Ni-catalyzed borylative Diene-Aldehyde coupling: The remarkable effect of P(SiMe3)3

Article abstract of DOI:10.1021/ja101513d

The nickel-catalyzed reaction of carbonyls and dienes was accomplished in a regio- and stereoselective fashion employing a stoichiometric amount of bis(pinacolato)diboron. In the presence of P(SiMe₃)₃, this reductive coupling furnishes allyl boronic esters which are regioisomeric to those obtained with PCy₃ as the ligand. The coupling product may be subject to oxidation, which furnishes the derived 1,3-diol, or allylation with an additional aldehyde, which furnishes the derived 1,6-diol in a stereoselective fashion.

Full text of DOI:10.1021/ja101513d

Published on Web 05/18/2010
Ni-Catalyzed Borylative Diene-Aldehyde Coupling: The Remarkable Effect of
P(SiMe3)3
Hee Yeon Cho and James P. Morken*
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467
Received February 25, 2010; E-mail: morken@bc.edu
Scheme 1
Rapid construction of complex molecules with high regio- and
stereoselectivity is a central objective in organic synthesis. In this
regard, reactions that result in the formation of multiple new bonds
and that establish multiple stereocenters are particularly valuable.1
To address this topic, we recently initiated studies on the borylative
coupling of unsaturated substrates.2 In one manifestation of this
strategy, we examined the Mori-Tamaru Ni-catalyzed coupling
of aldehydes and dienes3,4 but employed bis(pinacolato)diboron
(B2(pin)2) as the reducing agent. In the presence of PCy3 as an
ancillary ligand for nickel, reaction product 3 (Scheme 1) is
furnished as a single constitutional and stereoisomer. In accord with
mechanistic studies by Ogoshi,5 it is likely that this reaction oc-
curs by a pathway involving oxidative cyclometalation to give 1;
subsequent transmetalation would furnish 2 and reductive elimina-
tion to connect C1 with the boryl ligand would release 3 from the
catalyst. We considered that other ligands might alter the regiose-
lectivity of the reductive elimination by connection of C3 and the
boryl group and, thereby, furnish allylboronate 4 as the reaction
product. The structural features of compound 4 s three contiguous
stereocenters, an R-chiral allylboronate,6 and a functional group
pattern that maps onto polyketides s made this a compelling
inquiry. In this report, we describe a remarkable turnover in
regioselectivity of the borylative diene/aldehyde coupling when
PCy3 is replaced with P(SiMe3)3.
Table 1. Effect of Ligand On the Ni-Catalyzed Diborylative Coupling
entry
ligand
5:6
% yielda
d.r.b
1
2
3
4
5
6
7
8
9
none
PCy3
>20:1
>20:1
>20:1
>20:1
>20:1
>20:1
1:2
39
69
71
63
16
40
34
55
45
1:1
>20:1
6:1
5:1
>20:1
4:1
2:1
4:1
>20:1
P(t-Bu)3
PPh3
P(NMe2)3
P(OEt)3
PEt3
PMe3
P(SiMe3)3
1:3
1:12
a Isolated yield of major product. b d.r. of major product.
Initial exploratory studies focused on the nickel catalyzed reaction
between 1 equiv each of 1,3-pentadiene, benzaldehyde, and B2(pin)2.
While PCy3 and P(t-Bu)3 both promoted formation of terminal boronate
3 (analysis after oxidative workup with hydrogen peroxide), other alkyl
and aryl phosphines, triaminophosphines, and simple phosphites were
either ineffective or resulted in poor selectivity (Table 1). HoweVer,
when commercially aVailable P(SiMe3)3 was employed, compound 4
was obserVed with excellent selectiVity.
In addition to compound 4, byproducts comprising two aldehydes
and one diene or two dienes and one aldehyde were also observed.
Reasoning that reaction of 4 with unreacted aldehyde might compete
with the catalytic process at later stages of reaction and deliver
some of these byproducts, the concentrations of B2(pin)2 and
pentadiene were increased. This strategy furnished optimal condi-
tions for this three-component process. As depicted in Table 2, upon
oxidation the borylative coupling reaction converts benzaldehyde
and 1,3-pentadiene to the derived 1,3-diol with >20:1 diastereose-
lectivity.7 Examination of other substrates revealed that, in general,
the reaction is effective for aromatic and heteroaromatic aldehydes
and generally delivers the 1,3-diol with excellent regio- and
stereocontrol. To determine whether this transformation might apply
to more common synthetic building blocks, the aliphatic aldehydes
in entries 8-12 were also studied. These experiments suggest that
the reaction can be effective with both linear and branched aliphatic
aldehydes; additionally, a simple R-chiral aldehyde was found to
react with Felkin selectivity thereby opening the possibility for
asymmetric synthesis (entry 12).
As alluded to in the introduction, general structure 4 possesses
an R-chiral allylic boronate, a motif that often engages in highly
selective carbonyl allylation reactions. To probe the capacity for
structures such as 4 to participate in stereoselective allylations,
benzaldehyde and 1,3-pentadiene were subjected to borylative
coupling and, after 12 h, isobutyraldehyde was added to the reaction
mixture. This single-pot reaction sequence delivered 1,6-diol 9
(Scheme 2) in good yield, as a single regioisomer, and with
excellent levels of 1,5-stereoinduction (>20:1 d.r.) and olefin
stereocontrol. Considering the olefin configuration in the reaction
product, it appears plausible that boronate 7 reacts with isobutyral-
dehyde by way of transition structure 8 with the R-substituent
occupying a pseudoequatorial position.8
P(SiMe3)3 is a relatively unknown ligand in transition metal
catalysis,9 and the reversal in regioselectivity when it is used in place
of PCy3 or P(t-Bu)3 deserves comment. Data in Table 1 reveal that
smaller ligands may favor formation of 4 (entries 7 and 8 versus entries
2 and 3), which might suggest that P(SiMe3)3 simply serves as a
precursor to PH3 (reaction with adventitious moisture).10 However, in
situ 31P NMR analysis of reactions in the presence of P(SiMe3)3 shows
that most of the ligand remains unmodified (31P δ ) -251.4 ppm)
over the course of the catalytic reaction.11 The fact that the cone angle
of P(SiMe3)3 is similar to that of P(t-Bu)3 (178° versus 182°)12 suggests
that the difference in regioselectivity observed with these ligands may
arise from electronic rather than steric differences. While the 13C NMR
9
7576 J. AM. CHEM. SOC. 2010, 132, 7576–7577
10.1021/ja101513d  2010 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Ni(cod)2/P(SiMe3)3-Catalyzed Diborylative Coupling
indicate that P(SiMe3)3 can act as an electron acceptor. Thus a tentative
hypothesis is that the large cone angle of P(SiMe3)3, combined with
an ability to act as an electron acceptor, may facilitate reductive
elimination of 4 from 2, prior to allyl isomerization required for
formation of 3.16
Acknowledgment. This work was supported by the NIGMS
(GM-59417) and the NSF (BC Mass Spec Center; Grant No. DBI-
0619576). We thank AllyChem Co., Ltd. for B2(pin)2. H.Y.C. is
grateful for a Rodin Fellowship.
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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a Determined by 1H NMR analysis of unpurified reaction mixture.
b Isolated yield of purified material. Value is an average of two
experiments. c Run with 1.1 equiv of diene and 1.2 equiv of B2(pin)2.
d Ratio refers to Felkin/anti Felkin selectivity. Reaction for 24 h.
Scheme 2
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(16) Consistent with this hypothesis, the borylative coupling reaction with
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electronically similar ligands, analyses by both Bartik14 and Helm15
JA101513D
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J. AM. CHEM. SOC. VOL. 132, NO. 22, 2010 7577