Formation and utility of oxasilacyclopentenes derived from functionalized alkynes

Article abstract of DOI:10.1021/ja047498f

Oxasilacyclopentenes were shown to be synthetically useful masked allylic alcohols constructed in high yields and regioselectivities from terminal and internal alkynes. Several functional groups were shown to be tolerated utilizing silver-catalyzed silacy

Full text of DOI:10.1021/ja047498f

Published on Web 07/20/2004
Formation and Utility of Oxasilacyclopentenes Derived from
Functionalized Alkynes
Timothy B. Clark and K. A. Woerpel*
Department of Chemistry, UniVersity of California, IrVine, California 92697-2025
Received April 29, 2004; E-mail: kwoerpel@uci.edu
Table 1. Silacyclopropenation of Alkynes (Eq 1)
Reductive coupling reactions of alkynes with ketones and alde-
hydes represent powerful methods for the synthesis of functionalized
allylic alcohols from simple starting materials.1-7 While these reac-
tions are typically accomplished using transition metal promoters,
we envisioned that the use of silicon in the coupling of carbonyls
to alkynes would provide intermediate oxasilacyclopentenes which
could then be unmasked to form allylic alcohols. Silacyclopropenes,
prepared from alkynes,8 undergo insertion reactions with carbonyl
compounds to form oxasilacyclopentenes,9 which would serve as
masked allylic alcohol derivatives (Scheme 1). This process would
form cyclic vinylsilanes that are available for further functional-
ization, including oxidation of the carbon-silicon bond,10 expanding
the transformation scope beyond the preparation of allylic alcohols.
In this Communication, we describe a mild method for the synthesis
of silacyclopropenes from functionalized alkynes and demonstrate
that these reactive compounds can be converted, without isolation,
to oxasilacyclopentenes with high regioselectivity. Further trans-
formations of these products occur diastereoselectively, leading to
the assembly of a number of architecturally diverse products.
a As determined by 1H NMR spectroscopic analysis of the product relative
to an internal standard (PhSiMe3). b The reaction mixture was heated in a
sealed NMR tube at 80 °C (2e) or 50 °C (2g).
Scheme 1. Formation of Oxasilacyclopentenes from Alkynes
Table 2. One-Flask Silacyclopropenation/Carbonyl Insertions of
Phenylacetylene (Eq 2)
We initially developed the metal-catalyzed silacyclopropenation
of a range of functionalized alkynes.8,11 Utilizing Ag3PO4 as cata-
lyst,12 high yields of disubstituted silacyclopropenes were achieved
with internal alkynes (Table 1, entries 1, 2, 6). Terminal alkynes,
which are normally difficult substrates for silylene transfer,13,14 also
provided high yields of the desired silacyclopropenes (entries 3-5,
7-8). Propargyl ethers and amines also participate in this reaction
(entries 5-8). In addition, selective silacyclopropenation to an
alkyne in the presence of an olefin was achieved (entry 8).15
Because silacyclopropenes are highly reactive and difficult to
isolate,9 an in situ procedure for the functionalization of these
intermediates was developed. The use of CuBr2 as the insertion
catalyst proved to be optimal. Reactions of saturated and unsaturated
aldehydes and ketones provided high yields and regioselectivities
(eq 2, Table 2).16 In all cases, copper-catalyzed ring expansion
resulted from insertion into the more substituted C-Si bond of the
silacyclopropene. Selectivity likely arises from disfavored interac-
tions between the silacyclopropene substituent and the t-Bu groups
upon insertion into the less substituted C-Si bond.17
a Isolated yield from phenylacetylene after purification by flash chro-
matography. b As determined by GCMS analysis of the unpurified product
mixture. c As determined by 1H NMR spectroscopic analysis of the
unpurified product mixture.
additional functionality, such as a propargylamine (Table 3, entry
2), were tolerated under the optimized conditions.
The scope of the one-flask formation of oxasilacyclopentenes
from internal and terminal alkynes was explored with acetophenone
and butyraldehyde (eq 3, Table 3). While CuI provided increased
yields for terminal alkynes (entries 1 and 2), Cu(OTf)2 proved to
be the best catalyst for formation of insertion products derived from
internal alkynes (Table 3, entries 3-5). Alkynes containing
Transformations involving the vinylsilane functionality of the
oxasilacyclopentene were explored, displaying the synthetic ver-
satility of these intermediates. Simple removal of the t-Bu2Si moiety
by protodesilylation of oxasilacyclopentene 6a afforded highly
substituted allylic alcohol 8 (eq 4). This regioisomer is typically-
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10.1021/ja047498f CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Table 3. One-Flask Silacyclopropenation/Carbonyl Insertions of
Various Alkynes (Eq 3)
Diels-Alder adduct 13 as a 99:1 mixture of diastereomers favoring
the exo adduct (vide infra). Although the exo-selective Diels-Alder
was not expected to give high facial selectivity with a chiral
oxasilacyclopentene such as 12, 4:1 diastereoselectivity was
achieved upon thermal cycloaddition with N-phenylmaleimide.21
The formation of adduct 14 represents a cyclohexene core with
five stereogenic centers. We propose that the endo transition state
in these reactions was disfavored due to steric interactions between
the dienophile and the t-Bu groups on silicon.
In conclusion, alkynes can be transformed into synthetically
valuable masked allylic alcohols through the in situ functionalization
of silacyclopropenes. The potential synthetic utility of the inter-
mediate oxasilacyclopentenes was demonstrated through the Diels-
Alder reactions to provide highly substituted carbocycles 13 and
14.
Acknowledgment. This research was supported by the National
Institute of General Medical Sciences of the National Institutes of
Health (GM54909). K.A.W. thanks Merck Research Laboratories
and Johnson & Johnson for awards to support research. We thank
Dr. Phil Dennison for assistance with NMR spectrometry, Dr.
Joseph W. Ziller for X-ray crystallography, and Dr. John Greaves
and Dr. John Mudd for mass spectrometry.
Supporting Information Available: Experimental procedures;
spectroscopic, analytical, and X-ray data for the products (PDF, CIF).
This material is available free of charge via the Internet at http://
pubs.acs.org.
a Insertions provided g95:5 regioselectivity, except 5 (90:10), as
determined by GC analysis of the unpurified product mixture. b Isolated
yield from alkyne after purification by flash chromatography.
challenging to obtain using other methods.18
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The alkene moiety of the oxasilacyclopentene was also reactive.
Hydrogenation of the oxasilacyclopentene, followed by oxidation10
of the resulting oxasilacyclopentane, provided 1,3-diol 9 diaste-
reoselectively. The observed diastereomer may have resulted from
addition of hydrogen to the face opposite the pseudoaxial t-Bu group
(TS-A, Scheme 2).19,20
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Scheme 2
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(12) As Ag3PO4-catalyzed silacyclopropenation provides intermediates that are
difficult to isolate, thermal silacyclopropenation was used to characterize
products. Details are provided as Supporting Information.
(13) To date, only one other example of a silacyclopropene generated from a
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Upon establishing the reactivity of simple oxasilacyclopentenes,
we utilized the olefin to increase the molecular complexity through
a cycloaddition reaction. Oxasilacyclopentenes 11 and 12 were
constructed using typical conditions (vide supra) utilizing enyne
10 (eq 5). Heating diene 11 with N-phenylmaleimide provided the
(15) Calculations of the thermodynamic energies of silacyclopropenes and
silacyclopropanes suggest ring strain is decreased in silacyclopropenes:
(a) Gordon, M. S. J. Am. Chem. Soc. 1980, 102, 7419-7422. (b) Goller,
A.; Heydt, H.; Clark, T. J. Org. Chem. 1996, 61, 5840-5846.
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(20) Fehr, C. Angew. Chem., Int. Ed. 1998, 37, 2407-2409.
(21) Details are provided as Supporting Information.
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