Regioselective allylzincation of alkenylboronate

Article abstract of DOI:10.1021/ol0164637

(Formula Presented) Boryl substitution on an olefin activates the olefinic double bond toward addition of an organozinc reagent. Addition of an allylic zinc reagent to an alkenylboronate thus takes place smoothly to afford a variety of gem-zincio/boryl species. Theoretical studies with density functional calculations on the reaction pathway revealed that the reaction proceeds via a zincio-ene reaction rather than a bora-Claisen rearrangement.

Full text of DOI:10.1021/ol0164637

ORGANIC
LETTERS
2
001
Vol. 3, No. 20
137-3140
Regioselective Allylzincation of
Alkenylboronate
3
†
Masaharu Nakamura, Kenji Hara, Takuji Hatakeyama, and Eiichi Nakamura*
Department of Chemistry, The UniVersity of Tokyo, Hongo, Bunkyo-ku,
Tokyo 113-0033, Japan
nakamura@chem.s.u-tokyo.ac.jp
Received July 20, 2001
ABSTRACT
Boryl substitution on an olefin activates the olefinic double bond toward addition of an organozinc reagent. Addition of an allylic zinc reagent
to an alkenylboronate thus takes place smoothly to afford a variety of gem-zincio/boryl species. Theoretical studies with density functional
calculations on the reaction pathway revealed that the reaction proceeds via a zincio-ene reaction rather than a bora-Claisen rearrangement.
Among various examples of activation of an alkene toward
organometallic addition across the olefinic double bond,
replacement of the alkenyl hydrogen atom with a metal or a
metalloid atom has been used as an effective protocol and
13 element substitution on the carbometalation reaction.4
Here we report that an alkenylboronate 1 can serve as a
versatile substrate for carbometalation reaction, in which an
allylic zinc reagent reacts with the olefin to afford syntheti-
cally useful geminal Zn/B organometallic species.
Scheme 1 depicts two possible reaction pathways in the
3
5,6
has provided a unique route to synthesis of a variety of sp -
geminal organodimetallics.1 While a Group 14 metal
,2
substituent on an olefin has long been known to electro-
3
philically activate the olefin toward organometallic addition,
few examples have been reported about the effect of Group
Scheme 1. Organometallic Addition to Vinylboron Compound
†
Present address: Department of Chemistry, Hokkaido University,
Sapporo, Japan.
(
1) Marek, I.; Normant, J.-F. Chem. ReV. 1996, 96, 3241-3267.
(2) (a) Nakamura, M.; Hara, K.; Sakata, G.; Nakamura, E. Org. Lett.
1
999, 1, 1505-1507. (b) Nakamura, E.; Sakata, G.; Kubota, K. Tetrahedron
Lett. 1998, 39, 2157-2158. (c) Nakamura, E.; Kubota, K. Tetrahedron Lett.
1
Chem. Soc. 1997, 119, 5457-5458. (e) Kubota, K.; Nakamura, E. Angew.
Chem., Int. Ed. Engl. 1997, 36, 2491-2493. (f) Kubota, K.; Nakamura,
M.; Isaka, M.; Nakamura, E. J. Am. Chem. Soc. 1993 115, 5867-5868.
997, 38, 7099-7102. (d) Nakamura, E.; Kubota, K.; Sakata, G. J. Am.
(3) For representative examples, see: (a) Itami, K.; Mitsudo, K.; Yoshida,
J.-i. Angew. Chem., Int. Ed. 2001, 40, 2337-2339. (b) Nakamura, M.; Inoue,
T.; Sato, A.; Nakamura, E. Org. Lett. 2000, 2, 2193-2196. (c) Tamao, K.;
Kanatani, R.; Kumada, M. Tetrahedron Lett. 1984, 25, 1913-1916. (c)
Buell, G. R.; Corriu, R.; Christian, G.; Spialter, L. J. Am. Chem. Soc. 1970,
addition of a nucleophilic organometallic reagent to a
vinylboronate. Our strategy to employ an allylic zinc reagent
9
2, 7424-7428. (d) Stober, M. R.; Michael, K. W.; Speier, J. L. J. Org.
Chem. 1967, 32, 2740-2744.
1
0.1021/ol0164637 CCC: $20.00 © 2001 American Chemical Society
Published on Web 09/13/2001

to achieve selective carbometalation was inspired by our
recent theoretical studies, by which the pathways of the
addition of allylic zinc reagents to various vinylmetal species
Table 1. Addition of Allylic Zinc Reagents to Alkenylboronate
1
7
were proved for the first time. We expected that the
propensity of the zinc atom to assist the carbometalation
8
reaction would direct the allylic zinc reagent to the CdC
double bond rather than to the boron atom.
The addition of an allylic zinc reagent 2 to the alkenyl-
boronate (1a and b) was found to take place smoothly to
afford an organoboronate 4 under mild conditions. Upon
electrophilic trapping of an intermediary Zn/B organodi-
metallic species 3, a variety of organoboronates were
obtained in fair to excellent yield (Scheme 2). The product
Scheme 2. Allylzincation of Vinylboronate
4
′, which is a regioisomer of 4, did not form at all. The
addition of allylmagnesium bromide and allyllithium to 1
did not give the allylation product at all under the same
9
conditions. None of the desired carbometalation product was
obtained even in the reaction of 2, when the pinacol borane
moiety was replaced with a dibutoxy boryl group.
a
All reactions were performed in THF/hexane at 0-25 °C for 36-48 h
b
using 1.0-1.2 equiv of an allylic zinc reagent. SE′ regioisomer was
obtained in 11% yield. c (E)-Styrylboronate 1b was used. d The enantiomeric
Table 1 summarizes the results of the reaction between a
variety of allylic zinc reagents and alkenylboronates. The
excess was determined by chiral capillary gas chromatography after
oxidative conversion to the corresponding alcohol.
(
4) There is only one report on the carbometalation of alkenylborane, in
reaction was carried out simply by mixing a slight excess
amount of the allylic zinc reagent 2 with vinylboronate 1a
at 0-25 °C for 36-48 h. The addition reaction is much faster
with allylbutylzinc than with allylzinc bromide (entries 1 and
2). The allylbutylzinc reagent 2 was prepared by treatment
of an allylic zinc bromide with a stoichiometric amount of
which the carbolithiation reaction of 1-(dimesityl)boryl-1-silylalkenes was
examined: Cooke, M. P., Jr.; Widener, R. K. J. Am. Chem. Soc. 1987,
09, 931-933. Boryl substitution activates the carbon-carbon triple bond
as well as the olefinic double bond toward intramolecular carbolithiation
1
reaction: Cooke, M. P., Jr. J. Org. Chem. 1994, 59, 2930-2931.
(
5) Knochel, P. J. Am. Chem. Soc. 1990, 112, 7431-7433.
(6) For reviews see: Pelter, A.; Smith, K.; Brown, H. C. Borane
Reagents; Katritzky, A. R., Meth-Cohn, O., Rees, C. W., Eds; Academic
Press: New York, 1998. Vaultier, M.; Carboni, B. In ComprehensiVe
Organometallic Chemistry II; Wilkinson, G., Stone, F. G. A., Abel, E. W.,
Eds; Pergammon: Oxford, 1995; Vol. 11, pp 191-276.
1
0
butyllithium. Butylmethallylzinc also added to vinylbor-
onate 1 to give the allylzincation product in 87% yield (entry
3
). Note that the butyl group on the zinc atom is essential to
(7) (a) Hirai, A.; Nakamura, M.; Nakamura, E. J. Am. Chem. Soc. 2000,
1
22, 11791-11798. (b) Hirai, A.; Nakamura, M.; Nakamura, E. J. Am.
Chem. Soc. 1999, 121, 8665-8666. See also: (c) Marek, I.; Schreiner, P.
R.; Normant, J. F. Org. Lett. 1999, 1, 929-931.
(10) Typical Procedure. To a solution of allylzinc bromide (0.902 M
in THF, 1.33 mL, 1.2 mmol) was added BuLi (1.60 M in hexane, 0.750
mL, 1.2 mmol) at 0 °C, 2-vinyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
(0.174 mL, 1.0 mmol) was added at 0 °C, and the mixture was gradually
warmed to room temperature. After 36 h, aqueous hydrochloric acid (6 M,
1.0 mL) was added at 0 °C, and the mixture was warmed to 25 °C. The
aqueous layer was extracted three times with Et2O. The combined organic
extracts were washed with a 30% aqueous potassium sodium tartrate and
(8) (a) Gaudemar, M. C. R. S e´ ances Acad. Sci., S e´ r. C 1971, 273, 1669-
1
1
672. (b) Knochel, P.; Normant, J. F. Tetrahedron Lett. 1986, 27, 1039-
042.
(
9) The reaction with allylmagnesium bromide and allyllithium resulted
largely in the loss of the material with some recovery of the vinylboronate
8% and 30%, respectively).
(
3138
Org. Lett., Vol. 3, No. 20, 2001

achieve smooth conversion as we previously reported for
the related carbozincation reactions.2
showed that the Zn/B product can form via two independent
pathways, carbometalation (zincio-ene reaction) and borate
paths (followed by bora-Claisen rearrangement) (Scheme 1).
Transmetalation of the allyl group from zinc to boron was
found to give the borate complex, which is 9.6 kcal/mol
higher in energy than the starting material, a complex
between vinylboronate and allylmethylzinc. The transition
structures of the two paths are shown in Figure 1. The zincio-
The addition of a γ-substituted allylic zinc reagent (entries
-6), as well as γ,γ- and â,γ-disubstituted allylic zinc
4
reagents (entries 7 and 8) to the vinylboronate 1 proceeded
smoothly under the same conditions. The C-C bond
formation took place exclusively at the γ-position of the
allylic zinc reagents in 69-96% yield.11 The reaction of
styrylborane 1b with butylmethallylzinc gave the regioisomer
12
4
as an exclusive product. As shown in entry 10, installation
of chiral bis-oxazoline ligand in place of the butyl group
resulted in chirality induction (44% ee). Further experimenta-
tion is clearly necessary to obtain acceptable selectivity and
reactivity.
Through suitable functional group manipulations, the
geminal Zn/B moiety in intermediates 3 can be transformed
to useful functional groups. The alkenylboronate molecule,
hence, serves as a useful acceptor synthon of a functionalized
two-carbon unit. Thus, intermediary zinc compound 5 could
be trapped with a carbon electrophile, and the resulting
boronate product afforded the secondary alcohol 6 upon
oxidation with basic hydrogen peroxide in 83% yield (eq
1). Oxidation with molecular oxygen after the addition of 1
equiv of zinc bromide to the intermediate 7 allows direct
transformation to aldehyde 8 (eq 2).13
Figure 1. Transition structures of allylzincation of vinylboronate
(B3LYP/631A).
ene transition state (9) is of lower energy than the bora-
Claisen rearrangement TS (10) by ca. 10.5 kcal/mol.
Molecular orbital analysis indicated that the zincio-ene
transition state is stabilized by the interaction between the
forming C-Zn σ bond and the boron’s vacant p orbital.16
In summary, the present study revealed that the boryl
substituent activates an olefin toward carbozincation reaction
and provides an efficient method for the synthesis of a variety
of geminal Zn/B organodimetallic species. Experiments and
theory suggested that the formation of a stable borate
complex can be avoided by the combined use of an allylic
zinc reagent and the bulky pinacol borane substituent.
Density functional theoretical studies on the reaction
pathway of the allylzincation at the B3LYP/631A level
1
4,15
then with a saturated sodium chloride solution, dried over sodium sulfate,
and concentrated. The residual colorless oil was pure by TLC or NMR
(
0.161 g, 82%, Rf ) 0.24, 5% EtOAc in hexane). Further purification was,
if necessary, carried out by silica gel chromatography.
11) Compare: Kubota, K.; Mori, S.; Nakamura, M.; Nakamura, E. J.
Am. Chem. Soc. 1998, 120, 13334-13341.
12) In the reaction of 1-boryl-1-propene, the regioselectivity as to the
(
(
allylic zinc reagent eroded and gave a nearly 1:1 mixture of R- and
γ-regioisomers. The diastereoselectivity as to the newly formed C-C bond
was also very low.
(13) The oxidation was performed according to Knochel’s procedure with
slight modification: Knochel, P. Tetrahedron Lett. 1988, 29, 6697-6700.
See also ref 2a.
Acknowledgment. This work is supported by Mombu-
kagakusho and a Grant-in-Aid for Scientific Research on
(14) The DFT study was conducted with a model system that consists
of allylmethylzinc and vinylborinate ethylene glycol ester. All theoretical
calculations were carried out with the Gaussian 98 program.15 Geometry
optimization was performed with the hybrid B3LYP density functional by
using Ahlrichs' SVP basis set for Zn and 6-31+G(d) basis set for the rest
D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Cioslowski, J.;
Ortiz, J. V.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi,
I.; Gomperts, R.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.;
Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challacombe, M.; Gill, P. M.
W.; Johnson, B. G.; Chen, W.; Wong, M. W.; Andres, J. L.; Head-Gordon,
M.; Replogle, E. S.; Pople, J. A. Gaussian 98, revision A.7; Gaussian,
Inc.: Pittsburgh, PA, 1998.
(
denoted as B3LYP/631A). The basis sets are implemented in the program.
(15) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Zakrzewski, V. G.; Montgomery, J. A., Jr.;
Stratmann, R. E.; Burant, J. C.; Dapprich, S.; Millam, J. M.; Daniels, A.
D.; Kudin, K. N.; Strain, M. C.; Farkas, O.; Tomasi, J.; Barone, V.; Cossi,
M.; Cammi, R.; Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.;
Ochterski, J.; Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick,
(16) Theoretical details including discussion on the electronic properties
of the transition structures will be reported in a full paper.
Org. Lett., Vol. 3, No. 20, 2001
3139

Priority Area (no. 403-11166220, Molecular Physical Chem-
istry) Generous allotment of computational time from the
Institute for Molecular Science, Okazaki, Japan and Intel-
ligent Modeling Laboratory, The University of Tokyo is
gratefully acknowledged.
Supporting Information Available: Experimental pro-
cedures and physical properties of new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL0164637
3140
Org. Lett., Vol. 3, No. 20, 2001