Macrocyclic Cyclopropenes by Highly Enantioselective Intramolecular Addition of Metal Carbenes to Alkynes

Abstract

The intramolecular addition of a diazo ester group to a triple bond in the presence of chiral dirhodium(II) carboxamidate catalysts gives macrocyclic lactones with a fused cycloproprene ring [Eq. (a)]. This efficient reaction is characterized by high enantiocontrol (up to 98% ee) and chemoselectivity.

Macrocycle Formation from Catalytic Metal Carbene Transformations

“…Particularly noteworthy is the outcome from reaction of the propargyl system linked to the diazoacetate through a cis-2-buten-1,4-diyl linker (Scheme 9). 22 Allylic cyclopropanation occurs to the virtual exclusion of macrocyclic cyclopropenation with Rh 2 (5S-MEPY) 4 , whereas this latter transformation is dominant with Rh 2 (4S-IBAZ) 4 , and CuPF 6 /LH gives mixed results.…”

“…19,22 Here chiral rhodium(II) carboxamidates, especially Rh 2 (4S-IBAZ) 4 , are even more selective than CuPF 6 /LH. Several examples are provided that confirm the viability of these reactions (Scheme 8).…”

Cyclopropanation

“…A rearrangement to vinyl carbenes and then formation of bicyclic or tricyclic products via tandem reactions were observed. Only for more flexible compounds , isolation of polycyclic cyclopropenes was feasible (Scheme 40) (136). Apart from cyclopropenation, catalytic aziridination with nitrene transfer to olefins is generally considered an analogue reaction of metal-catalyzed carbenetransferred cyclopropanation.…”

Dirhodium(II) Carbenes : The Chiral Product Cascade

“…Outside of two very recent preliminary reports from the Doyle group (Doyle et al, 1999b(Doyle et al, , 1999c, no widespread success with intramolecular cyclopropenation has been developed. These reactions often produce unstable fused cyclopropenes that undergo ring opening to vinylcarbenes that can react by a number of pathways, often giving rise to multiple products (Padwa et al, 1991(Padwa et al, , 1993 80 (71) 74 (77) 73 (88) 55 (73) 80 (90) 76 (83) 81 (71) 62 (85) 65 (78)…”