Formal Asymmetric Synthesis of (-)-Detoxinine
SCHEME 1. Typical Approaches to N-Containing Cyclic
Compounds Having a Vicinal Amino Diol Substructure
mentary and highly diastereoselective methods, which allow for
control of the two newly formed stereocenters with either trans
or cis stereoselectivity at the 2-pyrrolidinone ring (B). In
addition, a formal asymmetric synthesis of (-)-detoxinine is
disclosed.
Results and Discussion
Recently, we have reported an approach to scaffold B by
epoxidation of enamides14 E with m-chloroperbenzoic acid
(MCPBA) followed by reductive dehydroxylation.15 This method
shows high trans diastereoselectivities at the pyrrolidine ring
but only 1:1 to 1:4 threo/erythro diastereoselectivities at the
exocyclic chiral center. Taking into account that the exo-
diastereoselectivity in the transformation of 7 to 9 is determined
in the epoxidation step, and to improve the stereoselectivity at
the C1′ position, we investigated the use of oxidants other than
MCPBA.15 A search of literature revealed that a number of
oxidation systems have been used to functionalize the enamides,
which include dimethyldioxirane (DMDO),15a,b,e,f,16 Oxone,17
OsO4/N-methylmorpholine-N-oxide,18 microencapsulated OsO4/
NMO,15c K2OsO4‚2H2O/K3Fe(CN)6,15c Jacobsen epoxidation,19
Sharpless dihydroxylation,15a,19 PhIO/MnO,15a (S,S)-(salen)MnIII-
Cl,15a and anodic oxidation conditions,20 etc. Considering the
environmental, economical, safety, and practice factors, Oxone
(2KHSO5 + KHSO4 + K2SO4, potassium peroxomonosulphate),
an oxidant that is stable and commercially available in large
quantities, was selected for our investigation. Thus, treatment
of a methanolic solution of 7d (7, R ) i-Pr) with Oxone resulted
in, after reductive demethoxylation (F3B‚OEt2, Et3SiH, CH2-
2-formyl pyrrolidines5b,c,12 C (Scheme 1, path A) and the
reaction of pyrrolidine R-carbanions13 of type D (Scheme 1,
path B) with aldehydes represent two typical ones. Recently,
we reported the third flexible approach to the building blocks
with generic structure B, which relies on the epoxidation-
reduction of the enamides14 E. The major drawback of the
reported approaches is two-fold, namely, poor stereoselectivity
at the newly formed exocyclic chiral center5b,c,12-14 and the
limitation to only one, generally, trans diastereomer.5b,c,12-14
In continuation of our work on the asymmetric synthesis of the
scaffold A-containing alkaloids,12,13 we now report two comple-
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