Stereocontrolled synthesis of some novel functionalized heterocyclic amino ester and amide derivatives with multiple stereocenters

Abstract

The synthesis of functionalized fused-ring β-amino lactones and lactams with multiple stereocenters has been accomplished from readily available strained bicyclic β-amino acids via stereocontrolled RRM transformations.

Application of Metathesis Protocols to the Stereocontrolled Synthesis of some Functionalized β‐Amino Esters and Azaheterocycles

“…When amide (�)-179 was subjected to metathesis, it behaved in the same way as its ester analogue (�)-177 (Scheme 32). [107] Substrates ester (�)-182 and amide (�)-184 were synthesized from N-Boc protected diendo amino acid (�)-181 [106] . When they were subjected to olefin metathesis, ROM took place instead of RRM.…”

“…Attempts to trigger ring-closing metathesis by treatment of isolated (�)-183 and (�)-185 with metathesis catalysts in the absence of ethylene failed (Scheme 33). [107] Diexo β-amino ester (�)-186 was prepared by Opropargylation of compound (�)-176, and then it was subjected to olefin metathesis. With second generation catalysts, the only product was cispentacin derivative (�)-187, which was formed via ROM.…”

“…Two products were formed: the ROM/RCEYM product (�)-192 (this was the major product with first generation catalysts) and ). [107] Diendo compounds: β-amino ester (�)-193 and β-amino amide (�)-197 were synthesized from N-protected diendo βamino acid (�)-181. When subjected to olefin metathesis, ester (�)-193 behaved in the same way as its diexo analogue (�)-186: first generation catalysts furnished a three-component mixture (in decreasing order of yields: ROM/CEYM compound (�)-195, ROM compound (�)-194, and the desired RRM product (�)-196), while second generation catalysts gave ROM compound (�)-194 as sole product.…”

“…Metathesis of amide (�)-197, however, was slightly different than metathesis of its stereoisomer (�)-190: all four catalysts provided a three-component mixture (in decreasing order of yields: ROM product (�)-198, ROM/CEYM product (�)-199, and the desired RRM product (�)-200) (Scheme 35). [107]…”

“…Even treatment of isolated ROM products (�)-214 and (�)-216 with metathesis catalysts in the absence of ethylene was unsuccessful in triggering RCM (Scheme 38). [107] After reaching the target products by ROM/RCM failed, we switched to ROM/RCEYM. Thus, oxanorbornene derivatives (�)-217 (a propargyl ester) and (�)-220 (an Npropargylated amide) were synthesized and treated with metathesis catalysts under ethylene atmosphere.…”