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Asymmetric Aldol Reaction of Thiazole‐Carbaldehydes: Regio‐ and Stereoselective Synthesis of Tubuvalin Analogues
Author(s) -
Paladhi Sushovan,
Das Joydeb,
Samanta Mousumi,
Dash Jyotirmayee
Publication year - 2014
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201400640
Subject(s) - aldol reaction , chemistry , thiazole , enantioselective synthesis , stereoselectivity , ketone , yield (engineering) , amination , combinatorial chemistry , isopropyl , catalysis , organic chemistry , stereochemistry , materials science , metallurgy
The first organocatalytic enantioselective approach to precursors of tubuvaline (pre‐Tuv) is presented employing a prolinamide‐catalyzed aldol reaction of easily accessible thiazole‐carbaldehyde with methyl isopropyl ketone “on water” in excellent yield as well as regio‐ and enantioselectivities. The analogues of pre‐Tuv were achieved using an L ‐proline‐catalyzed direct asymmetric aldol reaction of substituted thiazole‐carbaldehydes with acetone. A direct and flexible approach to the tubavaline (Tuv) core of tubusylins has been established employing the reductive amination of the pre‐Tuv species. The key aldol reaction should greatly expand the potential of this strategy to the synthesis of natural product tubulysins and a range of analogues.