Total Synthesis and Absolute Stereochemical Assignment of (+)- and (−)-Galbulimima Alkaloid 13

Abstract

We describe the total synthesis of (+)- and (-)-galbulimima alkaloid 13. The absolute stereochemistry of natural (-)-galbulimima alkaloid 13 is revised to 2S. Sequential use of catalytic cross-coupling and cross-metathesis reactions followed by an intramolecular Diels-Alder reaction provided the required trans-decalin AB-ring system and masked the C16 carbonyl as an N-vinyl carbamate for late-stage unveiling in the form of the necessary C16 enone. A vinyl radical cyclization secured the C-ring, while successful execution of our strategy for introduction of the CDE-ring system in complex galbulimima alkaloids provided the target pentacycle with complete diastereoselection.

Stereoselective Intermolecular Formal [3+3] Cycloaddition Reaction of Cyclic Enamines and Enones

“…[5] Motivated by the efficiency of the transient-d-imino ketone strategy that we employed [6] for the introduction of the CDE ring system of class II and class III galbulimima alkaloids [7] (Scheme 2), we sought to develop a new formal [3+3] cycloaddition reaction.…”

“…The stereoselective formation of tricycles 11 a-c via the corresponding imino ketones 7 a-c is consistent with our proposed biogenesis of this substructure in the galbulimima alkaloids. [6] The use of iminium chloride 5 b [9] Scheme 1. Formal [3+3] cycloaddition reaction.…”

Mild and Highly Efficient Copper(I) Inspired Acylation of Alcohols and Polyols

“…Sharpless et al as well as the Meldal research group independently employed the use of copper(I) catalysis in the formation of a cyclic adduct during azide-alkyne cycloaddition reactions [33,34]. In the synthesis of (−)-galbulimima alkaloid, the Movassaghi research group reported the use of copper-inspired coupling of vinyl bromide and oxazolidinone as one of its key intermediate steps [35]. A similar strategy was also employed in the synthesis of himandrine alkaloid [36].…”

Microwave Assisted N-Alkenyl Condensation between Pyrrolidine-2-thione and Various Aldehydes

“…After completion of the reaction, the mixture was allowed to cool at the room temperature, and the crude product was extracted into CH 2 Cl 2 . The removal of the solvent using rotary evaporator under reduced pressure and flash column chromatography using CH 2 …”

“…N-Vinyl analogues are widely used as very important intermediates in polymerizations, 1 alkaloid syntheses, 2 protecting procedure 3 , Diels-Alder reactions 4 , regioselective Heck couplings 5 and pyrimidine syntheses. 6 Whereas numerous reaction methods for the preparation of N-vinyl analogues have been previously reported using dehydration, 7 dehydroalkoxylation, 8 copper 9 and palladium 10 catalyzed vinylation, coupling with 2-halo vinyliodides, 11 and decomposition of acyloxy ethyl derivatives, 12 introducing vinyl moieties at the nitrogen atom in lactams have not been generally studied.…”