Ni0-catalyzed regio- and stereoselective coupling reaction of Me3B, isoprene, and aldehydes

Article abstract of DOI:10.1016/S0040-4039(00)01079-0

In the presence of Ni(acac)₂ (0.1 equiv.), the three components of trimethylborane, isoprene, find aromatic and aliphatic aldehydes' combine to produce 1-substituted 3-methyl-3-hexenols (3) in good yield and with high regio- and stereoselectivity (E:Z > 13:1). (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01079-0

Tetrahedron Letters 41 (2000) 6789±6793
Ni0-catalyzed regio- and stereoselective coupling
reaction of Me3B, isoprene, and aldehydes
Masanari Kimura, Kazufumi Shibata, Yoshinobu Koudahashi
and Yoshinao Tamaru*
Department of Applied Chemistry, Faculty of Engineering, Nagasaki University, 1-14 Bunkyo-Machi,
Nagasaki 852-8521, Japan
Received 26 April 2000; revised 12 June 2000; accepted 23 June 2000
Abstract
In the presence of Ni(acac)2 (0.1 equiv.), the three components of trimethylborane, isoprene, and
aromatic and aliphatic aldehydes combine to produce 1-substituted 3-methyl-3-hexenols (3) in good yield
and with high regio- and stereoselectivity (E:Z>13:1). # 2000 Elsevier Science Ltd. All rights reserved.
Keywords: aldehydes; boron and compounds; dienes; nickel and compounds.
Transition metal-catalyzed processes that allow the coupling of two di€erent components at
the 1,2- or 1,4-positions of 1,3-dienes in one pot are particularly useful in the synthesis of highly
functionalized molecules, especially when they utilize simple, readily available starting materials
and provide products with high regio- and stereoselectivity.1
ꢀ1†
ꢀ2†
* Corresponding author. Fax: +81 95 847 9008; e-mail: tamaru@net.nagaski-u.ac.jp
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01079-0

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Recently, we have demonstrated that, in the presence of a catalytic amount of Ni(acac)2
(acac=acetylacetonate), 1,3-butadiene reacts at the C1 and C4 positions with Me2Zn and
benzaldehyde to provide (E)-1-phenyl-3-hexenol (2) in good yield and with excellent stereo-
selectivity (Eq. (1)).2 Isoprene undergoes a similar three-component connection reaction,
combining regioselectively with benzaldehyde at the C1 position and with Me2Zn at the C4
position (Eq. (2)). The yield is quite satisfactory. Unfortunately, however, the stereoselectivity is
rather poor, and a mixture of (E)- and (Z)-1-phenyl-3-methyl-3-hexenols (3a) is produced in a
ratio of 2.2:1.
Here we would like to disclose that Me3B is able to take the place of Me2Zn for the above
mentioned nickel-catalyzed three-component connection reaction and a€ords 2 and 3a in
reasonable yield (Eq. (1) and Eq. (2)). Especially rewarding here is the excellent stereoselectivity
that is attained in the reaction with isoprene; a mixture of (E)- and (Z)-3a was produced in a ratio of
as high as 20:1. Furthermore, to the best of our knowledge, this is the ®rst example demonstrating
that the methyl group of trimethylborane is capable of being accommodated in the products 2
and 3a, most likely through intermediary transmetallation of the methyl group from B to Ni2+ of
p-allylnickel intermediates (vide infra).
From a practical point of view, there seemed to be no advantages to using Me3B in place of
Me2Zn for the reaction with butadiene; Me2Zn exclusively provides (E)-2 in much better yield
than Me3B (Eq. (1)). Accordingly, we focused our attention on the reaction of Me3B with
isoprene toward aldehydes. Trimethylborane (4 mmol) was generated by adding either MeLi (12
mmol, ether solution) or MeMgBr (12 mmol, ether solution) into BCl3 (4 mmol, n-heptane
solution) at 0ꢁC. After stirring for 2 h at 0ꢁC, the Me3B solution was transferred into a THF (10
ml) solution of isoprene (8 mmol), benzaldehyde (2 mmol), and Ni(acac)2 (0.2 mmol) through a
cannula, and this mixture was stirred under N2 for several hours at room temperature. After
usual extractive workup (ethyl acetate) and puri®cation by ¯ash column chromatography over
silica gel (hexane:ethyl acetate 64:1, v/v), 3a was isolated.3 Results for the reactions with Me3B
generated from MeLi and with that generated from MeMgBr are summarized in runs 1 and 2,
respectively, in Table 1. In both cases, the yields are moderate; however, the stereoselectivity is
remarkably good. The ratio of (E)- and (Z)-3a was determined accurately on the basis of the
base-line separated resonances of the C-6 methyl protons and of one of the C-2 methylene
1
protons in their H NMR spectra (400 MHz, CDCl3): ꢀ 0.97 (t, J=7.2 Hz, 3H) and 2.41 (dd,
J=3.8, 13.8 Hz, 1H) for (E)-3a; ꢀ 0.90 (t, J=7.3 Hz, 3H) and 2.63 (dd, J=9.0, 13.4 Hz, 1H) for
(Z)-3a. The structures of (E)- and (Z)-3a were determined unequivocally on the basis of their 13C
NMR spectra.
Results obtained for the reactions of aromatic aldehydes bearing electron-donating or electron-
withdrawing substituents with Me3B, generated from BCl3 and MeLi, are summarized in runs 3±7
in Table 1. Generally, the stereoselectivity is quite satisfactory, providing (E)-3 in high preference
over (Z)-3 [(E)-3:(Z)-3>13:1]. The yield is also excellent, except that in run 7. The reason for the
fall in the yield for the reaction of p-bromobenzaldehyde (1f) is not clear at present; no trace
amount of 3-methyl-1-p-tolyl-3-hexenol, the product being expected to be produced from 3f
through substitution of Me for Br (the Kumada-Tamao coupling reaction), was detected in the
reaction mixture.
Aliphatic aldehydes underwent the three-component connection reaction with the similar ease
and eciency (runs 8 and 9, Table 1). In these cases, the E-selectivity turned out to be almost
1
perfect and neither (Z)-3g nor (Z)-3h was detected in the H and 13C NMR spectra of the
products isolated by ¯ash column chromatography.

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Table 1
Ni0-catalyzed (E)-selective three-component connection reaction of Me3B, isoprene, and aldehydes 1a
The reaction may proceed via a similar mechanism to that proposed for the three-component
connection reaction of Me2Zn, isoprene and benzaldehyde, as depicted in Scheme 1.2 Among the
steps, the particular step involving the methyl group transfer from B to Ni2+, i.e. leading oxy-p-
allylnickel(II) intermediate I to methyl-p-allylnickel(II) intermediate II, remains speculative at
present. Many precedents indicate that a methyl (or alkyl) group is a typical substituent of
organometalloids and their ate complexes (B,4 Si,5 Sn6) that can be transmetallated only with
great diculty. In fact, Kobayashi et al.7 have shown that only the aryl and vinyl groups of such ate
complexes as aryl(Me)B(OR)2 and vinyl(Me)B(OR)2 are selectively transferred onto p-allylnickel(II)

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Scheme 1.
intermediates. Furthermore, our attempts to use Ph3B (THF solution, Aldrich) as a phenylating
agent and Me4B^M+ as a methylating agent for the present three-component connection reaction
all met with failure. The former reaction did not furnish the expected product at all, and the latter
reaction provided 3a in low yield: 18% with Me4B^Li+ (room temperature for 21 h); 18% with
Me4B^Mg2+Br^ (room temperature for 24 h) under otherwise identical conditions, shown in
footnote a, Table 1. Nevertheless, we still favor the mechanism involving I and II as intermediates
(Scheme 1).8 In an intermediate I, electron donation from oxygen to B, an ecient orbital overlap
between the B Me bond, and an empty orbital on Ni2+ that lie in close proximity to each other
might well cooperate to promote the methyl group migration from B to Ni2+.9,10 Reductive
elimination through syn-II and anti-II that equilibrate to each other via a p±s mechanism might
provide (E)-3 and (Z)-3, respectively, and at the same time regenerate Ni0 as well. The selective
formation of (E)-3 might owe its origin to the higher thermodynamic stability of syn-II over anti-II,
which is suggested by molecular modeling studies.
Acknowledgements
Financial support from the Ministry of Education, Science, Sports and Culture, Japanese
Government, Grant-in-Aid for Scienti®c Research B, is acknowledged.
References
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MHz, CDCl3) ꢀ 0.97 (t, J=7.2 Hz, 3H), 1.69 (s, 3H), 2.06 (quint, J=7.2 Hz, 2H), 2.31 (dd, J=9.7, 13.8 Hz, 1H),
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6793
C13H18O: 190.1358; found m/z (relative intensity): 190.1359 (M+, 6), 107 (100). (Z)-3-Methyl-1-phenyl-3-hexen-1-
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