Group-selective ring-closing enyne metathesis: Concentration-dependent selectivity profile of alkynylsilyloxy-tethered dienynes

Article abstract of DOI:10.1021/ja046043n

Highly group-selective ring-closing metathesis of alkynylsilyloxy-tethered dienynes was achieved by using Grubbs first- and second-generation catalyst. The remarkable selectivity increase at higher concentration for differentiating between two alkene moie

Full text of DOI:10.1021/ja046043n

Published on Web 09/09/2004
Group-Selective Ring-Closing Enyne Metathesis: Concentration-Dependent
Selectivity Profile of Alkynylsilyloxy-Tethered Dienynes
Sarah V. Maifeld, Reagan L. Miller, and Daesung Lee*
Department of Chemistry, UniVersity of Wisconsin, Madison, Wisconsin 53706
Received July 2, 2004; E-mail: dlee@chem.wisc.edu
Table 1. RCM of Symmetric and Sterically Differentiated
Enyne metathesis is a powerful carbon-carbon bond-forming
Dienynesa
reaction capable of constructing 1,3-dienes.1 With multiple pathways
and products possible in enyne ring-closing metathesis (RCM)
reactions, site-selective initiation by the catalyst (1 or 2)2 seems
necessary for selectivity.3 Although the selective initiation can be
achieved by modifying the reactivity of the alkene or alkyne
moieties with steric and stereoelectronic factors, in many cases,
the implementation of these factors requires extra synthetic
manipulations.4 Irrespective of the selectivity in the initiation,5 a
highly selective enyne RCM reaction can still be realized if the
pre-ring-closure steps are reversible and occur at higher rates than
that of the ring-closure step. As shown in Scheme 1, alkynylsilyl-
Scheme 1
a A solution of catalyst 2 (7.5 mol %) and substrate in CH2Cl2 (0.001
M) was heated to reflux for 30 min. b Isolated yield. c 2 equiv of 10 under
reflux for 4 h. d Mixture of trans- and cis-isomers (6:1)
Scheme 2
oxy-tethered dienyne 3,6,7 which possesses nonsymmetrically
tethered alkenes in nearly equivalent steric and stereoelectronic
environments, would generate intermediates 4 and 5 in roughly
equal amounts when catalyzed by 1 or 2. If the steric hindrance of
the silylalkynyl moiety slows the ring-closure rate as compared to
the alkylidene exchange between 4 and 5 (kexchange . kS and kL), a
pre-equilibrium situation arises in which a relatively faster ring-
closure rate for the smaller-sized ring (kS) over that of the larger
one (kL) would preferentially generate 6 over 7 (kS > kL). We report
herein a new type of group-selective enyne RCM reaction of
alkynylsilyloxy-tethered dienyne 3 and its concentration-dependent
selectivity profile.
To obtain information for a general reactivity profile of silyl-
substituted enynes8 and to address the potential difficulty in
differentiating similar product structures (e.g., 6 vs 7) derived from
the RCM of alkynylsilyloxy dienyne 3, we generated a spectroscopic
standard of siloxacycles9 from symmetrical and sterically well-
differentiated bisalkene-containing substrates 8a-e (Table 1).
Regardless of the tether sizes, rapid enyne RCM occurred without
interference of diene RCM, providing excellent yields of the cyclic
1,3-diene products 9a-e. Notably, the chemical shifts of the
endocyclic vinyl proton Hâ exhibit a distinctive dependency on the
ring size. For substrates showing a high tendency to dimerize after
the initial enyne RCM, an external alkene (10; cis-AcOCH2CHd
CHCH2OAc) was added to the reaction, thereby retarding dimer-
ization and yielding a product resulting from enyne RCM followed
by cross metathesis (CM) at the residual terminal alkene (entry
3).10
Noting the excellent reactivity of 8a-e, we next explored the
RCM reaction of alkynylsilyloxy dienynes that have two terminal
alkenes of similar steric and stereoelectronic character but have
substantially different tether lengths between the ene and the yne
moieties (Scheme 2).
The RCM reactions (0.001 M) of 11a-c showed several salient
features. First, the enyne RCM is uniformly observed over diene
RCM or CM, providing predominantly smaller siloxacycles 12a-c
as a 3:1 to 7.5:1 mixture of trans- and cis-isomers. Second, a larger
difference between the tether lengths of unsymmetrical alkynylsilyl
ethers results in higher selectivity between ring sizes. This trend is
the reflection of a much higher cyclization rate of smaller-sized
rings over that of the larger rings11 in combination with rapid
alkylidene exchange of the larger ring-forming intermediate prior
to its cyclization.12
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10.1021/ja046043n CCC: $27.50 © 2004 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Concentration Effect for Dienyne RCM Selectivity
Figure 1. Concentration-dependent RCM selectivity.
In conclusion, we have developed the alkynylsilyloxy-tethered
dienyne as an effective enyne RCM platform and examined its
metathesis-based ring-closing behavior. High selectivity for smaller
ring sizes was noted from the RCM reaction of dienynes run at
high concentration, providing a new insight into achieving group
selectivity in the enyne RCM process. Further investigation to
elucidate the origin of this increased selectivity at higher concentra-
tion is in progress.
Acknowledgment. We thank WARF, NSF, and the Dreyfus
Foundation for financial support of this work as well as the NSF
and NIH for NMR and mass spectrometry instrumentation. The
general support from CBI traning grant (GM08505) for R.L.M. is
greatly acknowledged.
Supporting Information Available: General procedures and
characterization of represented compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
References
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