Synthesis of cystothiazole E and formal syntheses of cystothiazoles A and C by Pd0-catalyzed cross-coupling reactions.
The synthesis of the naturally occurring bithiazole (+)-cystothiazole E (1e) 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 (1e). In addition, aldehyde 21 was transformed into aldol product 22 (72%) which has been used in previous syntheses of cystothiazole A (1a) and C (1c). In this respect, the preparation of compound 21 represents a formal total synthesis of these cystothiazoles.
Bach
Thorsten
T
Lehrstuhl für Organische Chemie I Technische Universität München, Lichtenbergstrasse 4 85747 Garching, Germany. thorsten.bach@ch.tum.de
Heuser
Stefan
S