Catalytic enantioselective allylation of dienals through the intermediacy of unsaturated π-allyl complexes

Article abstract of DOI:10.1021/ja9058537

(Chemical Equation Presented) The nickel-catalyzed enantioselective addition of allylboronic acid pinacol ester [allylB(pin)] to >,β,γ,δ-unsaturated aldehydes is described. This reaction results in a remarkable inversion of substrate olefin geometry, providing the Z,E-configured reaction product in good enantioselectivity and olefin stereoselectivity. The reaction appears to proceed by conversion of the dienal to an unsaturated B-allyl complex followed by reductive elimination via transition state II. Enantioselectivities range from 73-94% ee for a range of δ-substituted dienals when chiral ligand L3 is employed.

Full text of DOI:10.1021/ja9058537

Published on Web 08/13/2009
Catalytic Enantioselective Allylation of Dienals through the Intermediacy of
Unsaturated π-Allyl Complexes
Ping Zhang and James P. Morken*
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467
Received July 14, 2009; E-mail: morken@bc.edu
Scheme 2
3,3′-Reductive elimination of bis(allyl)metal species results in C-C
bond-forming allyl coupling at a site remote from the metal center.
This mechanistic postulate was recently described computationally by
Echavarren1 and can be used to understand an array of reactions from
Yamamoto’s allylative dearomatization reaction2 to the Tsuji allyla-
tion.3 Recently, we reported that Ni and Pd complexes can catalyze
the enantioselective conjugate addition of allylboronic acid pinacol ester
[allylB(pin), 2 in Scheme 1] to dialkylidene ketones (1 in Scheme 1).4
Mechanistic studies suggest that this conjugate addition also proceeds
absence of catalyst), and like reactions through I that deliver the E
by 3,3′-reductive elimination, albeit in this case from unsaturated π-allyl
complex I. Structure I is obtained by boron Lewis acid-promoted
electron transfer from either Ni(0) or Pd(0) to the enone followed by
transmetalation of the allyl group from boron to the transition metal.5
Notably, simple enones and their derivatives are inert under the reaction
conditions, a feature which is attributed to the reaction mechanism.
enolate,4 reaction through II furnishes the Z alkene.
Previous investigations of the catalytic enantioselective conjugate
allylation reaction employed taddol-derived phosphonite L1 for optimal
selectivity.7 As depicted in Table 1, this ligand structure is effective
for the asymmetric 1,2-allylation of aldehyde 4, but the enantioselec-
tivity is minimal (entry 1). Analysis of related ligand structures revealed
that phosphonites are generally superior to phosphoramidites and that
phosphonite L3 is optimal: in THF at room temperature, a 71% yield
of alcohol (E,Z)-5 was obtained with an enantiomeric purity of 75%
ee. Notably, the reaction with ligand L3 occurs rapidly at room
temperature, with complete conVersion achieVed in 25 min! The high
rate of this reaction suggested that it might occur efficiently even at
lower temperature. Indeed, at -35 °C, the catalytic reaction still
occurred, and while 18 h was required to achieve complete conversion,
the enantioselectivity and olefin stereoselectivity were enhanced
significantly (Table 2).
Scheme 1
Under optimized conditions, many δ-substituted dienals also
participate in the Ni-catalyzed enantioselective allylboration reaction.
Table 1. Ni-Catalyzed Enantioselective Dienal Allylation
Considering the utility of the allyl unit in organic synthesis, we have
begun to investigate whether 3,3′-reductive elimination might enable
new types of allylation reactions.6 In light of the structural requirements
of transition state I in Scheme 1, we considered it plausible that
R,ꢀ,γ,δ-unsaturated aldehydes (3) might access intermediates such as
II or III, thereby gaining access to a path for low-barrier 3,3′-reductive
elimination. In this report, we describe the first examples of this
allylation, a process that delivers the 1,2-addition product and results
in a remarkable inversion of substrate olefin geometry. Significantly,
with appropriate chiral ligands, reactions of substrate class 3 can occur
with high enantioselectivity and provide products that are not readily
accessed by other catalytic allylation reactions.
To investigate the rapidity with which catalysis of the dienal
allylation might proceed, the reaction between sorbic aldehyde (4) and
allylB(pin) was examined (Scheme 2). These reactants undergo
noncatalyzed reaction at room temperature in THF solvent, achieving
>95% conversion to (E,E)-5 after 15 h ([substrate]0 ) 0.5 M).
Remarkably, in the presence of Ni(cod)2 and PCy3, the reaction is
complete in 40 min, and (E,Z)-5 rather than the 1,2 addition product
(E,E)-5 is the predominant reaction product. Consistent with the
discussion above, the rate acceleration appears to be restricted to dienals
(crotonaldehyde reacts with comparable rates in both the presence and
a Isolated yield of purified material. b Determined by NMR analysis
of the unpurified product. c Determined by chiral GC analysis.
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12550 J. AM. CHEM. SOC. 2009, 131, 12550–12551
10.1021/ja9058537 CCC: $40.75  2009 American Chemical Society

C O M M U N I C A T I O N S
Scheme 3
As shown in Table 2, the stereoselectivity is dependent upon the diene
substituents even when these groups are five atoms away from the
newly formed stereocenter. This observation is completely consistent
with the proposed reaction mechanism. Notably, the reaction delivers
the E,Z stereoisomer as the predominant product. The E,E olefin
isomer, when observed, is racemic and assumed to arise from
noncatalyzed reaction that occurs during room-temperature workup.
Indeed, addition of 30 equiv of acetaldehyde prior to workup served
to eliminate much of the E,E product. In regard to the substrate scope,
aromatic and aliphatic substituents are tolerated at the δ carbon and
provide products with high enantiomeric purity. In view of the lability
of allylic oxygenated substituents in the presence of late-transition-
metal catalysts, it is notable that the substrates in entries 6 and 7 provide
good product yields and high levels of stereocontrol.
In conclusion, we have described a unique catalytic enantioselective
allylation of unsaturated carbonyls that appears to occur by 3,3′-
reductive elimination. The functional group pattern that is packaged
in the reaction products is relatively unique and should be amenable
to rapid complexity generation. Future studies regarding the scope of
this transformation and its use in asymmetric synthesis are in progress.
Table 2. Scope of Ni-Catalyzed Enantioselective Dienal Allylationa
Acknowledgment. Frontier Scientific is thanked for a donation
of allylB(pin), as are the NIGMS (R01 GM-64451) and the NSF (DBI-
0619576; BC Mass Spectrometry Center).
Supporting Information Available: Characterization and procedures.
This material is available free of charge via the Internet at http://
pubs.acs.org.
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a For entries 1, 3, and 5-10, the reaction was carried out in a
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