1195973-76-2

Upstream product

• 440677-00-9 3-methylene-2-oxo-piperidine-1-carboxylic acid benzyl ester 
• 264921-02-0 tert-butyl-dimethyl-(2-methyl-1-methylene-hex-2-en-4-ynyloxy)-silane 
• 98-59-9 p-toluenesulfonyl chloride 
• 68074-14-6 3-methylidene-2-oxo-piperidine 
• 870290-88-3 (6S,7S)-9-(tert-Butyl-dimethyl-silanyloxy)-8-methyl-7-prop-1-ynyl-2-(toluene-4-sulfonyl)-2-aza-spiro[5.5]undec-8-en-1-one 
• 870290-79-2 (6S,7S)-9-(tert-Butyl-dimethyl-silanyloxy)-8-methyl-1-oxo-7-prop-1-ynyl-2-aza-spiro[5.5]undec-8-ene-2-carboxylic acid benzyl ester 
• 870290-81-6 (6S,7S)-9-(tert-Butyl-dimethyl-silanyloxy)-8-methyl-7-prop-1-ynyl-2-aza-spiro[5.5]undec-8-en-1-one 

Relevant academic research and scientific papers

Total synthesis of the spirocyclic imine marine toxin (-)-gymnodimine and an unnatural C4-epimer

The first total synthesis of the marine toxin (-)-gymnodimine (1) has been accomplished in a convergent manner. A highly diastereo- and enantioselective exo-Diels-Alder reaction catalyzed by a bis-oxazoline Cu(II) catalyst enabled rapid assembly of the spirocyclic core of gymnodimine. The preparation of the tetrahydrofuran fragment utilized a chiral auxiliary based anti-aldol reaction. Two major fragments, spirolactam 56 and tetrahydrofuran 55, were then coupled through an efficient Nozaki-Hiyama-Kishi reaction. An unconventional, ambient temperature t-BuLi-initiated intramolecular Barbier reaction of alkyl iodide 64 was employed to form the macrocycle. A late stage vinylogous Mukaiyama aldol addition of a silyloxyfuran to a complex cyclohexanone 83 appended the butenolide, and a few additional steps provided (-)-gymnodimine (1). A diastereomer of the natural product was also synthesized, C4-epi-gymnodimine (90), derived from the vinylogous Mukaiyama aldol addition.