A simple and efficient, Lewis acid catalysed reductive etherification strategy for the stereoselective synthesis of cis‐2,6‐disubstituted morpholines and 1,4‐oxathianes starting from readily available 1,5‐diketones has been developed. The strategy is used in the total synthesis of morpholine‐based natural products (±)‐chelonin A and formal total synthesis of (±)‐chelonin C.

An efficient protocol for the stereoselective synthesis of benzo[1,4]heterocycles via palladium catalyzed Heck reaction on o-halo-aryl-oxa/thia/aza tethered vinylogous carbonates/carbamates/esters has been developed. Unexpected formation of indoles is observed when unprotected 2-iodoaniline tethered vinylogous carbonates are subjected to the Heck reaction. Mechanistic studies indicate that formation of these indoles is an outcome of the interception of the carbopalladation step by nucleopalladation. The method can be used to gain rapid access to the core skeleton of abacopterin A-C.

Stereoselective Synthesis of cis-2,6-Disubstituted Morpholines and 1,4-Oxathianes by Intramolecular Reductive Etherification of 1,5-Diketones. -A triethylsilane/ TmsOTf-mediated reductive etherification is developed to allow the cyclization of diketones of type (I) and (III) to give 2,6-disubstituted morpholines and 1,4-oxathianes in excellent trans-diastereoselectivity. The process is applied to the synthesis of racemic chelonins such as chelonin A (XIII). -(GHARPURE*, S. J.; ANURADHA, D.; PRASAD, J. V. K.; SRINIVASA RAO, P.; Eur. J. Org. Chem. 2015, 1, 86-90, http://dx.