a similar strategy for secondary alcohols.7 We have also
reported the determination of absolute configuration of
primary amines using proto and deutero chiral acylating
reagents and mass spectrometry.8
thiazolidine-2-thione required shorter reaction times,
decreased temperatures, and in some cases, decreased
reaction concentration. In all cases, the presence of an
Table 1. Identification of Fast-Reacting Catalyst for
Enantiopure Oxazolidinones
Scheme 1. Parallel Acylation Reactions Were Used To Identify
the Fast-Reacting Catalyst for Each Substrate
Herein, we describe our results with chiral R-substituted
oxazolidinones, lactams, and thiolactams. This class of
molecules has found widespread use in stereoselective
chemical transformations,9 natural product synthesis,10,11
and pharmaceutical targets.12 Birman has reported the
resolution of some oxazolidinones and lactams using dif-
ferent catalysts that were more capable for each class.13 We
prefer Birman’s HBTM catalysts,14 which are less selective
but can be applied to a wider variety of substrates with
adequate and predictable selectivity. The HBTM catalyst
allows a single catalyst to be used in the determination of
absolute configuration for a variety of substrate classes.7
The reaction conditions vary based on the class of
substrates under consideration. The observed reactivity
trend is consistent with the acidity of the nitrogen proton.
As acidity increases, reactivity increases. Most oxazolidi-
nones provided sufficient conversion at 3 h and 50 °C.
Lactams showed the greatest variability with the reactivity
decreasing with increased ring size. Simple β-lactams
showed reactivity comparable to the oxazolidinone
cases. The γ- and δ-lactams were the least reactive sub-
strates requiring longer reaction times and increased cat-
alyst loading. The thiolactams, oxazolidine-2-thione, and
(7) Wagner, A. J.; David, J. G.; Rychnovsky, S. D. Org. Lett. 2011,
13, 4470–4473.
(8) Miller, S. M.; Samame, R. A.; Rychnovsky, S. D. J. Am. Chem.
Soc. 2012, 134, 20318–20321.
(9) Zappia, G.; Cancelliere, G.; Gacs-Baitz, E.; Delle Monache, G.;
Misiti, D.; Nevola, L.; Botta, B. Curr. Org. Chem. 2007, 4, 238–307.
(10) Babu, K.; Reddy, R.; Rao, S.; Palnati, V.; Gutta, M. Synth.
Commun. 2012, 42, 2624–2631.
(11) (a) Takao, K.; Aoki, S.; Tadano, K. J. Synth. Org. Chem., Jpn.
2007, 65, 460–469 and references therein. (b) Zappia, G.; menendez, P.;
Delle Giuliano, M.; Mesiti, D.; Nevola, L.; Botta, B. Mini-Rev. Med.
Chem. 2007, 7, 389–409. (c) Gulder, T. A. M.; Moore, B. S. Angew.
Chem., Int. Ed. 2010, 49, 9346–9367.
(12) Konaklieva, M. I.; Plotkin, B. J. Curr. Med. Chem.: Anti-Infect.
Agents 2003, 2, 287–302.
(13) (a) Yang, X.; Bumbu, V. D.; Liu, P.; Li, X.; Jiang, H.; Uffman,
E. W.; Guo, L.; Zhang, W.; Jiang, X.; Houk, K. N.; Birman, V. B. J. Am.
Chem. Soc. 2012, 134, 17605–17612. (b) Fowler, B. S.; Mikochik, P. J.;
Miller, S. J. J. Am. Chem. Soc. 2010, 132, 2870–2871.
(14) Birman, V. B.; Li, X. Org. Lett. 2008, 10, 1115–1118.
a All conversions are averages of triplicate runs unless otherwise
stated. b % conversion at 1 h: (S) = 12, (R) = 21. c Average of duplicate
runs are reported. d 10 mol % catalyst loading. e Reaction mixture
diluted 5-fold from the standard conditions. f Standard deviation range
for % conversion: (S) = 0 À 2.8, (R) = 0.6À2.9. Details are provided in
the Supporting Information.
B
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