provided an efficient preparation of R-silyl ketones (condition
A in Scheme 1).5 With this secure method, citronellal 1a was converted
into 2a, which was then treated with lithiated trimethylsilyldiaz-
omethane6 without purification (condition B in Scheme 1), delivering
a product in 77% yield. To our surprise, the identity of this compound
was established to be silylcyclopropene 3a,7 and the expected
cyclopentene derivative 4a was not detected.
Scheme 1. Selective Insertion into the CR-Si Bond Rather Than
the Cγ-H Bond
a Conditions A and B are shown in Scheme 1. b Isolated yield.
unsaturation (1b-i) and branched chains (1j-m) with electronic
and steric variation (Table 1). Both cis- and trans-dodecenal (1b
and 1c) afforded the corresponding cyclopropenes 3b and 3c in 81
and 78% yield (entries 1 and 2). Symmetrical cis-dialdehyde8 1d
also gave the corresponding biscyclopropene 3d in good yield (entry
3). Aldehydes 1e-g with trisubstituted γ,δ-double bonds behaved
similarly, affording cyclopropenes 3e-g in good yields (entries
4-6). An alkyne or aromatic substituent at this position in 1h and
1i did not interfere with the CR-Si insertion, which provided 3h
and 3i in 54 and 65% yield, respectively. Although the addition of
alkylidene carbenes to γ,δ-double bonds is well-precedented,9 the
addition reaction was not observed with these systems. The
The generality of cyclopropene formation via CR-Si insertion
was further examined using a variety of aldehydes with γ,δ-
† These authors contributed equally.
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10.1021/ja101998w  2010 American Chemical Society

C O M M U N I C A T I O N S
selectivity of insertion into the Cγ-H bond versus the CR-Si bond
was also examined with aldehydes 1j-m10 containing methylene
and methine protons as well as an oxygen atom at the Cγ position.1c
Quite surprisingly, no competing insertion into insertion into the
Cγ-H protons or oxygen moiety11 was observed, and only
cyclopropenes 3j-m were isolated in good yields.
reactivity features an excellent selectivity for CR-Si bond insertion
rather than Cγ-H bond insertion or addition to γ,δ-double or -triple
bonds. The selectivity trend in Table 2 clearly indicates that the
R-oxygen in the tether significantly promotes Cγ-H insertion,
although the CR-Si bond insertion still competes effectively. It is
noteworthy that the reactivity of the C-H bond toward carbene
insertion depends intricately on electronic and steric factors and
cannot be predicted by the simple additive effect of contributing
factors.
Next, a variety of substrates carrying more strongly activated
Cγ-H bonds were explored (Table 2). Because of the especially
strong activating role of the R-oxygen in the tether for Cγ-H
insertion,1c the formation of both cyclopropene 3 via CR-Si bond
insertion and dihydrofuran 4 via Cγ-H insertion were expected.
When subjected to condition A followed by condition B, aldehyde
1n with Cγ-methylene protons provided a mixture of cyclopropene
3n and allylic silane-containing dihydrofuran 4n in a 1.2:1 ratio in
75% yield (entry 1). Similarly, aldehyde 1o afforded a mixture of
cyclopropene 3o and C-H insertion product 4o in a slightly higher
ratio (2.4:1) in 84% yield (entry 2). Surprisingly, aldehyde 1p with
allylic methylene protons yielded cyclopropene 3p and C-H
insertion product 4p in only a 2:1 ratio, despite the fact that allylic
C-H bonds are generally more activated toward carbene insertion
(entry 3). The effect of an alkyl substituent was examined using
methine-proton-containing substrate 1q, which, contrary to our
expectation, provided an even higher ratio (3.2:1) of cyclopropene
3q to C-H insertion product 4q (entry 4). Substrate 1r containing
a methine proton on a six-membered ring provided cyclopropane
3r and a slightly increased relative amount of insertion product 4r
(3r/4r ratio of 1.5:1) in 69% yield (entry 5).
Acknowledgment. We thank UIC and the donors of American
Chemical Society Petroleum Research Fund for financial support
of this work. The mass spectrometry facility at UIUC and Mr.
Furong Sun are greatly acknowledged.
Supporting Information Available: General procedures and char-
acterization data for representative compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
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Table 2. Selectivity for Cyclopropenation of R-Silyl Ketones
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In conclusion, we have developed a new cyclopropenation
reaction involving CR-Si bond insertion of alkylidene carbenes
derived from R-silyl ketones. This unprecedented alkylidene carbene
JA101998W
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