Stereogenic Evolution of clasto‐Lactacystin β‐Lactone from L‐Serine

Abstract

Reported herein is a novel synthesis of clasto‐lactacystin β‐lactone. The γ‐lactam core was selectively prepared by an intramolecular C–H insertion to establish the stereocenter, C(6). The ensuing construction of the quaternary C(5) and carbinol C(9) centers was facilitated by aldol with excellent stereoselection. All these new stereochemistries were induced by the inherent chirality of L‐serine without employing chiral auxiliaries or reagents. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Total Syntheses of (−)-α-Kainic Acid and (+)-α-Allokainic Acid via Stereoselective C−H Insertion and Efficient 3,4-Stereocontrol

“…Intramolecular C−H insertion of diazo compound 19 then gave the desired trans-γ-lactam 20 as a single isomer in 92% yield with excellent regio- and stereoselectivities. The configuration of the two newly generated stereocenters, C-6 and C-7 of γ-lactam 20 was unambiguously elucidated and discussed briefly in our previous reports 3 Synthesis of γ-Lactam 20 via C−H Insertion …”

“…First, the acetylation of the phenylsulfone was carried out efficiently, giving 21 as a white solid under the optimized conditions utilizing Ac 2 O and NaH in THF solution (Scheme ). The reaction was regio- and stereoselective, offering only one diastereomer while the new stereochemistry was assigned on the basis of the previous similar examples 13d. Next, attention was paid to the vinylation of the carbonyl group in acetyl compound 21 .…”

“…Over the recent years, the Rh(II)-catalyzed intramolecular C−H insertion reaction has emerged as a prevailing strategy for the construction of numerous cyclic compounds including β-, γ-lactams . We also reported an efficient methodology to synthesize chiral γ-lactams from α-amino acids via stereoselective C−H insertion . Utilizing this protocol, the γ-lactam 6 could be prepared from ( l )-glutamic acid ( 8 ), securing the pyrrolidine core of kainoids.…”