Contrasteric stereochemical dictation of the cyclobutene ring-opening reaction by a vacant boron p orbital

Article abstract of DOI:10.1021/ja043979n

Cyclobutene, having a pinacolatoboryl group at the 3-position, was prepared by the reaction of trimethyl borate with a cyclobutenyl anion, which was generated by reductive lithiation of 3-(phenylselenyl)cyclobutene. Its thermal ring-opening reaction provi

Full text of DOI:10.1021/ja043979n

Published on Web 01/11/2005
Contrasteric Stereochemical Dictation of the Cyclobutene Ring-Opening
Reaction by a Vacant Boron p Orbital
Masahiro Murakami,* Ippei Usui, Munehiro Hasegawa, and Takanori Matsuda
Department of Synthetic Chemistry and Biological Chemistry, Kyoto UniVersity, Katsura, Kyoto 615-8510, Japan
Received October 3, 2004; E-mail: murakami@sbchem.kyoto-u.ac.jp
Scheme 1. Synthesis of 3-(Pinacolatoboryl)cyclobutene (1)a
The torquoselectivity of the thermal ring-opening reaction of
cyclobutene has been a subject of fundamental importance in
organic and theoretical chemistry.1 Houk’s theory states that an
electron-accepting substituent at the 3-position prefers inward
rotation.2 Delocalization of electron density of the HOMO of the
opening cyclobutene skeleton to the electron-accepting substituent
stabilizes the inward transition state. The electronic stabilization
can outweigh or counterbalance the steric congestion developing
during inward rotation.3 For example, a formyl group can accept
electron density into its antibonding π* orbital and thus rotates with
high inward selectivity.3a We recently discovered the interesting
preference of silyl groups to rotate inward.4,5 Although silicon is
a Reagents and conditions: (a) Cl3CCOCl, Zn-Cu, 1,2-dimethoxyethane,
Et2O, room temperature. (b) Zn-Cu, THF, H2O (54%, two steps). (c)
TsNHNH2, EtOH, room temperature (91%). (d) n-BuLi, hexane-N,N,N’,N’-
tetramethylethylenediamine (10:1), -78 °C to room temperature, then H2O,
-78 °C (61%). (e) PhSeCl, CH2Cl2, -78 °C to room temperature. (f) TBAF,
THF, -78 °C to room temperature (45% from 2). (g) lithium naphthalenide,
THF, -78 °C. (h) i) B(OMe)3, -78 °C, ii) H3O+, -78 °C, iii) pinacol
(32% from 3).
less electronegative than carbon, the antibonding σ* orbital of a
silicon-carbon linkage is energetically low-lying and able to accept
electron density, favoring the inward transition state.4a,6,7
A trisubstituted organoborane has an energetically low-lying
vacant p orbital, and the vacant orbital can accept electron density
from another molecule (Lewis acid-base complexation) or inside
the molecule (delocalization or conjugation). In 1985, Rondan and
Houk predicted that a boryl substituent would have a strong
preference for inward rotation.2 The inward transition state of
3-(BMe2)cyclobutene was calculated to be lower than the outward
transition state by as much as 10.5 kcal/mol.8 Remarkably, there
has been no experimental validation of this basic issue, possibly
due to the difficulty in the preparation of 3-borylcyclobutenes. We
now report the synthesis of 3-(pinacolatoboryl)cyclobutene (1) and
its rotational behavior.9
At first, we envisaged that the nucleophilic substitution reaction
of a boronic acid derivative with a cyclobutenyl anion would
provide a straightforward synthetic access to 3-borylcyclobutene.
However, attempts to generate cyclobutenyllithium by reductive
lithiation of 3-halocyclobutene were unsuccessful. Thus, we
developed an alternative route to 3-borylcyclobutene 1 via 3-sele-
nylcyclobutene. The synthesis was achieved in eight steps starting
from dimethylphenylvinylsilane (Scheme 1). [2 + 2] Cycloaddition
with dichloroketene, followed by dechlorination with zinc-copper
couple furnished 3-(dimethylphenylsilyl)cyclobutanone. The cy-
clobutanone was transformed to the corresponding tosylhydrazone,
which was then subjected to the Shapiro olefination reaction10
affording 3-(dimethylphenylsilyl)cyclobutene (2). Treatment of the
cyclobutene 2 with phenylselenenyl chloride gave 2-chloro-1-silyl-
3-selenylcyclobutane as a diastereomeric mixture, which upon
treatment with tetrabutylammonium fluoride (TBAF) underwent
elimination of the chloro and silyl groups to afford 3-(phenyl-
selenyl)cyclobutene (3).11 Reductive removal of the selenyl group
with lithium naphthalenide produced the cyclobutenyl anion 4.12,13
Addition of trimethyl borate to the anion 4 followed by treatment
with pinacol furnished the 3-(pinacolatoboryl)cyclobutene (1). Thus,
a method for the generation of cyclobutenyllithium has been
developed via reductive cleavage of a selenium-carbon bond. This
procedure also provides a facile route for the nucleophilic incor-
poration of cyclobuten-3-yl groups into various organic skeletons.
The cyclobutene 1 thus obtained was heated in toluene-d8 in the
presence of a small amount of galvinoxyl to suppress olefin
isomerization by radical pathways.14 The ring-opening reaction of
1 in the dark proceeded at 92 °C with a rate of k ) 1.0 h-1 and
was almost complete after 4 h (eq 1). Exclusive formation of (Z)-
1-borylbuta-1,3-diene 5 was observed by 1H NMR up to 80%
conversion, beyond which the (E)-isomer gradually appeared by
isomerization of (Z)-5 initially formed. The kinetics of the ring
opening were investigated at varying temperatures, and activation
parameters k ) 1014.5 exp(-24.3/RT) h-1 were obtained from the
Arrhenius plot.
Thus, appending a boryl group at the 3-position of cyclobutene
had a huge effect on the reactivity of the parent cyclobutene
skeleton, permitting the electrocyclic ring-opening reaction at
temperatures as low as 70 °C. Furthermore, the more sterically
demanding inward rotation occurred exclusively. These results can
be understood by invoking the electronic participation of the boryl
substituent, as theoretically predicted.2 In the inward transition state,
the vacant p orbital accepts electron density from the breaking
distorted σ orbital, that is the HOMO of the parent cyclobutene
skeleton (Figure 1). This electron delocalization provides significant
stabilization to the inward transition state.
9
1366
J. AM. CHEM. SOC. 2005, 127, 1366-1367
10.1021/ja043979n CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Figure 1. Electron-accepting interaction of the vacant boron p orbital with
the HOMO in the inward transition state.
Scheme 2. Synthesis of 3-Boryl-3-silylcyclobutene 6
Acknowledgment. This paper is dedicated to Professor Iwao
Ojima on the occasion of his 60th birthday.
Supporting Information Available: Experimental details and
selected spectral data for new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
References
(1) (a) Durst, T.; Breau, L. In ComprehensiVe Organic Synthesis; Trost, B.
M., Fleming, I., Paquette, L. A., Eds.; Pergamon: Oxford, 1991; Vol. 5,
pp 675-697. (b) Dolbier, W. R., Jr.; Koroniak, H.; Houk, K. N.; Sheu,
C. Acc. Chem. Res. 1996, 29, 471-477.
(2) Rondan, N. G.; Houk, K. N. J. Am. Chem. Soc. 1985, 107, 2099-2111.
(3) (a) Rudolf, K.; Spellmeyer, D. C.; Houk, K. N. J. Org. Chem. 1987, 52,
3708-3710. (b) Piers, E.; Lu, Y.-F. J. Org. Chem. 1989, 54, 2267-2268.
(c) Jefford, C. W.; Bernardinelli, G.; Wang, Y.; Spellmeyer, D. C.; Buda,
A.; Houk, K. N. J. Am. Chem. Soc. 1992, 114, 1157-1165. (d) Niwayama,
S.; Houk, K. N. Tetrahedron Lett. 1993, 34, 1251-1254 and references
therein.
(4) (a) Murakami, M.; Miyamoto, Y.; Ito, Y. Angew. Chem., Int. Ed. 2001,
40, 189-190. (b) Murakami, M.; Miyamoto, Y.; Ito, Y. J. Am. Chem.
Soc. 2001, 123, 6441-6442. (c) Murakami, M.; Hasegawa, M. Angew.
Chem., Int. Ed., 2004, 43, 4874-4876.
(5) For studies on the ring-opening reaction of 3-stannylcyclobutene, see:
Murakami, M.; Hasegawa, M.; Igawa, H. J. Org. Chem. 2004, 69, 587-
590.
We have demonstrated that both boryl and silyl groups prefer to
rotate inward in the cyclobutene ring-opening reaction due to
electronic reasons despite the steric congestion that is generated. It
is of much interest to compare the magnitude of the inward
preferences of boryl and silyl groups by experiment. Thus, we
prepared cyclobutene 6 having both boryl and silyl groups at the
3-position according to the procedure developed by Shimizu and
Hiyama.15 R-Bromoallyllithium, generated in situ from 3-bromo-
1-phenylcyclobutene and lithium diisopropylamide (LDA), was
reacted with (dimethylphenylsilyl)pinacolborane in THF, and the
desired 3-boryl-3-silylcyclobutene 6 was obtained in 59% yield
(Scheme 2).
The ring-opening reaction of the cyclobutene 6 proceeded at 100
°C with a rate of k ) 1.1 h-1 affording a mixture of E- and Z-1-
boryl-1-silylbuta-1,3-diene 7 (eq 2). The diene (E)-7, in which the
boryl substituent had rotated inward, predominated over (Z)-7 in a
ratio of 85:15.16 An Arrhenius plot provided activation parameters
k ) 1014.8 exp(-25.1/RT) h-1. The stereochemical outcome
demonstrates that the boryl group has a stronger preference for
inward rotation than the silyl group and that the boron vacant p
orbital accepts electron density more efficiently than the antibonding
σ* orbital of silicon in the transition state.
(6) (a) Lee, P. S.; Zhang, X.; Houk, K. N. J. Am. Chem. Soc. 2003, 125,
5072-5079. (b) Mori, S.; Shindo, M. Org. Lett. 2004, 6, 3945-3948.
(7) For another explanation assuming geminal σ bond participation, see:
Yasui, M.; Naruse, Y.; Inagaki, S. J. Org. Chem. 2004, 69, 7246-7249.
(8) Niwayama, S.; Kallel, E. A.; Spellmeyer, D. C.; Sheu, C.; Houk, K. N. J.
Org. Chem. 1996, 61, 2813-2825.
(9) For the effects of a boryl substituent on the ring-closing reaction of
vinylallene, see: Murakami, M.; Ashida, S.; Matsuda, T. J. Am. Chem.
Soc. 2004, 126, 10838-10839.
(10) Shapiro, R. H. Org. React. 1976, 23, 405-507.
(11) Nishiyama, H.; Itagaki, K.; Sakuta, K.; Itoh, K. Tetrahedron Lett. 1981,
22, 5285-5288.
(12) Krief, A.; Nazih, A. Tetrahedron Lett. 1995, 36, 8115-8118.
(13) Reductive lithiation from the corresponding phenylthio derivative was
unsuccessful. Cohen, T.; Guo, B.-S. Tetrahedron 1985, 42, 2803-2808.
(14) In the absence of galvinoxyl, a facile isomerization of (Z)-5 to (E)-5 took
place to afford a mixture of the E- and Z-dienes (e.g. 45:55 with 54%
conversion after heating at 80 °C for 1 h).
In summary, we have developed a valuable preparative method
for the generation of cyclobutenyl anion 4 and verified the exclusive
inward rotation of a boryl substituent in the cyclobutene ring-
opening reaction. It was also experimentally demonstrated that
boron is more powerful than silicon in terms of directing inward
rotation.
(15) Shimizu, M.; Kitagawa, H.; Kurahashi, T.; Hiyama, T. Angew. Chem.,
Int. Ed. 2001, 40, 4283-4286. Although it was reported that the reaction
of R-substituted allylic chloride failed to occur, 3-bromocyclobutene
successfully produced 6.
(16) The E stereochemistry of the major product was unambiguously confirmed
by 1H NMR NOE experiments.
JA043979N
9
J. AM. CHEM. SOC. VOL. 127, NO. 5, 2005 1367