Dehydrogenative cyclocondensation of aldehydes, alkynes, and dialkylsilanes

Article abstract of DOI:10.1021/ja803774s

The nickel-catalyzed coupling of aldehydes, alkynes, and dialkylsilanes results in an unusual dehydrogenative cyclocondensation process to afford five-membered silacyclic products. The process allows dialkylsilanes to serve as a silylene synthetic equivalent. A mechanistic pathway for the process involving the formation of an aldehyde/alkyne-derived nickel metallacycle followed by sequential σ-bond metathesis processes involving the two Si-H bonds has been proposed. Copyright

Full text of DOI:10.1021/ja803774s

Published on Web 07/04/2008
Dehydrogenative Cyclocondensation of Aldehydes, Alkynes, and
Dialkylsilanes
Ryan D. Baxter and John Montgomery*
Department of Chemistry, UniVersity of Michigan, 930 North UniVersity AVenue, Ann Arbor, Michigan 48109-1055
Received May 20, 2008; E-mail: jmontg@umich.edu
Table 1. Dehydrogenative Cyclocondensationsa
Oxasilacyclopentenes and oxasilacyclopentanes are useful synthetic
intermediates in a broad variety of organic transformations including
oxidations, cross-couplings, and cycloadditions.1 They are typically
prepared by either intramolecular hydrosilylations2 or silylformyla-
tions,3 ring-closing metathesis reactions,4 or cycloadditions of silylene
synthetic equivalents.1a,5 The latter of these strategies has the advantage
of utilizing two simple π-components in a multicomponent cycload-
dition that involves silylene transfer from a silylene synthetic equiva-
lent. While impressive advances have been made in a number of
reactions involving a variety of silylene synthetic equivalents, the use
of silacyclopropanes has emerged as the most general protocol.5a–c
However, the impressive scope of reactions and utility of the five-
membered silacyclic products is somewhat offset by the requirement
for prior synthesis and bulb-to-bulb distillation of the silacyclopropane
starting material.
The dehydrogenative cyclocondensation of dialkylsilanes with two
π-components would provide an attractive strategy for preparation of
silacyclic compounds while having the advantage of employing a
simple, stable, commercially available silylene synthetic equivalent.
Whereas fundamental advances have been made in the dehydrogena-
tion of dialkylsilanes with transition metals to generate metal silylene
a Reaction conditions: Ni(COD)2, IMes ·HCl, KO-t-Bu (10 mol %
each), Al(O-i-Pr)3 (1.5 equiv), aldehyde (1.0 equiv), alkyne and Et2SiH2
(1.1 equiv each), THF/toluene, rt. Isolated chemical yield and
regioselectivity of alkyne insertion are provided in parentheses.
complexes,6 the catalytic incorporation of the silylene unit derived from
a dialkylsilane into an organic product has not been demonstrated.7
Herein we describe an unexpected catalytic process that establishes
the viability of dehydrogenative cyclocondensations of dialkylsilanes,
and that provides a novel entry to oxasilacyclopentenes in a one-step
process from commercial reagents.
In the course of studying nickel-catalyzed reductive coupling
reactions of aldehydes, alkynes, and dialkylsilanes,8 we found, in
some instances, that the expected silylated allylic alcohol 1 was
accompanied by the unexpected formation of silacycle 2 in addition
to other minor products derived from hydrosilylation of the aldehyde
and/or alkyne (eq 1). Compound 1 was not converted to 2 under
Couplings of benzaldehyde with phenyl propyne and with 3-hexyne
proceeded with moderate efficiency (products 2a and 2b), and
cyclohexyl carboxylaldehyde and butyraldehyde were also excellent
participants with various alkynes (products 2c-2f). Whereas
couplings with phenyl propyne were uniformly highly regioselective
(products 2a, 2c, and 2d), a coupling with 2-octyne proceeded with
poor selectivity (product 2f). Additionally, couplings of a terminal
alkyne (product 2g), a conjugated enyne (product 2h), and an
R-silyloxy aldehyde (product 2i) were efficient, with each of these
examples proceeding with excellent regiocontrol of the alkyne
insertion.
Although the net dehydrogenative cyclocondensation exhibits some
similarity to the copper-catalyzed addition of silacyclopropenes to
aldehydes, as reported by Woerpel,5a the scope and regioselectivity
of the two procedures are markedly different. For example, couplings
of butyraldehyde and phenyl propyne are highly regioselective in both
procedures. Notably, the nickel-catalyzed procedure affords compound
2d (Table 1), whereas the copper-catalyzed silacyclopropene procedure
produces the opposite regioisomer with >95:5 selectivity. In addition
to this regioselectivity comparison, several lines of reasoning suggest
that the nickel-catalyzed process proceeds by a different mechanism
than that operative in true silylene transfer reactions. First, the
silacyclopropenes used in silylene addition reactions by Woerpel are
unreactive with aldehydes upon exposure to the nickel catalyst and
Lewis acid employed in the coupling procedure developed herein.
Additionally, omitting the aldehyde component in the nickel-catalyzed
the conditions of catalysis. The dehydrogenative three-component
entry to compound 2 was of particular interest to us considering
the potential impact of developing dialkylsilanes as silylene
synthetic equivalents in multicomponent cycloadditions. Extensive
variation of ligand structure, stoichiometry, order of addition, Lewis
acidic additives, and silane structure illustrated that near-optimal
yields for production of compound 2 could be achieved with the
aldehyde as the limiting reagent and only a slight excess of the
alkyne and silane (1.1 equiv each, added by syringe drive). Al(O-
i-Pr)3 and Et2SiH2 were the optimum Lewis acid and silane
components of those examined. Using these optimized conditions,
the scope and generality of the dehydrogenative cyclocondensation
of aldehydes, alkynes, and Et2SiH2 was explored (Table 1).
9
9662 J. AM. CHEM. SOC. 2008, 130, 9662–9663
10.1021/ja803774s CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Regioselectivity of Aldehyde, Alkyne, Silane Couplings
Given the potential of mechanistic similarities in the production of
compounds 2 and 3, chiral ligand 7, which was recently developed
for use in asymmetric couplings of aldehydes, alkynes, and
trialkylsilanes,9d was examined in the asymmetric preparation of 2c.
This preliminary experiment proceeded in 56% ee and 55% isolated
yield, which represents the first asymmetric cycloaddition involving
formal silylene transfer (eq 2).
entry
silane
ligand
products (ratio)
% yield
1
2
3
4
Et2SiH2
Et3SiH
Et2SiH2
Et3SiH
IMes
IMes
IPr
2f:2j (62:38)
3a:3b (63:37)
2f:2j (12:88)
3a:3b (10:90)
65
76
38
58
In summary, the use of a dialkylsilane as a silylene synthetic
equivalent in a catalytic multicomponent cyclocondensation has been
demonstrated for the first time. Synthetically useful silacycles are
prepared by the procedure, and a mechanism involving nickel
metallacycles derived from oxidative cyclization of Ni(0) with an
aldehyde and alkyne is proposed. Additionally, the first example of
the asymmetric formation of a silacyclic product via three-component
cycloaddition is provided. Further elaboration of this conceptual
framework in other classes of reactions is in progress.
IPr
Scheme 1. Proposed Mechanism
Acknowledgment. The authors wish to acknowledge receipt of
NSF grant CHE-0718250 in support of this work. R.D.B. acknowl-
edges receipt of a U.S. DOE GAANN Fellowship (P200A060119).
Scott Bader is thanked for helpful suggestions.
Supporting Information Available: Full experimental details and
copies of NMR spectral data (PDF). This material is available free of charge
via the Internet at http://pubs.acs.org.
process involving dialkylsilanes leads to simple hydrosilylation of the
alkyne, with no evidence for formation of silylene-derived products
being obtained. Finally, aldehyde/alkyne/dialkylsilane oxidative cy-
cloadditions proceed with essentially identical regioselectivity as
aldehyde/alkyne/trialkylsilane couplings9 across a range of ligand
structures. These very close parallels suggest involvement of a common
intermediate in these two nickel-catalyzed reactions, and the latter of
these pathways involving trialkylsilanes cannot involve a silylene
species. To illustrate this issue, the regioselectivity of the nickel-
catalyzed couplings of cyclohexyl carboxaldehyde and 2-octyne with
diethylsilane and triethylsilane, using both IMes and IPr as ligand, was
examined. The solvent composition, Lewis acid concentration, and all
other variables were identical in these comparative experiments. In
couplings involving the IMes/Ni(0) catalyst system, couplings with
diethylsilane proceeded with 62:38 regioselectivity (Table 2, entry 1),
whereas couplings with triethylsilane proceeded with 63:37 regiose-
lectivity (Table 2, entry 2). Similarly, couplings with the IPr/Ni(0)
catalyst system proceeded with the reversed regioselectivity both in
couplings of diethylsilane (12:88 ratio, Table 2, entry 3) and tri-
ethylsilane (10:90 ratio, Table 2, entry 4).
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J. AM. CHEM. SOC. VOL. 130, NO. 30, 2008 9663