29(C-5) 水銀トリフラートを開発して挑んだステロイド生合成の謎(口頭発表の部)

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In 1983, we developed an olefin cyclization agent, mercuric triflate, Hg(OTf)_2, and offered the first experimental evidence that the olefin cyclization takes place by a stepwise mechanism via conformationally flexible cationic intermediates by trapping intermediates 8, 9, and 10 to give tert-alcohols 5, 6, and 7, respectively, during the cyclization of geranylgeranyl acetate (4) in the presence of water. Now we have focused on the C-ring problem of sterol biosynthesis that includes rearrangement from the more stable tert-cation 15 to a less stable six-membered ring secondary cation 16. We have achieved a model study using diol 18 and investigated the fate of the corresponding tert-cation 19 generated by the reaction with Lewis acids. The cation generated with BF_3・Et_2O, SnCl_4, Sc(OTf)_3, FeCl_3, TiF_4 and CF_3SO_3H underwent a hydride shift to generate tert-cation 20 and afforded spiro-cyclic 21 as the sole product. On the other hand, TiCl_4 selectively induced rearrangement into the six-membered ring secondary cation 22 and afforded 23 and related six-membered ring products. CONFLEX-MOPAC calculation elucidated the existence of two conformers 24 and 25, for the naked cation of 19. Parallel (the five-membered ring and the cationic plane) conformer 24 is favorable for the hydride shift to form 20 and the perpendicular 25 should lead to C-C bond migration to form 22. The ab initio calculation of the conformation of cations in the presence of the counteranion showed that [TiCl_4,OH] significantly destabilizes parallel cation 24 and should lead to six-membered ring secondary cation 22. On the other hand, counteranions [TiF_4OH] and [BF_3OH] destabilize six-membered ring secondary cation 22, and a hydride shift into 20 should be the dominant pass. We surmise that the control of cation conformation (parallel or perpendicular) by the carboxylates of glutamic and aspartic acids to act as counteranion in an enzymatic cavity is a distinct possibility. Therefore, this result is the first example that overcame the big Markovnikov wall experimentally and theoretically at least to our knowledge. We have also investigated Hg(OTf)_2-catalyzed hydration of alkyne affording methyl ketone 36, 38, and 40, Hg(OTf)_2-catalyzed hydroxylative enyne cyclization to give 47, and Hg(OTf)_2-(TMU)_3 catalyzed arylyne cyclization leading to 50 and 51 with highly efficient catalytic turnover. Protodemercuration by in-situ generated TfOH of vinyl mercuric intermediates 42, 46, and 54 should be the key step that regenerates the catalyst Hg(OTf)_2.
天然有機化合物討論会の論文
2004-10-01

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