Diastereoselective construction of functionalized homoallylic alcohols by Ni-catalyzed diboron-promoted coupling of dienes and aldehydes

Article abstract of DOI:10.1021/ja806113v

The nickel-catalyzed reaction of carbonyls and dienes was accomplished in a regio- and stereoselective fashion employing a stoichiometric amount of bis(pinacolato)diboron. This reductive coupling furnishes an allyl boronic ester as the reaction product, a compound which was readily converted to the derived allylic alcohol by oxidative workup. Copyright

Full text of DOI:10.1021/ja806113v

Published on Web 11/08/2008
Diastereoselective Construction of Functionalized Homoallylic Alcohols by
Ni-Catalyzed Diboron-Promoted Coupling of Dienes and Aldehydes
Hee Yeon Cho and James P. Morken*
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467
Received August 4, 2008; E-mail: morken@bc.edu
Table 1. Ni-Catalyzed Coupling of Dienes, Aldehydes, and B2(pin)2
The dimetalation of unsaturated substrates is an effective tool
for enriching the functional and stereochemical complexity of simple
hydrocarbon substrates.1 In the particular case of diboration, reaction
of alkenes,2 dienes,2b,3 allenes,4 and enones5 provides reactive
intermediates that may participate in stereoselective cascade reaction
sequences. In general, these reactions are energetically highly
favored with the addition of bis(ethyleneglycolato)diboron to
ethylene calculated to be exothermic by 41.7 kcal/mol.6 A useful
extension of this methodology would arise if the reactivity inherent
in diboration reactions could be used to promote multicomponent
coupling processes. Considering the oxophilic nature of boron, an
attractive starting point for these studies is the reductive coupling
of unsaturated hydrocarbons and carbonyls, a transition-metal
catalyzed process that is enabled by the use of metal hydrides,
molecular hydrogen, or their equivalents, to facilitate C-C bond
formation.7 In particular, the coupling of simple dienes and
carbonyls, a Ni-promoted process first discovered by Wilke8 with
subsequent pioneering studies in catalysis by Mori9 and Tamaru,10
was targeted.11 In the context of diboron-promoted coupling, we
considered that this transformation might be a very effective tool
for the preparation of synthetically versatile allylboronates.12
Mechanistic studies by Ogoshi have provided the first structural
evidence that the Ni-promoted reductive (and alkylative) coupling
of dienes and aldehydes is initiated by cyclometalation of the
substrates.13 In the presence of a metal hydride, subsequent σ-bond
metathesis and reductive elimination generate the unsaturated
reaction product (eq 1). Here, we demonstrate that diboron reagents
may participate in a similar σ-bond metathesis reaction, thereby
providing access to organoboronic esters as the reaction product
(eq 2). A notable aspect of this reaction is that the products are
obtained with excellent levels of stereoselectivity and with regi-
oselectivity that complements the stepwise diene diboration/carbonyl
allylation reaction.12b A unique and particularly useful feature of
this process is that oxidative workup directly provides a functionally
and stereochemically enriched product whose synthesis would
otherwise require multiple steps.
a Determined by analysis of unpurified reaction. b Isolated yield of
purified material. c Run using 10 mol % Ni(cod)2, 10 mol % PCy3, and
a reaction time of 14 h. d Run using 10 mol % Ni(cod)2, 10 mol %
P(OEt)3. With PCy3 this reaction provides 10% yield. Purification was
aided by acetylation.
Initial experiments surveyed the Ni-catalyzed, room temperature
reaction of bis(pinacolato)diboron, trans-1,3-pentadiene, and ben-
zaldehyde. After extensive optimization of reaction parameters
(ligand, solvent, temperature, concentration), the optimal set of
reaction conditions was found to include PCy3 as the ligand, THF
as the solvent, at room temperature, and a substrate concentration
of 0.2 M. With these conditions, benzaldehyde, trans-1,3-pentadi-
ene, and B2(pin)2 were effectively coupled and, after oxidative
workup, the allylic alcohol product was obtained in good yield and
stereoselectivity (Table 1, entry 1).
A number of other aldehydes and dienes participate in the
stereoselective diboron-promoted diene-aldehyde coupling. As
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16140 J. AM. CHEM. SOC. 2008, 130, 16140–16141
10.1021/ja806113v CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
depicted in Table 1, aromatic aldehydes tend to be effective
substrates with B2(pin)2 and trans-piperylene (Table 1, entries 1-5).
With the more encumbered 3-methylpentadiene (entries 6, 7) a
versatile trisubstituted alkene was furnished; within the limits of
detection, this product was obtained as a single stereoisomer with
respect to the stereocenters and the alkene. With butadiene (entry
8) reaction yields suffered, even with further optimization of
reaction conditions. In contrast to butadiene, isoprene (entry 9)
reacted with comparable efficiency as compared to 1,3-pentadiene
Supporting Information Available: Characterization and proce-
dures. This material is available free of charge via the Internet at http://
pubs.acs.org.
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NMR analysis of the oxidation product. With this substrate, the
use of P(OEt)3 as the ligand was criticalswith PCy3, significant
amounts of a double allylation product, incorporating 2 equiv of
the aldehyde, were obtained. Entries 10 and 11 document that the
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In conclusion, we have demonstrated that diboron reagents can
be used to facilitate stereoselective intermolecular coupling of dienes
and aldehydes. The reaction products are particularly well suited
for the construction of polyketide natural products and other useful
chiral materials. Studies in asymmetric catalysis and in alternate
transformations of the allyl boron product are underway.
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Acknowledgment. Support by the NIGMS (Grant GM-59417)
and Merck is gratefully acknowledged, as is the NSF for support
of the BC Mass Spectrometry Center (Grant DBI-0619576).
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