Asymmetric deprotonation of N-Boc-piperidines

Dynamics of Catalytic Resolution of 2-Lithio-N-Boc-piperidine by Ligand Exchange

“…In the presence of either (−)-sparteine ( 13 ) or bispidine 3 , TLC monitoring showed that transmetalation of S - 12 (73:27 er) to 7 was complete after 5 h; however, quenching with Me 3 SiCl afforded racemic 9 . This result is in contrast to an 87:13 er of 7 that was obtained by deprotonation using sec -BuLi in the presence of (−)-sparteine, 3a perhaps reflecting different mechanisms for the formation of 7 involving different types of lithium ligation in different solvents or in the presence of different amines. In THF in the absence of diamines for example, tin-lithium exchange occurs with complete retention of configuration.…”

“…1 The use of stoichiometric chiral ligands such as (−)-sparteine complexed to sec -BuLi, to effect enantioselective deprotonation represents one of the methods to generate scalemic organolithium compounds for use in asymmetric synthesis. 2 Unfortunately, effecting an asymmetric deprotonation on N -Boc-piperidines through the use of the chiral ligand (−)-sparteine is not as successful as with pyrrolidines, 3 but partial success (up to 88:12 er in reasonable yields) has been achieved with O’Brien’s diamine. 4 …”

Overview of Carbanion Dynamics and Electrophilic Substitutions in Chiral Organolithium Compounds

“…21,22 Note, however, that this deprotonation is much less successful with N -Boc piperidines. 23,24 Possible rationales for the steric course of the deprotonations are shown in the brackets, which assumes that the s -BuLi·sparteine complex is monomeric. 5,20,22,25 In both cases, the H Si proton ( i.e ., the proton that sits on the Si face of the triangle formed by the other 3 ligands on carbon) is removed selectively from a complex formed by coordination of the carbamate carbonyl to the lithium·sparteine chelate.…”

Direct α‐Functionalization of Saturated Cyclic Amines

“…They reported that the asymmetric a-functionalization of N-substituted piperidines is extremely sensitive to ligand sterics and in using hindered diamine ligands to bring about an enhancement in enantioselectivity, one concomitantly obtained products in lower than expected yields. [28] Thorough studies were thus performed to gain a better understanding of the mechanistic aspects of organolithium-mediated a-functionalization in the context of piperidines. [29] As previously performed in the analogous pyrrolidine system, the reaction of sBuLi and (À)-sparteine (L 1) with N-Boc-piperidine (42), known to yield poor results, was monitored by reactIR TM .…”