Lewis acid promoted carbon-carbon bond cleavage of γ-silyloxy-β- hydroxy-α-diazoesters

Article abstract of DOI:10.1021/ja801004d

Cyclic γ-silyloxy-β-hydroxy-α-diazoesters undergo efficient rupture of the C_β-C_γ bond when treated with tin tetrachloride to provide tethered aldehyde ynoate products in high yield. Copyright

Full text of DOI:10.1021/ja801004d

Published on Web 03/06/2008
Lewis Acid Promoted Carbon-Carbon Bond Cleavage of
γ-Silyloxy-â-hydroxy-r-diazoesters
Cristian Draghici and Matthias Brewer*
The UniVersity of Vermont, Department of Chemistry, 82 UniVersity Place, Burlington, Vermont 05405
Received February 8, 2008; E-mail: Matthias.Brewer@uvm.edu
Table 1. Tin Tetrachloride Mediated Ring Fragmentation of
Chemical reactions that result in the fragmentation of carbon-
γ-Silyloxy-â-hydroxy-R-diazoesters
carbon bonds are important transformations because they often
unmask latent functional groups under chemoselective reaction
conditions. Ring fragmentations are particularly useful because they
result in two newly formed functional groups tethered at a
predefined distance determined by the ring size. Fragmentations
are not always obvious retrosynthetic disconnects, but they can
efficiently provide functionalized synthetic intermediates.1-3 Im-
portant examples of these transformations include the oxidative
cleavage of 1,2-diols and the ozonolysis of olefins to provide
tethered dicarbonyl compounds,4-6 the Grob fragmentation to
provide tethered alkenyl ketones,2,7 and the Eschenmoser-Tanabe
fragmentation to provide tethered alkynyl ketones.8,9 A more
efficient route to tethered alkynyl ketones was recently reported
by Dudley and co-workers in which nucleophiles induce the
fragmentation of vinylogous acyl triflates.10
Herein we report that γ-silyloxy-â-hydroxy-R-diazoesters (e.g.,
4, Scheme 2) undergo efficient rupture of the Câ-Cγ bond when
treated with Lewis acids to provide an aldehyde and an ynoate
product. When the Câ-Cγ bond is contained in a ring, tethered
aldehyde ynoates are formed. Tethered aldehyde ynoates are
versatile synthetic intermediates,11 and this functional group
combination is unique to this fragmentation.
We first observed this bond fragmentation during work with
R-diazoester 1 (Scheme 1). The reaction of R-diazoester 1 with
indium(III) triflate provided a complex mixture of products from
which ethyl 3-phenylpropiolate (2) was isolated in 17% yield. The
formation of propiolate 2 appeared to involve loss of the â-silyloxy
group, loss of molecular nitrogen, and fragmentation of the Câ-
Cγ bond.
Scheme 1. Initial Observation of C-C Bond Fragmentation
To explore the possibility of utilizing this unprecedented reactiv-
ity in a ring fragmentation reaction we prepared γ-silyloxy-â-
hydroxy-R-diazoester 4 (Scheme 2).12 Species of this type are easily
prepared by the addition of ethyl lithiodiazoacetate to the corre-
sponding ketone precursor.13,14 We were pleased to find that treating
diazoester 4 with freshly dried indium triflate resulted in observable
gas evolution and provided ethyl 8-oxooct-2-ynoate (5) as the only
observable product.
Scheme 2. Preparation and Ring Fragmentation of a
γ-Silyloxy-â-hydroxy-R-diazoester
Preliminary optimization of the reaction conditions indicate that
freshly dried indium triflate and freshly distilled tin tetrachloride
provide the best results. Older batches of tin tetrachloride provided
more complex product mixtures as did BF3‚OEt2, MgBr2‚OEt2,
scandium triflate, titanium tetrachloride, and anhydrous HCl.
Dibutyl tin dichloride failed to promote the reaction. Due to the
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J. AM. CHEM. SOC. 2008, 130, 3766-3767
10.1021/ja801004d CCC: $40.75 © 2008 American Chemical Society

C O M M U N I C A T I O N S
Scheme 3. Proposed Mechanism
Acknowledgment. This work is dedicated to Prof. Larry
Overman on the occasion of his 65th birthday. We thank Dr. John
Greaves (University of California, Irvine) for obtaining mass
spectral data and Dr. P. Bruce Deker (University of Vermont) for
assistance with NMR characterization. Financial support from the
University of Vermont, the Vermont Experimental Program to
Stimulate Competitive Research (Grant No. EPS0236976), and
Amgen is gratefully acknowledged. Acknowledgment is made to
the Donors of the American Chemical Society Petroleum Research
Fund for partial support of this research.
Supporting Information Available: Experimental procedures and
spectroscopic data for all new compounds. This material if available
free of charge via the Internet at http://pubs.acs.org.
limited solubility of indium triflate in CH2Cl2, tin tetrachloride was
chosen as the Lewis acid of choice for further studies. Reducing
the quantity of tin tetrachloride to 10 mol % promoted the
fragmentation reaction, but product yield was reduced. Changing
the solvent from CH2Cl2 to toluene had little effect on the reaction,
whereas DMF inhibited the reaction completely.
References
(1) For reviews concerning ring fragmentations, see: (a) Hendrickson, J. B.
J. Am. Chem. Soc. 1986, 108, 6748-6756. (b) Grob, C. A.; Schiess, P.
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To test the generality of this ring fragmentation we prepared
several additional γ-silyloxy-â-hydroxy-R-diazoesters (Table 1); this
reaction appears to be quite general. Tin mediated fragmentation
of cyclohexanone derivative 4 provided ethyl 8-oxooct-2-ynoate
(5) in 94% yield while 1-tetralone derivative 6 and 1-indanone
derivative 8 provided the corresponding homologous aryl-substituted
ynoates 7 and 9 in 95% and 71% yield, respectively.15 The more
highly conjugated (Z)-ethyl 8-oxooct-4-en-2-ynoate (11) was formed
in 97% yield from cyclohexenone derivative 10.16 The easily
separable diastereomeric cycloheptanone derivatives 12 and 14 were
formed in a 1 to 2.8 ratio, and these fragmented to ethyl 9-oxonon-
2-ynoate (13) in 91% and 76% yield, respectively. Dehydroisoan-
drosterone derivative 15 fragmented to provide the desired ynoate
aldehyde 16 in 76% yield.17 This example is notable because the
steroid-derived product would not be straightforward to prepare
by other means. Finally, the 2-methyl-2-silyloxycyclohexanone
derivative 17 fragmented to the tethered ketone ynoate 18 in only
27% yield.18
Our current mechanistic hypothesis for this transformation is
based on Padwa et al.’s19 report that â-hydroxy-R-diazoesters react
with BF3‚OEt2 to provide vinyl diazonium species, and ultimately
vinyl cations, via elimination of the â-hydroxyl group. We
hypothesize that γ-silyloxy-â-hydroxy-R-diazoesters react similarly
with tin tetrachloride to provide vinyl diazonium 19 (Scheme 3) in
which the Câ-Cγ bond and the C-N bond are coplanar. As
molecular nitrogen leaves, lone pair donation from the γ-oxygen
atom would result in Câ-Cγ bond fragmentation to provide ynoate
20. Subsequent loss of the tert-butyldimethylsilyl group would
provide tethered aldehyde ynoate 5.
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(12) The relative configuration of diol 4 was established through 2D NMR
analysis.
(13) (a) Schoellkopf, U.; Frasnelli, H. Angew. Chem., Int. Ed Engl. 1970, 9
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(15) Compounds 6 and 8 were obtained as 10:1 mixtures of diastereomers.
(16) Hydrogenation of compounds 10 and 4 over Pd/C provides identical
saturated products and confirms the cis-diol stereochemistry of 10.
(17) The relative stereochemistry of 15 was established through 2D NMR
analysis.
(18) Diazo 17 was isolated as an inseparable mixture of diastereomers.
(19) Pellicciari, R.; Natalini, B.; Sadeghpour, B. M.; Marinozzi, M.; Snyder,
J. P.; Williamson, B. L.; Kuethe, J. T.; Padwa, A. J. Am. Chem. Soc.
1996, 118, 1-12.
The Lewis acid promoted fragmentation of γ-silyloxy-â-hydroxy-
R-diazoesters provides a simple and efficient way to prepare tethered
aldehyde ynoates with varying tether length. Further studies on the
scope and mechanism of this fragmentation and synthetic applica-
tions of the tethered aldehyde ynoate products are underway.
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