Rhodium‐Catalyzed Asymmetric Cycloisomerization of 1,3‐Diketones with Keto‐Vinylidenecyclopropanes: Synthesis of Enantiomerically Enriched Cyclic β‐Amino Alcohols

Abstract

We report here an effective and atom‐economical method to synthesize enantiomerically enriched cyclic β‐amino alcohols via a rhodium‐catalyzed asymmetric cycloisomerization of 1,3‐diketones with keto‐vinylidenecyclopropanes. The reactions proceed through a Rh‐catalyzed transformation of keto‐vinylidenecyclopropanes via cleavage of the distal C−C bond of the three‐membered ring as a three‐carbon synthon, allowing the generation of a range of enantiomerically enriched cyclic β‐amino alcohols tethered to an alkene and an 1,3‐dione moiety in good yields with high ee values under mild conditions. Derivatizations including allylation of the functionalized β‐amino alcohols and subsequent RCM reaction as well as the preparation of a pyrazole derivative were carried out as well.

Highlighting the Rich Chemistry of the Allenone Moiety

“…[214] Keto-vinylidenecyclopropanes 119 a have been devised as precursors of cyclic aminoalcohols 470 through a transition metal catalyzed annulation process involving the allenone moiety (Scheme 80a). [215] An initial rhodium-catalyzed oxidative addition to allenic systems 119 a with concomitant ring opening of the cyclopropane nucleus has resulted in complexes 471, which is followed by a carbometallation process providing the piperidine ring in intermediates 472. The organometallic intermediate 472 is eventually trapped with a nucleophile such as 1,3-dicarbonyl compounds 469, generating alkoxy-metal compounds 473, which can afford aminoalcohols 470 after protonolysis.…”

“…Chiral phosphine (R)-TolBINAP provided enantiomeric excesses of up to 99% in final piperidine containing systems 470 (Scheme 80a). [215] In a similar approach, a synergistic Rh/Ag catalyzed process has been found to be efficient for the synthesis of aminoalcohols 475 from vinylidenecyclopropanes 119 b and poor nucleophiles such as terminal alkynes 474 (Scheme 80b). [216] As mentioned before, initial oxidative addition and carbometallation lead to intermediates 472, which undergo transmetallation with silver acetylides Ag-474, products of the reaction of terminal alkynes 474 with AgNTf 2 , forming complexes 476.…”

“…The organometallic intermediate 472 is eventually trapped with a nucleophile such as 1,3‐dicarbonyl compounds 469 , generating alkoxy‐metal compounds 473 , which can afford aminoalcohols 470 after protonolysis. Chiral phosphine ( R)‐ TolBINAP provided enantiomeric excesses of up to 99% in final piperidine containing systems 470 (Scheme 80a) [215] . In a similar approach, a synergistic Rh/Ag catalyzed process has been found to be efficient for the synthesis of aminoalcohols 475 from vinylidenecyclopropanes 119 b and poor nucleophiles such as terminal alkynes 474 (Scheme 80b) [216] .…”