Enantioselective β-Lactone Formation from Phenyldiazoacetates via Catalytic Intramolecular Carbon-Hydrogen Insertion

Abstract

Dirhodium(II) catalysts with chiral carboxylate or carboxamidate effectively promote b-lactone formation from phenyldiazoacetates in high yield and with up to 63% ee.

Catalytic asymmetric C–H insertion reactions of α-diazocarbonyl compounds

“…Decomposition of 75 in the presence of chiral bis(oxazoline) copper(I) complexes was also shown to be a viable option, although regioselectivities in this case were poor. As previously observed, 127 changing to the phenyl-substituted diazoacetate carbenoid precursor (R = Ph) resulted in exclusive β-lactone production (Table 15, entries e and f). b Reaction conducted in refluxing pentane.…”

“…83,121,122,127 In 2001, Doyle and coworker published a report of enantioselective β-lactone formation from phenyl diazoacetates. 127 Despite the introduction of considerable ring strain via its formation and the deactivating effect of the adjacent electron-withdrawing ester group, successful β-lactone formation was observed from isopropyl and cyclohexyl diazoacetate precursors 71 and 72, respectively [Scheme 7(a) and 7(b)] In both instances, β-lactone formation was the dominant process over competing γ-lactone formation and moderate enantioselectivities were possible in the presence of Rh 2 (S-DOSP) 4 . The phenyl functionality at the α-diazo position of the isopropyl and cyclohexyl substrates is of critical importance in producing the targeted fourmembered ring.…”

Functionalization of Carbon–Hydrogen Bonds Through Transition Metal Carbenoid Insertion

“…In 2001, Doyle and May reported that aryldiazoacetates are quite selective substrates for formation of b-lactones 55 ( Fig. 4) over their five-membered ring counterparts [70]. They examined a number of chiral dirhodium catalysts, and Rh 2 (S-DOSP) 4 (26) in refluxing pentane generally provided the best enantioinduction, with enantioselectivities ranging from 41 to 69% ee.…”

Asymmetric Synthesis through C–H Activation

“…The intramolecular cyclization with cyclohexyl aryldiazoacetate system 57 (Table 4.6 ) preferably formed the β -lactone system 58 when the azetidinone -based dirhodium(II) carboxamidate catalysts were used [119] . The same was also observed with carboxylate catalysts [120] .…”

“…Chemoselectivities were high ( > 97% product selectivity), and the products were formed in 66 -69% yield. However, good control of enantioinduction was not achieved, only 42 -51% ee with the carboxamidate catalysts tested, and 63% ee with Rh 2 ( S -DOSP) 4 [119,168] . The acyclic system 60 only formed γ -lactone product 61 (Table 4.7 ).…”