Tetrahedron Letters
A simple and efficient approach to the N-amination of
oxazolidinones using monochloroamine
Uyen Huynh a, Md. Nasir Uddin a, Sarah E. Wengryniuk b,y, Stacey L. McDonald c,y, Don M. Coltart a,
⇑
a Department of Chemistry, University of Houston, Houston, TX 77204-5003, United States
b Department of Chemistry, Temple University, Philadelphia, PA 19122, United States
c Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Chiral nonracemic N-amino cyclic carbamates (ACCs) are important auxiliaries for certain asymmetric
transformations. In the past they have been synthesized from oxazolidinones using methods that require
the preparation and use of non-atom economical aminating agents that can be difficult to prepare, and
often strong bases. In what follows we describe a mild and operationally simple method for the direct
N-amination of oxazolidinones that use NH2Cl derived from commercial bleach.
Received 2 September 2016
Accepted 7 September 2016
Available online 8 September 2016
Keywords:
Amination
Asymmetric
Alkylation
Ó 2016 Elsevier Ltd. All rights reserved.
Chiral nonracemic N-amino cyclic carbamates (ACCs) have
gained attention as auxiliaries for important asymmetric transfor-
mations. The synthetic utility of these systems was first demon-
strated by Friestad in 2000 (Scheme 1a).1 In that work,
hydrazones (5) obtained from the condensation of ACCs and alde-
hydes were found to undergo diastereoselective radical additions
to produce hydrazines (6). Subsequent acylation and then cleavage
of the nitrogen–nitrogen bond furnished the corresponding amines
(7) with excellent overall levels of asymmetric induction. Prior to
these studies, no such methods were available for the direct asym-
metric alkylation of imines via radical methods. Further refinement
of this method by Friestad2 resulted in a manganese-mediated rad-
ical addition procedure that is tolerant of an impressive range of
functional groups and alkyl motifs.3 The latter procedure also
forms the basis of an efficient hybrid radical-ionic annulation
method that enables the highly stereoselective synthesis of pyrro-
lidines and piperidines (cf. Scheme 1b).3 Aldehyde-derived ACC
hydrazones have also been shown to undergo In-promoted allyla-
tion using either an allyl silane4 species or allyl iodide5 as the allyl
source. Asymmetric Mannich-type reactions between aldehyde-
derived ACC hydrazones and a variety of silyl enol ethers also
proceeds with excellent levels of asymmetric induction to give
b-amino carboxylate derivatives.6 Somewhat more recently we
introduced the use of ACC hydrazones as a simple and effective tool
(cf. Scheme 1c).7 In contrast to other asymmetric alkylation meth-
ods,8 these auxiliaries are both easily introduced into and removed
from ketones, with near quantitative recovery. Moreover, deproto-
nation is rapid and alkylation does not require extreme low tem-
perature, yet it proceeds with excellent stereoselectivity and in
excellent yield.
An obvious and straightforward approach to these synthetically
useful ACCs is via the direct N-amination of oxazolidinones.
Oxazolidinones are readily accessible from
a-amino acids using
well-established procedures, and a large number are also commer-
cially available. Consequently, the ability to directly N-aminate
these species would provide rapid access to a range of ACCs.
Indeed, such an approach has been used in the past.9 Unfortunately
the reported methods for the N-amination of oxazolidinones
require the sometimes cumbersome preparation and use of non-
atom economical aminating agents (Fig. 1), and often strong bases.
In what follows, we describe an operationally simple, mild, and
inexpensive procedure for the N-amination of oxazolidinones
using atom economical monochloroamine as the aminating agent,
itself easily derived from commercially available bleach. The
resulting ACCs are obtained in excellent yield.
When we began our studies on the N-amination of oxazolidi-
nones our main objective was to circumvent the use of the non-
atom economical reagents listed in Fig. 1. To do this, we first tried
an indirect approach wherein we would conduct an N-nitrosyla-
tion, followed by a reduction of the nitrosyl group to generate
the N-amino cyclic carbamate (Scheme 2a). To test this idea, we
first attempted the nitrosylation of 17 using nitrous acid,10,11
which produced the desired product (18) in 70%, following silica
for the asymmetric
a-alkylation and a,a-bisalkylation of ketones
⇑
Corresponding author.
Current address.
y
0040-4039/Ó 2016 Elsevier Ltd. All rights reserved.