1. Structural elucidation of triquinane natural products via total syntheses 2. Studies on the tandem cyclization of 1,3-diyls generated from the desilylation of silyl vinyl iodides

Abstract

Alkylidene carbene, a reaction intermediate that drew synthetic chemists’ interest, is known to undergo synthetically useful chemical transformations such as 1,2-migration and 1,5 C-H insertion. However, generation of Trimethylenemethane (TMM) diyl, which is equally intriguing as the other reactions, was underexplored. Pioneering works by Lee group developed several TMM diyl-mediated tandem cyclization methods by preparing alkylidene carbene from various sources. However, their methods were limited by either strongly basic or pyrolytic conditions. In order to solve this problem, we explored a novel, mild generation method for alkylidene carbene species by utilizing silyl vinyl iodides and tetramethyl ammonium (TMAF). Through this study, we also discovered an unprecedented mechanistic insight that cyclopropanation reaction of alkylidene carbene with olefin is actually reversible under ambient temperature. Angular triquinane, a family of sesquiterpene natural products, is known for its angularly fused tricyclic structure. While many members of the family such as isocomene and pentalenene were thoroughly synthesized and studied by the chemical society, the actual structures of the several members of the family are still ambiguous. In this study, we attempted to synthesize three members of such angular triquinanes and verify their structures. Pethybrene was a new sesquiterpene hydrocarbon that was isolated by Kőnig from the essential oil of rhizomes of Petasites hybridus in 2002. While König assigned the natural product’s angularly fused structure via NMR studies, the following computational study by Kutateladze and Kuznetsov in 2017 proposed a completely different hydrocarbon bearing 6-5-5 tricyclic scaffold. In this study, we achieved total synthesis of both putative and revised structures by utilizing pauson-khand reaction and Pirrung’s previously reported synthetic pathway of isocomene. By comparing the 13C-NMR chemical shifts of both structures, it was concluded that pethybrene was actually the revised structure of 6-5-5 tricyclic hydrocarbon. Silphinene was isolated from silphinum perfoliatum by Bohlmann and Jakupovic in 1980. Its angularly fused triquinane structure was originally assigned via 1H NMR Spectroscopy of the original compound and those of oxidized products. While several total syntheses of the natural product were already achieved, none of the report was asymmetric. In order to verify its absolute chemistry, several synthetic pathways utilizing TMM diyl-mediated tandem cyclization as a key step was investigated. Schizandene, a new sesquiterpene hydrocarbon bearing an angularly fused triquinane, was reported in 2015. schizandene was reported. While its one-dimensional NMR spectroscopy clearly implied that the natural product was a single stereoisomer, the stereochemistry of the methyl group remains undetermined. In order to verify its structure, we designed a divergent synthetic pathway for both diastereomers.