P-Chiral, Monodentate Ferrocenyl Phosphines, Novel Ligands for Asymmetric Catalysis

Abstract

Eight P-chiral monodentate ferrocenyl phosphines (1a-h) were prepared in high enantiomeric excess (>95% ee in most cases) by way of an ephedrine-based oxazaphospholidine borane complex. Primary alkyl, secondary alkyl, and substituted aromatic substituents were successfully introduced at the phosphorus center, along with ferrocenyl and phenyl groups, generating phosphines of the general structure FcP(Ph)(R) (Fc = ferrocenyl, R = aryl, alkyl). The synthetic route employed provides facile access to a previously undeveloped class of chiral monophosphines. These compounds were evaluated as ligands in asymmetric catalytic reductive coupling of alkynes and aldehydes and were found to provide the desired chiral allylic alcohols with good regioselectivity and ee in many cases and with complete (E)-selectivity (>98:2) in all cases.

Catalytic Asymmetric Reductive Coupling of Alkynes and Aldehydes: Enantioselective Synthesis of Allylic Alcohols and α-Hydroxy Ketones

“…17 In contrast to our recent studies with chiral ferrocenyl monophosphines, enantioselectivities are significantly lower using NMDPP in couplings involving alkyl-CtC-alkyl alkynes (entry 15). 14 To illustrate the utility of this method further, allylic alcohols 9 and 13 were converted to R-hydroxy ketones via ozonolysis. Enantiomeric purity was preserved in both cases, giving 16 (89% ee), whose TBS ether was developed by Masamune for asymmetric aldol reactions, 18 and 17 (96% ee), whose R-amino-R′-hydroxy pattern is found in molecules targeted against trypanosomes, parasites that cause African sleeping sickness upon transmission from tsetse flies, 19 and in aerothionin natural products with antituberculosis activity.…”

Regioselectivity and enantioselectivity in nickel-catalysed reductive coupling reactions of alkynes

“…The presence of an olefin tether was sufficient to overcome an inherent steric preference for the B regioisomer (entry 4, Table 3). 26 Heteroatoms were also well tolerated and augment the versatility of this directed transformation (entries 6-8, Table 3). …”

Reaction of Alkynes

“…In contrast to the reaction with aldehydes, Et 3 B delivers the ethyl group at the distal carbon of alkynes for the reaction with imines (Scheme 4.37(b)) [85]. In this way asymmetric induction is achieved [86], and the technique has been applied to the total synthesis of (À)-terpestacin (a natural product) (Scheme 4.38) [87].…”