A Novel Synthetic Route to Chiral γ-Lactams from α-Amino Acids via Rh-Catalyzed Intramolecular C−H Insertion

Abstract

Highly functionalized gamma-lactams are key intermediates for the synthesis of numerous biologically significant natural products. We herein described the synthesis of various chiral gamma-lactams via intramolecular C-H insertion of alpha-diazo-alpha-(phenylsulfonyl)acetamides derived from alpha-amino acids, which possess various functional groups. The cyclizations were highly regio- and stereoselective to afford chiral gamma-lactam motifs in high yields.

Stereo‐ and Regiocontrol in the Formation of Lactams by Rhodium‐Carbenoid C−H Insertion of α‐Diazoacetamides

“…An efficient synthesis of chiral γ-lactams was developed using α-diazo-α-(phenylsulfonyl)acetamides derived from α-amino acids. [46] As shown in Scheme 37 the precursor 108 was prepared by a ringclosure reaction with 2,2-dimethoxypropane. The regioand stereochemical outcomes of the cyclisation were attributed to conformational preferences resulting from the presence of the gem-dimethyl group.…”

Chemistry of Unprotected Amino Acids in Aqueous Solution: Direct Bromination of Aromatic Amino Acids with Bromoisocyanuric Acid Sodium Salt under Strong Acidic Condition

“…However, only a few studies [1][2][3][4][5][6][7][8][9][10][11] of synthetic reactions using unprotected (free) amino acids have been reported. Most of the synthetic transformations to natural products, pharmaceuticals, and chiral auxiliaries have been performed [12][13][14][15] with protected amino acids to increase solubility in organic solvents and avoid side reactions. We have reported 16,17) a three-step synthesis of optically active clavicipitic acids (6), ergot alkaloids, from 4-bromoindole (1) and dl-serine (2) that involved a reaction of unprotected amino acids in aqueous media as a key step (Chart 1).…”

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

“…Intramolecular C–H insertion of diazo compound 12 yielded the desired trans ‐γ‐lactam 13 in 85 % yield with exclusive regio‐ and stereoselectivities. The configuration of the two newly generated stereocenters at C(6) and C(7) of the γ‐lactam 13 was unambiguously elucidated and discussed in our previous report 5b…”