of 2-B(pin)-substituted allylic alcohols is catalyzed by
7
OV(acac)2 and generates the product with excellent
Table 1. One-Pot Synthesis of 2-B(pin) Allylic Alcohols via
1-Alkenyl-1,1-heterobimetallic Intermediates
diastereoselectivity (>20:1). Subsequent oxidation of the
BꢀC bond in the presence of NaOH and led to formation
of the anti-2-keto-1,3-diols in good yields (55ꢀ96%).5e
This method represents a new synthesis of synthetically
important keto diols.8
allylic
yield
(%)a
entry
R
R0
alcohol
Scheme 1. Control of Chemoselectivity in Oxidation of B(pin)-
Substituted Allylic Alcohols
1
n-Bu
i-Bu
Bn
Ph
Ph
Ph
Ph
Ph
Ph
1a
1b
1c
1d
1e
1f
70
76
68
69
81
62a
88
81
85
77
61b
79
2
3
4
Cy
5
i-Pr
6
Ph(Me)CH2-
7
i-Pr
4-C6H4-OMe
4-C6H4-Cl
n-Bu
1g
1h
1i
8
i-Pr
9
Cy
10
11
12
i-Pr
n-Bu
1j
PhCH3(CH)-
Bn
n-Bu
1k
1l
Cyclohexenyl
a Isolated yield. b dr = 7:1 (determined by 1H NMR of crude reaction
mixture); diastereomers separated by column chromatography and the
major used in subsequent reactions.
In considering other types of oxidations that could be
performed in the presence of the vinyl boronate ester, we
were attracted to aziridination. Aziridines are important
structural components present in many biologically active
natural products and are useful synthetic intermediates.9
Herein we describe the highly diastereoselective aziridina-
tion of B(pin)-substituted allylic alcohols.
For any synthetic method to be useful, the substrates
must be readily accessible. The B(pin)-substituted allylic
alcohols were prepared as previously reported in one
pot using our stereodefined 1-alkenyl-1,1-heterobimetallic
reagents.4b,5e,6 Thus, hydroboration of air-stable alkynyl-
dioxaborolanes with dicyclohexylborane and selective B to
Zn transmetalation of the vinyl-BCy2 moiety generates the
heterobimetallic intermediate. Addition of the ZnꢀC bond
to aldehydes followed by quenching furnished (E)-2-B-
(pin)-substituted allylic alcohols 1aꢀ1l in 61ꢀ88% yield
(Table 1). It is noteworthy that 2-B(pin)-substituted allylic
alcohols can be prepared on gram scale.5e
mediated by the strong oxidant PhI(OAc)2 (Table 2).11
Aziridination product 2a was not observed using PhI-
(OAc)2 in CH2Cl2.12 Instead a diastereomeric mixture of
3a was formed, presumably via aziridine ring opening
promoted by the AcOH generated during the nitrene
formation (entry 1).13 When excess K2CO3 was employed,
however, aziridine 2a was isolated in 46% yield with an
encouraging diastereoselectivity (dr = 5:1, entry 2). Chan-
ging the solvent to toluene or CH3CN led to complex
mixtures (entries 3 and 4). Other additives or bases resulted
14
in comparable diastereocontrol to K2CO3 and reduced
yields (38ꢀ45%, entries 5ꢀ7) due to formation of bypro-
duct 3a. Surprisingly, by changing the addition order by
adding PhI(OAc)2 last, aziridine 2a could be isolated in
62% yield with a good diastereomeric ratio (dr = 7:1) and
only trace amounts of 3a (2a/3a g 95:5, entry 8).
The substrate scope of this method was next examined.
As shown in Table 3, a wide range of B(pin)-substituted
allylic alcohols were evaluated under the optimized condi-
tions, providing the corresponding B(pin)-substituted
aziridines2bꢀl in good yields (59ꢀ78%) withhigh levels of
diastereoselectivity (typically g15:1). Because these pro-
ducts are prone to decompose in the presence of trace acid
or Lewis acidic silica gel, their isolation was performed by
passing a solution of the aziridine through a small pad of
Inspired by the seminal work of Che and Yudin describ-
ing a novel nitrene equivalent for aziridination of olefins,10
we investigated the reaction of B(pin)-substituted allylic
alcohol 1awith N-aminophthalimide as the nitrogen source
(7) Sharpless, K.; Michaelson, R. J. Am. Chem. Soc. 1973, 95, 6136.
(8) Enders, D.; Voith, M.; Lenzen, A. Angew. Chem., Int. Ed. 2005,
44, 1304.
€
(9) For reviews, see: (a) Muller, P.; Fruit, C. Chem. Rev. 2003, 103,
2905. (b) Aziridines and Epoxides in Organic Synthesis; Yudin, A. K., Ed.;
Wiley-VCH: Weinheim, 2006. (c) Hou, X. L.; Wu, J.; Fan, R.; Ding, C. H.;
Luo, Z. B.; Dai, L. X. Synlett 2006, 181. (d) Pellissier, H. Tetrahedron
2010, 66, 1509.
(12) Other hypervalent iodine derivatives were also tested, but less
satisfactory results were obtained. See SI for details.
(13) For the beneficial effect of the in situ generation of AcOH under
these reaction conditions in a Pd-catalyzed aminoacetoxylation of
alkenes, see: Liu, G.; Stahl, S. S. J. Am. Chem. Soc. 2006, 128, 7179.
(14) See SI for a more detailed screening of additives.
(15) Unfortunately, aromatic groups at the carbinol position were
not compatible with our reaction conditions, resulting in the oxidation
of the BꢀC bond and leading to the corresponding R-hydroxy ketones as
major byproducts.
(10) (a) Li, J.; Liang, J.-L.; Chan, P. W. H.; Che, C.-M. Tetrahedron
Lett. 2004, 45, 2685. (b) Krasnova, L. B.; Hili, R. M.; Chernoloz, O. V.;
Yudin, A. K. ARKIVOC 2005, 4, 26. (c) Krasnova, L. B.; Yudin, A. K.
Org. Lett. 2006, 8, 2011. (d) Watson, I. D. G.; Yu, L.; Yudin, A. K. Acc.
Chem. Res. 2006, 39, 194.
(11) For related examples on hypervalent iodine-mediated aziridina-
tion processes, see: (a) Richardson, R. D.; Desaize, M.; Wirth, T.
Chem.;Eur. J. 2007, 13, 6745. (b) Fan, R.; Pu, D.; Gan, J.; Wang, B.
Tetrahedron Lett. 2008, 49, 4925. (c) Moriarty, R. M.; Tyagi, S. Org.
Lett. 2010, 12, 364.
Org. Lett., Vol. 13, No. 22, 2011
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