Total Synthesis of (−)-Cylindricine C

Abstract

(−)-Cylindricine C has been synthesized from commercially available (S)-(−)-1,2,4-butanetriol in 11 steps with an overall yield of 12%. The key step utilizes a CrCl2 reduction of an azide to form the corresponding amine with a subsequent double Michael addition to create the tricyclic skeleton of cylindricine from a monocyclic substrate.

Chemoselectivity and the Curious Reactivity Preferences of Functional Groups

“…Clearly, steric effects alone were not sufficient for predicting the chemoselectivity of the cyclization, thus highlighting the necessity for considering electronic effects as well. An aldol/dehydration sequence followed by double conjugate addition pioneered by Molander and Ronn, [176] and cleavage of the TBDPS group completed the synthesis of (+)-cyclindricine C.…”

Studies on Total Synthesis of the Cylindricine/Fasicularin/Lepadiformine Family of Tricyclic Marine Alkaloids

“…13 Starting with the known 14 (S)-1,2,4-butanetriol-derived tosylate 35 as the source of absolute chirality, the lithium anion of the N,N-dimethylhydrazone derivative of cyclohexanone could be alkylated to form ketone 36 (Scheme 6). This ketone was then transformed as shown in three steps to dienone 37.…”

Cross‐Coupling Reactions to sp Carbon Atoms

“…The (Zalkynylhaloalkenes 14 can be synthesized in relatively good yields from 1-alkynes in a regio-and stereo-selective manner, following haloboration with Br-9-BBN and subsequent treatment with alkynyllithium and iodine [Eq. (7)] [13]. …”

“…With Pd-catalysts, alkynyl groups are more readily transferred than alkyl groups to the aryl to vinyl iodide to afford sp-sp' carbon bonds [Eqs. ( 13). …”