DOI: 10.1002/chem.201404587
Communication
&
Asymmetric Catalysis
Catalytic Asymmetric Synthesis of Alkynyl Aziridines: Both
Enantiomers of cis-Aziridines from One Enantiomer of the Catalyst
Yong Guan,[a] Maria P. Lꢀpez-Alberca,[a] Zhenjie Lu,[a] Yu Zhang,[a] Aman A. Desai,[a]
Aniruddha P. Patwardhan,[a] Yijing Dai,[a] Mathew J. Vetticatt,*[b] and William D. Wulff*[a]
with aldehydes[13] and sulfonium ylides with imines.[14] Early
Abstract: Alkynyl aziridines can be obtained from the cat-
methods include dehydrohalogenantion of a-bromoalkenyl
alytic asymmetric aziridination (AZ reaction) of alkynyl
aziridines[15] and nitrene addition to alkenes.[16] A popular
imines with diazo compounds in high yields and high
method has been the addition of alkynyl organometallics to a-
chloroimines[17] and to a-epoxy imines.[18] Access to alkynyl
asymmetric inductions mediated by a chiral boroxinate or
BOROX catalyst. In contrast to the AZ reaction with aryl-
aziridines can be reliably realized by the ring closure of w-hal-
and alkyl-substituted imines, alkynyl imines react to give
oallenyl methyl amines.[19] An attractive approach to the syn-
cis-substituted aziridines with both diazo esters and diazo
thesis of alkynyl aziridines is the addition of g-haloallenyl zinc
acetamides. Remarkably, however, the two diazo com-
reagents to imines.[20] There is also the straightforward option
pounds give different enantiomers of the cis-aziridine
of ring-closure of a b-aminoalcohol which was employed after
from the same enantiomer of the catalyst. Theoretical con-
a base-promoted aza-Darzen reaction failed.[12a] A very effective
siderations of the possible transition states for the enan-
method has been reported involving a Brønsted acid catalyzed
tiogenic step reveal that the switch in enantiomers results
addition of a diazo compound with an alkynyl imine.[12b] With
from a switch from Si-face to Re-face addition to the
all of the options at ones avail, there are nonetheless, a paucity
imine, which in turn is related to a switch from reaction
of catalytic asymmetric methods. While there are a number of
with an E-imine in the former and a Z-isomer of the imine
reports of chiral catalysts used in the preparation of alkynyl
in the latter.
aziridines from the addition of a nitrene unit to an alkene, the
scope is severely underdeveloped since all reports describe
a single substrate, 1-phenyl-3-buten-1-yne.[21]
The chemistry of alkynyl aziridines has only been explored in
any serious way in the last ten years or so.[1] Synthetic applica-
tions have included conjugate ring opening,[2,3] direct ring-
opening at the propargylic carbon,[4–7] domino cyclization/ring
expansions,[8] isomerization to pyrroles,[9] gold-catalyzed rear-
rangements,[10] and palladium- and indium-mediated alkylative
reductive opening.[11] Many of these reactions have been em-
ployed in the synthesis of natural products including the usti-
loxins,[6c–f] mitomycin C,[12] phomopsin B,[6b] saxitoxinol,[5c] lyser-
gic acid,[11c] lysergol,[11c] isolysergol,[11c] and saxitoxin.[5b]
We have developed an asymmetric catalytic synthesis of
aziridines from the reaction of imines and diazo com-
pounds.[22–25] The chiral core of the catalyst for these reactions
are the vaulted biaryl ligands VAPOL and VANOL.[26] The cata-
lyst has been identified as the boroxinate 4 or 5 which is as-
sembled in situ from the ligand and B(OPh)3 only upon addi-
tion of the imine substrate (Scheme 1).[25b,27] The catalytic
asymmetric aziridination is general for a variety of imine sub-
strates providing access to aziridines with electron-rich and
electron poor aryl and heteroaryl substituents as well as 18, 28,
and 38 alkyl substituents bearing a range of functional groups.
High yields, diastereoselectivity and enantioselectivity can be
achieved with both cis- and trans-aziridines; the former with
diazoacetates[22] and the latter with diazoacetamides.[28] The
(S)-VANOL- or (S)-VAPOL-derived catalysts will deliver cis-aziri-
dines via addition to the Si-face of the imine and trans-aziri-
dines via Re-face addition to the imine. The present study finds
that the same reaction with alkynyl imines with the same anti-
pode of the catalyst gives cis-aziridines with both diazoace-
tates and diazoacetamides, but as opposite enantiomers
(Scheme 1). The results of computational studies suggests that
this enantiomeric switch is due to the preferred reaction of the
E-isomer of the imine with diazoacetates and the Z-isomer of
the imine with diazoacetamides.
Previous syntheses of alkynyl aziridines encompass a cornu-
copia of methods including reaction of guanidinium ylides
[a] Dr. Y. Guan, Dr. M. P. Lꢀpez-Alberca, Dr. Z. Lu, Dr. Y. Zhang, Dr. A. A. Desai,
Dr. A. P. Patwardhan, Y. Dai, Prof. W. D. Wulff
Department of Chemistry
Michigan State University
East Lansing, MI 48824 (USA)
Fax: (001)517-3353-1793
dex.htm
[b] Prof. M. J. Vetticatt
Department of Chemistry
Binghamton University
Binghamton, NY 13902 (USA)
Our initial finding was that the success of this catalytic asym-
metric aziridination reaction did not translate to imines from
alkynyl aldehydes. For example, the reaction of the imine 13a
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201404587.
Chem. Eur. J. 2014, 20, 13894 – 13900
13894
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