Silver-catalyzed [2 + 2] cycloadditions of siloxy alkynes

Article abstract of DOI:10.1021/ja048251l

We have described the first [2 + 2] cycloadditions of siloxy alkynes with a range of unsaturated carbonyl compounds. The reactions are efficiently promoted by substoichiometric amount of silver trifluoromethanesulfonimide and display excellent regio- and diastereoselectivity combined with a broad substrate scope. Our studies have established unambiguously the stepwise mechanism of this process and provided evidence for a novel role of silver in the catalytic cycle of the reaction, which involves silver-based complexation and activation of siloxy alkyne toward the subsequent 1,4-addition. Copyright

Full text of DOI:10.1021/ja048251l

Published on Web 05/27/2004
Silver-Catalyzed [2 + 2] Cycloadditions of Siloxy Alkynes
Randy F. Sweis, Michael P. Schramm, and Sergey A. Kozmin*
UniVersity of Chicago, Department of Chemistry, 5735 South Ellis AVe, Chicago, Illinois 60637
Received March 26, 2004; E-mail: skozmin@uchicago.edu
Table 2. [2 + 2] Cycloadditions Catalyzed by AgNTf2 (5 mol %)
Silver-based catalysis is emerging as a novel paradigm in organic
synthesis leading to the development of an arsenal of mild and
efficient carbon-carbon bond-forming reactions1 and group-transfer
processes.2 In continuation of our systematic investigation of
reactivity of siloxy alkynes,3,4 we describe herein the discovery of
the first silver-catalyzed [2 + 2] cycloadditions of siloxy alkynes
with simple unsaturated ketones, esters, and nitriles. Efficiently
promoted by a catalytic amount of silver trifluoromethanesulfon-
imide, this transformation represents a new mode of reactivity of
siloxy alkynes5 and provides an efficient method for the assembly
of highly functionalized siloxy cyclobutenes. Our work is distin-
guished uniquely from the previously described thermal [2 + 2]
cycloadditions of ynamines,6 enantioselective Ti-promoted cyclo-
additions of alkynyl sulfides,7 and metal-catalyzed cycloadditions
of alkenes.8 Indeed, mild silver(I) catalysis is essential for its
compatibility with labile siloxy alkynes. Furthermore, we believe
that the reaction mechanism entails a silver-based activation of
siloxy alkyne toward subsequent 1,4-addition.
Our investigation began with an examination of reaction between
1-siloxy-1-hexyne 1 and enone 2 (Table 1). While no reaction was
observed under thermal conditions,9 the use of strong Lewis acids,
i.e., BF3 or TiCl4, resulted in formation of cyclobutene 3 with only
low efficiency (entries 2, 3), despite the previous successful studies
by Narasaka on [2 + 2] cycloadditions of alkynyl sulfides.7
Furthermore, only moderate improvement was achieved using
TIPSOTf and Sc(OTf)3 (entries 4, 5). Unexpectedly, our attempt
to generate TIPSNTf2 in situ (entry 6) resulted in the discovery of
10
AgNTf2 as an exceptional and unique promoter of [2 + 2]
cycloaddition between 1 and 2 (entry 8). The reaction proceeded
within minutes at 20 °C in CH2Cl2 in the presence of 5 mol % of
catalyst to furnish siloxy cyclobutene 3 in 90% isolated yield. The
efficiency was diminished employing other silver salts, i.e., AgOTf,
and AgSbF6 (entries 9, 10).
a
Refers to isolated yields of the silyl enol ethers that were fully
characterized by NMR, IR, and MS.
Our investigation of the scope of the present method is
summarized in Table 2. R,â-Unsaturated ketones, esters, and nitriles
reacted with siloxy hexyne 1 to give the corresponding siloxy
cyclobutenes 6-8 in 69-78% yield (entries 1-3). The use of
cyclohexenone afforded the corresponding [4.2.0]bicyclic silyl enol
ether 9 (entry 4). Additional studies revealed that aryl substitutions
in siloxy alkynes 4 and 5 were compatible with the general reaction
protocol (entries 5-9). Furthermore, the structure of siloxy cyclo-
butene 14 was confirmed by X-ray crystallography.
Subjection of E- and Z- crotonates 15 and 16 to siloxy alkyne 1
resulted in the formation of the same trans-substituted siloxy
cyclobutene 17 (Scheme 1). This outcome suggested for the first
time that the reaction proceeded via a stepwise mechanism. The
observed diastereoselection could be rationalized by considering
the minimization of the A1,3 strain in the two diastereomeric
transition states A and B. To provide additional support for the
stepwise mechanism of the [2 + 2] cycloaddition, and to rule out
the possibility of isomerization of Z-crotonate prior to the reaction,
we subjected a deuterated enone 18 (Z:E ) 92:8) to alkyne 1
Table 1. Initial Catalyst Evaluation
a
entry
catalyst (mol %)
none
BF3OEt2 (10)
TiCl4 (10)
Sc(OTf)3 (5)
TIPSOTf (10)
TIPSCl/AgNTf2 (5)
TIPSCl (10)
AgNTf2 (5)
solvent
temperature, °C
yield, %
1
2
3
4
5
6
7
8
9
CH3CN
CH2Cl2
CH2Cl2
CH3NO2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
80
-78
0
20
20
20
20
20
20
<5
17
28
58
62
80
<5
90
56
41
AgSbF6 (7)
AgOTf (10)
10
20
a Refers to isolated yields after chromatographic purification of the silyl
enol ether 3.
9
7442
J. AM. CHEM. SOC. 2004, 126, 7442-7443
10.1021/ja048251l CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Scheme 1
Figure 1. 500 MHz 1H NMR (A) and 125 MHz 13C NMR (B)
complexation experiments between siloxy alkyne 1 (0.1 M in CD2Cl2) and
AgNTf2 at 200 K.
Scheme 2
Scheme 3
based activation, distinguishes our findings from [2 + 2] cyclo-
additions of other heteroatom-functionalized alkynes and sets an
important precedent for broad investigation of reactivity of this
silver(I) catalyst.
Acknowledgment. We thank the Chicago Drug and Chemical
Association for undergraduate Award to R.F.S., and NIH Chemistry-
Biology Training Grant for predoctoral fellowship for M.P.S. S.A.K
thanks Amgen for a Young Investigator’s Award. S.A.K. is a fellow
of the Alfred P. Sloan Foundation. We thank Professor Yamamoto
and Professor He for helpful discussions.
Supporting Information Available: Full characterization of new
compounds and selected experimental procedures. This material is
available free of charge via the Internet at http://pubs.acs.org.
References
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reaction mechanism.11
Scheme 3 depicts two plausible mechanistic pathways, including
a classical LUMO-lowering Lewis acid activation of the enone (path
A), and silver-based activation of siloxy alkyne, followed by 1,4-
addition and trapping of the ketenium ion (path B). While the
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favor path B. We observed that treatment of a suspension of AgNTf2
in CH2Cl2 with siloxy alkyne resulted in formation of a homoge-
neous solution. Subsequent low-temperature NMR studies revealed
facile complexation of siloxy alkyne 1 with AgNTf2 even at -73
°C, as indicated by profound changes in 1H and 13C chemical shifts
of the alkyne (Figure 1).12 Addition of the enone 2 to this Ag-
alkyne complex resulted in rapid formation of product 3 within 1
min at -43 °C. Interestingly, a similar effect was not observed
using AgOTf, highlighting the importance of the counterion. In
contrast, addition of a stoichiometric amount of AgNTf2 to the
enone 2 at 20 °C results in only moderate changes in the NMR
spectrum. Furthermore, AgNTf2 did not efficiently catalyze [2 +
2] cycloadditions of enones with silyl enol ethers.13 These results
indicate that the catalytic role of AgNTf2 is most likely due to
complexation and activation of the siloxy alkyne toward subsequent
stepwise cycloadditon (path B).14
(4) For a recent review of ynolates, see: Shindo, M. Synthesis 2003, 2275.
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(10) For preparation of AgNTf2, see: Vij, A.; Zheng, Y. Y.; Kirchmeier, R.
L.; Shreeve, J. M. Inorg. Chem. 1994, 33, 3281.
(11) Control experiments indicated that no isomerization of either 16 or 18
occurred during their exposure to AgNTf2 for 30 min at 20 °C.
(12) For chemical shift changes upon complexation of alkynes and alkenes to
Ag(I) ions, see: Lewandos, G. S.; Gregston, D. K. Nelson, F. R. J.
Organomet. Chem. 1976, 118, 363.
(13) Takani, K.; Ueno, M.; Inanaga, K.; Ihara, M. J. Org. Chem. 2004, 69,
517 and references therein.
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Chem. Soc. 2003, 125, 3442 and references therein.
In summary, we have described the first silver-catalyzed [2 +
2] cycloadditions of silyl ynol ethers with a range of unsaturated
carbonyl compounds. The discovery of a unique AgNTf2 catalyst,
which promotes this transformation presumably via nucleophile-
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