N–H insertion reactions of rhodium carbenoids. Part 1. Preparation of α-amino acid and α-aminophosphonic acid derivatives

N-H Insertion reactions of rhodium carbenoids. Part 4. New chiral dirhodium(II) carboxylate catalysts

“…Benzyl carbamate was selected as the N-H component since it is known to give high yields of N-H insertion products with achiral dirhodium(II) catalysts. 2 In the event, decomposition of methyl 2-diazophenylacetate, 1, in the presence of the 16 chiral dirhodium(II) catalysts gave the expected N-benzyloxycarbonylphenylglycine methyl ester 22 in good yield (62-92%). However, the enantiomeric excess (ee), as determined by HPLC on a chiral stationary phase, was less than 5% in all cases (Table 1).…”

“…7 However, the possibility that such N-H insertion reactions could be carried out stereoselectively to give α-amino acid derivatives as single enantiomers at the new stereocentre remains the most attractive aspect. Attempts to use chiral auxiliaries (Scheme 1, R 2 = chiral group) resulted in modest asymmetric induction, 2,8 and little work on the use of chiral catalysts has been reported. Thus McKervey's group reported that intramolecular N-H insertion reactions could be carried out using dirhodium(II) mandelate as catalyst to give the desired piperidine product in 53% yield with 45% ee (Scheme 3).…”

“…In previous papers, 2,3 we have reported that diazoesters react with a range of R 3 NH 2 compounds in the presence of dirhodium(II) catalysts to give α-amino acid derivatives, the products of N-H insertion of the intermediate rhodium carbene, in high yield (Scheme 1). …”

Dirhodium(II) Carbenes : The Chiral Product Cascade

“…To date the N-H insertion reactions reported have shown disappointing levels of asymmetric induction (< 50% ee), and much more research is required before this becomes a useful synthetic tool (Aller et al, 1996;Garcia et al, 1996). On the other hand, Si-H insertion has shown greater promise.…”

Late-stage C–H functionalization of complex alkaloids and drug molecules via intermolecular rhodium-carbenoid insertion

“…Alkaloids represent an extremely challenging class of natural products for direct C-H functionalization, because they typically contain a basic amine and a variety of other reactive functionality. In particular, a basic amine can impede many C-H-activation methodologies, as the nitrogen functionality may coordinate to and poison the catalyst [24][25][26] or generate undesirable side reactions 27,28 . Only a few examples of selective oxidation 29,30 or C-H amination of alkaloid derivatives have been reported, although in the case of the latter aza-ylide products are also formed and in many cases are the exclusive product 27 .…”