Oxidation of Amides and P-Lactams

The ruthenium-catalyzed oxidation of l-(methoxycarbonyl)pyrrolidine with t-BuOOH gives 2-(t-butyldioxy)-l-(methoxycarbonyl)pyrrolidine (48) in 60% yield (Eq. (7.63)). 

The tert-butyldioxy amides of the isoquinoline 49 and the indole 50, which are important synthetic intermediates for the synthesis of natural products, were obtained in excellent yields (Eqs. (7.64) and (7.65)). Since the Lewis acid-promoted reactions of these oxidized products with nucleophiles give the corresponding N-acyl-a-substituted amines efficiently, the present reactions provide versatile methods for selective carbon-carbon bond formation at the a-position of amides [115]. 

Typically, the TiC -promoted reaction of a-t-butyldioxypyrrolidine (48) with a silyl enol ether gave the keto amide 51 (81%), while a similar reaction with a less reactive 1,3-diene gave the a-substituted amide 52 (Eq. (7.66)). 

Oxidative modification of peptides has been performed by ruthenium-catalyzed oxidation with peracetic acid. For example, the reaction of N,C-protected peptides containing glycine residues with peracetic acid in the presence of RUCI3 catalyst gives a-ketoamides derived from the selective oxidation at the C position of the glycine residue (81%, conv. 70%) (Eq. (7.67)) [116]. Direct conversion of N-acylproline to N-acylglutamate was achieved by Ru(TMP)Cl2 and 2,6-dichloropyridine N-oxide (Eq. (7.68)) [117]. 

Importantly, (l iJ,3S)-3-[l -(terf-butyldimethylsilyloxy)ethyl]azetidin-2-one (54) can be converted into the corresponding 4-acetoxyazetidinone 55 with extremely high diastereoselectivity (94%, 99%de) (Eq. (7.70)). The product (55) is a versatile and key intermediate for the synthesis of carbapenems of antibiotics. Now, 100 000 kg of the compound 55 is produced per year in the industry. 

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