Thieme Chemistry Journal Awardees - Where Are They Now? Bridgehead Lithiated 9-Oxabispidines

Abstract

Bi-and tricyclic 9-oxabispidines are smoothly deprotonated at -78°C by s-BuLi at one of the bridgehead carbon atoms to give a-lithio ethers, which were trapped with electrophiles in good yields. Rearrangements to ring-contracted N,O-acetals occurred upon warming in the absence of an electrophile. The a-lithio ether intermediates are presumably stabilized by negative hyperconjugation.

The First Modular Route to Core‐Chiral Bispidine Ligands and Their Application in Enantioselective Copper(II)‐Catalyzed Henry Reactions

“…Modifications of the structure of 2 , for example, variation of the N ‐alkyl group as in 3 ,27 addition of substituents on the endo ‐fused piperidine as in 4 ,28 or replacement of this ring by an endo ‐oriented methyl group as in 7 ,29 usually resulted in significantly lower levels of chirality transfer. Formal exchange of the methylene bridge in 2 by an ether function lead to the structurally closely related 9‐oxabispidine 5 ,30, 31 which, however, underwent rearrangement in the strong basic milieu required for deprotonation reactions 32. Finally, bispidines of type 9 , carrying the chiral information in the side chains at the nitrogen atoms, could also not compete with 1 and 2 in terms of yield and stereocontrol 33.…”

“…[26] Modifications of the structure of 2,f or example, variation of the N-alkyl group as in 3, [27] addition of substituents on the endo-fused piperidine as in 4, [28] or replacement of this ring by an endo-oriented methyl group as in 7, [29] usually resulted in significantly lower levels of chirality transfer.F ormale xchange of the methylene bridge in 2 by an ether function lead to the structurally closely related9 -oxabispidine 5, [30,31] which, however,u nderwent rearrangement in the strong basic milieu required for deprotonation reactions. [32] Finally,b ispidines of type 9,c arrying the chiral informationi nt he side chains at the nitrogen atoms, could also not competew ith 1 and 2 in terms of yield and stereocontrol. [33] Thus, the core-chiral, N-methyl bispidine 2 with the endo-fused piperidine seems to meet best the minimum requirements for ah igh chirality transfer.I ts hould be noted that the bispidines 5 and 9,a lthough they gave insufficient results in deprotonation reactions, induced promising enantioselectivities in severalotherasymmetrictransformations.…”