CATALYTIC ASYMMETRIC-SYNTHESIS OF POLYCYCLIC COMPOUNDS BY ASYMMETRIC HECK REACTION

In 1989, we succeeded in demonstrating the first example of an asymmetric Heck reaction. Treatment of the prochiral alkenyl iodide 4 b with Cl2Pd(R)-BINAP (10 mol%), Ag3PO4 (2 molar equiv) and CaCO3 (2.2 molar equiv) in 1-methyl-2-pyrrolidinone produced the cis-decalin derivative 8 b with 80% ee. The result suggested that the presence of a silver salt produced the Pd+ intermediate 11 with 16-electron configuration by abstraction of I- to result in the formation of 8 b with high ee. Under the similar conditions, the cis-decalin derivative 18 of 92% ee and the cis-hydrindan derivative 26 a of 86% ee were obtained from the corresponding alkenyl iodides, respectively. On the other hand, it was found that treatment of the prochiral alkenyl triflate 19 d with Pd(OAc)2 (5 mol%). (R)-BINAP (10 mol%) and K2CO3(2 molar equiv) in toluene gave 8 d in 91% ee. Furthermore, 27 was cyclized to 26 b in 73% ee under the similar conditions, which was successfully transformed into the key intermediate 34 for oppositol. An asymmetric Heck reaction was also useful for the synthesis of polycyclopentanoids. Thus, the prochiral alkenyl triflate 59 was treated with 1.7 mol% of Pd(OAc)2, 2.1 mol% of (S)-BINAP and 1.7 equiv of tetrabutylammonium acetate in DMSO afforded the cyclopentanoid 60 of 80% ee in 89% yield. The reaction was found to be useful as well for the capture by a C-centered nucleophile instead of tetrabutylammonium acetate. giving 68 c of 80% ee in one-step from 59. The cyclopentanoid 60 was converted to 43 in a seven-step process, which is a key synthetic intermediate for capnellenols.