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Parallel Kinetic Resolution of N-Heterocycles by N-Acylations in Flow
Flow Chemistry and Polymer-Supported Pseudoenantiomeric Acylating Agents Enable Parallel Kinetic Resolution of Chiral Saturated N-Heterocycles.
Nat. Chem. 2017;
18 July 2017 (online)
Key wordsflow chemistry - acylation - N-heterocycles - parallel kinetic resolution - polymer-supported reagents
A flow system for parallel kinetic resolution of N-heterocycles by using polymer-supported pseudoenantiomeric acylating agents was developed. A racemic mixture of heterocycles 1 was converted into the corresponding enantioenriched amides 4 and 5 in 17–50% yield by using a flow-reaction system with acylating agents 2 and 3 (0.5 mol equiv each).
The resulting amides 4 and 5 were readily deprotected to give the corresponding free amines. Thus, for example, (R,S)- and (S,R)-mefloquine (1e) were obtained from a 1:1 mixture of amides 4e and 5e by selective deprotection without detectable epimerization (60–90% yield).