Angewandte
Communications
Chemie
Alkene Synthesis
Stereospecific Synthesis of Alkenes by Eliminative Cross-Coupling of
Enantioenriched sp3-Hybridized Carbenoids
Abstract: 1-Aryl-1,2-dialkylethenes were generated by
a sequence of electrophilic substitution, 1,2-metalate rearrange-
ment, and b-elimination initiated by the addition of enantioen-
riched a-(carbamoyloxy)alkylboronates to enantioenriched
lithiated carbamates. The carbenoid stereochemical pairing
[i.e., “like” = (S)+(S) or “unlike” = (S)+(R)] and the elimi-
nation mechanism (syn or anti), not substituent effects,
determined the configuration of the trisubstituted alkene
target. For example, (Z)-2,5-diphenyl-2-pentene was produced
in 70% yield with E/Z = 5:95 by a like combination of Li and
B carbenoids and syn (thermal) elimination whereas the
E isomer was obtained in the same yield with E/Z > 98:2 by
an otherwise identical process involving an unlike stereochem-
ical pairing. The concept elaborated overcomes an intrinsic
limitation of traditional strategies for direct connective alkene
synthesis, which cannot realize meaningful stereochemical bias
unless the alkene substituents are strongly differentiated.
(Scheme 1).[6] No biasing features are required within the
substituents (R1–R4) to achieve fully controlled alkene
formation with this concept. The process is trivially regiospe-
cific, and stereochemical information encoded within the two
carbenoid subunits is translated via a sequence of three
stereospecific processes [electrophilic substitution (1 + 2!3),
1,2-metalate rearrangement (3!4), and b-elimination (4!
5)] into any desired configuration of the target alkene 5.
Herein, the realization of this eliminative cross-coupling
approach for the synthesis of a series of trisubstituted alkenes
belonging to the styrene class is reported.[7]
T
he carbon–carbon double bond is of fundamental impor-
tance, and molecules containing some type of pCC system are
widespread and have broad utility. In general, carbon–carbon
double bonds are stereogenic and/or decorated non-sym-
metrically, and so synthetic methods designed to access them
should be capable of both stereo- and regiocontrol.[1] In spite
of this fact, conventional direct methods for the preparation
of alkenes, the most common class of compounds containing
pCC bonds, do not wholly address selectivity issues. For
example, carbonyl olefination based approaches are regio-
specific but good stereocontrol is dependent on the alkene
substituents being adequately differentiated by steric or
electronic factors.[2] As a consequence, excellent stereoselec-
tivity is only guaranteed for 1,2-disubstituted alkene targets,
and the stereocontrolled synthesis of tri- and tetrasubstituted
examples remains a challenge.[3] When alkenes are prepared
by alkyne elementometalation,[4] stereospecificity is achieved
but regiocontrol is dependent on the substituents being again
distinguished in some special way, and poor selectivity is
anticipated for generic internal alkynes.[5] To overcome the
limitations of existing strategies, a connective synthesis of
alkenes was envisioned by eliminative cross-coupling of
Scheme 1. Eliminative cross-coupling of enantioenriched carbenoids
for the synthesis of alkenes.
The formation of symmetric alkenes by eliminative
“dimerization” (i.e., homocoupling) of more reactive carbe-
noids is an often observed side reaction.[8] Hodgson and co-
workers deliberately exploited this phenomenon to make
2-buten-1,4-diol derivatives by homocoupling of 1-lithiooxir-
anes and demonstrated that the E/Z ratio of the olefin
product was dependent on the enantiopurity of the carbenoid,
as anticipated.[9] The synthesis of non-symmetric alkenes by
cross-coupling of racemic carbenoids has been occasionally
explored; however, these approaches offer poor, or else not
generalizable, stereoselectivity.[10] In a seminal effort that goes
a long way to validate the premise of the above scheme,
Matteson and co-workers described the cross-coupling of
enantioenriched a-chloroalkylboronates and enantioenriched
Stille-type carbanions to afford stereodefined contiguous
stereodiad motifs bearing vicinal boron and oxygen substitu-
ents [Eq. (1); MOM = methoxymethyl].[11] Elimination was
not pursued; however, treatment of the b-oxyboronate
enantioenriched sp3-hybridized carbenoids
1
and
2
[*] Z. Wu, X. Sun, K. Potter, Y. Cao, Dr. L. N. Zakharov,
Prof. Dr. P. R. Blakemore
Department of Chemistry, Oregon State University
Corvallis, OR 97331 (USA)
E-mail: paul.blakemore@oregonstate.edu
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
Angew. Chem. Int. Ed. 2016, 55, 1 – 6
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!