Simple alkenes as substitutes for organometallic reagents: Nickel-catalyzed, intermolecular coupling of aldehydes, silyl triflates, and alpha olefins

Article abstract of DOI:10.1021/ja055363j

A nickel-catalyzed method for the three-component coupling of alkenes (ethylene and alpha olefins), aldehydes, and silyl triflates is described, and this process represents the first catalytic method for coupling aldehydes and alkenes to give allylic alco

Full text of DOI:10.1021/ja055363j

Published on Web 09/17/2005
Simple Alkenes as Substitutes for Organometallic Reagents:
Nickel-Catalyzed, Intermolecular Coupling of Aldehydes, Silyl Triflates, and
Alpha Olefins
Sze-Sze Ng and Timothy F. Jamison*
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
Received August 5, 2005; E-mail: tfj@mit.edu
Table 1. Nickel-Catalyzed, Three-Component Coupling of
Alkenes, Aldehydes, and Silyl Triflates
Aliphatic terminal alkenes (alpha olefins) are produced in metric
megaton amounts each year, and these chemical feedstocks are
starting materials for the preparation of many classes of organic
compounds.1 The value-added component of catalytic intermolecular
reactions of these alkenes, such as Ziegler-Natta oligomerization,2
the Heck reaction,3 and cross-metathesis,4 is especially high because
they convert an inexpensive raw material into a more highly
functionalized compound or polymer with concomitant formation
of one or more carbon-carbon bonds. Whereas catalytic carbonyl-
ene reactions between alpha olefins and aldehydes provide ho-
moallylic alcohols,5 there is no method for joining these two
building blocks to provide allylic alcohols.6 Herein we report that,
in the presence of a nickel catalyst and a silyl triflate, ethylene and
alpha olefins can be coupled with aldehydes to form allylic alcohol
derivatives (eq 1).
a
Several research groups, including our own, have developed
metal-catalyzed, intermolecular reductive coupling reactions of
aldehydes with alkynes,7 1,3-dienes,8 allenes,9 enoate esters,10
enones,11 and enals.12 In all of these, an electron-deficient π-bond,
in conjunction with a reducing agent, functions as an anion
equivalent. On the other hand, catalytic intermolecular coupling
(reductive or otherwise) of alpha olefins and aldehydes has not been
reported.13,14 Nickel-promoted, intramolecular alkene-aldehyde
reductive coupling was recently described, but this process required
a stoichiometric amount of nickel and was not effective in
intermolecular cases.15,16
We have found that nickel catalysis of intermolecular alkene-
aldehyde coupling is possible when certain phosphine ligands, a
silyl triflate, and an amine base are employed. As shown in eq 1
and Table 1, ethylene, aromatic aldehydes, and silyl triflates undergo
nickel-catalyzed coupling under very mild conditions (1 atm
H2CdCH2, room temperature), yielding a three-component cou-
pling17 product, a silyl ether of an allylic alcohol (entries 1-7). In
some cases, the isolated yield of the product is greater than 90%
(entries 3-5), highlighting the efficiency and ease of this method
of assembling protected allylic alcohols in a single operation. In
general, triethylsilyl triflate is the superior silyl triflate under these
conditions, but trimethylsilyl and tert-butyldimethylsilyl triflate also
provide some flexibility in which protective group appears in the
product (entries 6 and 7).
a See eq 1. Standard conditions (entries 1-9): To a solution of Ni(cod)2
(20 mol %) and tris(ortho-methoxyphenyl)phosphine (40 mol %) in toluene
at 23 °C under ethylene (balloon, 1 atm) were added triethylamine (600
mol %), the silyl triflate (175 mol %), and the aldehyde (100 mol %). The
mixture was stirred 2-8 h at room temperature, and purification by
chromatography (SiO2) afforded products 1a-i. For entries 10-12, dicy-
clohexylphenylphosphine and the alkene shown were used in place of
tris(ortho-methoxyphenyl)phosphine and ethylene, respectively (reaction
under Ar). See Supporting Information. b A silyl ether of a homoallylic
alcohol was also isolated in 10-20% yield. See Supporting Information.
8). Entry 9 demonstrates another feature of this reaction, functional
group compatibility with esters. A competing (yet unsurprising)
side reaction occurs in coupling reactions with aliphatic aldehydes
bearing at least one hydrogen adjacent to the carbonyl, enol silane
formation.18
Monosubstituted olefins also undergo coupling with aldehydes
in the presence of a similar reagent/catalyst combination (entries
10-12). An alpha olefin is thus a functional equivalent of a
2-alkenylmetal reagent, complementary to a 1-alkenylmetal reagent
Notably, this transformation is very tolerant of sterically demand-
ing aliphatic aldehydes (entries 8 and 9). Pivaldehyde, ethylene,
and Et3SiOTf undergo smooth coupling to provide the triethylsilyl
ether of tert-butyl vinyl carbinol in one step and in good yield (entry
9
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C O M M U N I C A T I O N S
in addition reactions to aldehydes. As entry 12 demonstrates, this
transformation tolerates more highly substituted alkenes.19
The chief byproduct in these reactions is the isomeric homoallylic
alcohol derivative (2j in Figure 1).20 Remarkably, only one (1j) of
the three possible allylic alcohol derivatives (1j, 3, and 4) is formed
in greater than 1% yield in all such reactions investigated to date
(Figure 1).
Acknowledgment. Support for this work was provided by the
National Institute of General Medical Sciences (GM-063755). We
also thank the NIGMS (GM-072566), NSF (CAREER CHE-
0134704), Amgen, Boehringer Ingelheim, Bristol Myers-Squibb,
GlaxoSmithKline, Johnson & Johnson, Merck Research Labora-
tories, Pfizer, the Sloan Foundation, Wyeth, and the Deshpande
Center (MIT) for generous financial support. We are grateful to
Dr. Li Li for obtaining mass spectrometric data for all compounds
(MIT Department of Chemistry Instrumentation Facility, which is
supported in part by the NSF (CHE-9809061 and DBI-9729592)
and the NIH (1S10RR13886-01)).
Figure 1. Major and minor products.
Supporting Information Available: Experimental procedures and
data for all new compounds (PDF). This material is available free of
charge via the Internet at http://pubs.acs.org.
Our explanation for this product distribution and the other
observations noted above is summarized in Scheme 1. One of the
key intermediates might be oxametallacycle A,15-16 which would
lead to the observed allylic product (1j) by reaction with the silyl
triflate, cleavage of the Ni-O bond, and then â-H elimination. Even
though it would represent an alternative means by which 1j could
be formed, â-H elimination directly from A is unlikely since the
transition state required would be highly strained. This notion is
supported by the fact that allylic alcohol products 3 and 4 are
generally not formed in the reaction; they would result from the
corresponding â-H elimination from regioisomer B.
References
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(4) Handbook of Metathesis; Grubbs, R. H., Ed.; John Wiley & Sons: New
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Scheme 1. Mechanistic Hypothesis for Product Distribution
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highly electron-deficient alkenes, such as conjugated enoate esters.
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The homoallylic alcohol byproduct is most easily explained by
oxametallacycle regioisomer B. With the alkyl chain of the olefin
adjacent to the Ni center, the transition state for â-H elimination
directly from B may be less strained than those from A and B that
would lead to allylic alcohol products (see above). Another
possibility is that, as in the case of A, B first reacts with the silyl
triflate. Subsequent â-H elimination toward the newly installed
carbinol center, which would lead to the generally unobserved allylic
alcohol derivatives 3 and 4, might thus be disfavored for steric
and/or electronic reasons.
Scheme 2. Alkenes as Substitutes for Organometallic Reagents
(14) Nickel-catalyzed, asymmetric hydrovinylation of vinylarenes (coupling
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(16) While this paper was under review, two examples of intramolecular, nickel-
catalyzed alkene-ketone coupling were reported: Ogoshi, S.; Ueta, M.;
Arai, T.; Kurosawa, H. J. Am. Chem. Soc. 2005, 127, ASAP, DOI:
10.1021/ja0542486.
Conceptually, as depicted in Scheme 2, the alkene in a carbonyl-
ene reaction serves as a replacement for an allylmetal reagent, and
conversely, in the nickel-catalyzed reaction presented here, an
alkene functions as an alkenylmetal reagent. Compared to the
corresponding organometallic reagent, the alkene in this unprec-
edented bond construction has important advantages, including
greater off-the-shelf availability and greater functional group
compatibility. The development of an enantioselective version of
this process and its use as a fragment coupling reaction in complex
molecule synthesis are both underway.
(17) Recent reviews: (a) Multicomponent Reactions; Zhu, J., Bienayme´, H.,
Eds.; Wiley-VCH: Weinheim, Germany, 2005. (b) Ramo´n, D. J.; Yus,
M. Angew. Chem., Int. Ed. 2005, 44, 1602-1634.
(18) For example, in the case of cyclohexanecarboxaldehyde, the product ratio
is about 2:1, favoring the silyl ether.
(19) Di- and tetrasubstituted alkenes also do not react under these conditions.
(20) When tris(o-methoxyphenyl)phosphine was employed, the homoallylic
product was isolated in greater than 75% yield.
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