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Synthesis of Cystothiazole E and Formal Syntheses of Cystothiazoles A and C by Pd 0 ‐Catalyzed Cross‐Coupling Reactions
Author(s) -
Bach Thorsten,
Heuser Stefan
Publication year - 2002
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20021216)8:24<5585::aid-chem5585>3.0.co;2-1
Subject(s) - stille reaction , stannane , alkyne , yield (engineering) , aldehyde , coupling reaction , total synthesis , stereochemistry , aldol reaction , chemistry , heck reaction , combinatorial chemistry , palladium , organic chemistry , catalysis , physics , thermodynamics
Abstract The synthesis of the naturally occurring bithiazole (+)‐cystothiazole E ( 1 e ) is described starting from oxazolidinone 2 . It proceeded in 10 steps and an overall yield of 37 %. The key reaction of the sequence was a Suzuki cross‐coupling between bromobithiazole 4 and the ( E )‐alkenylboronic acid derived from alkyne 18 (94 % yield). Prior to the synthesis, more general investigations related to the cross‐coupling of bromobithiazole 4 were undertaken. Whereas Heck reactions failed Suzuki and Stille cross‐coupling reactions were successfully conducted. By this means, the alkenylboronic acid derived from alkyne 11 and stannane 12 could be transformed into the corresponding alkenylbithiazoles 13 (92 %) and 14 (52 %). The Stille cross‐coupling of compound 4 and stannane 5 allowed access to aldehyde 21 (97 % yield) and paved the way for an alternative route to (+)‐cystothiazole E ( 1 e ). In addition, aldehyde 21 was transformed into aldol product 22 (72 %) which has been used in previous syntheses of cystothiazole A ( 1 a ) and C ( 1 c ). In this respect, the preparation of compound 21 represents a formal total synthesis of these cystothiazoles.