Chiral Phosphoric Acids: New Organocatalysts for Reductive Amination

Introduction

Representative Applications

Product Information

Introduction
BINOL-derived phosphoric acids have been frequently appearing in literature as useful organocatalysts. These compounds are capable of catalyzing a range of interesting processes: reductive aminations, Pictet-Spengler reactions, aza-Diels-Alder reactions, addition reactions, and cascade reactions are all effected with excellent enantioselectivites.

Representative Applications

Reductive Amination

An enantioselective reductive amination has been reported by several research groups.1,2 Rueping first reported that the phosphoric acid 674605 catalyzed the reduction of an imine with a Hantzsch ester in good enantiomeric excess.



List reported an improvement to this method using 689890 and highlighted the ability to perform a one-pot process from aldehyde to amine in enantiomeric excesses up to 92%.



MacMillan finally reported a one-pot, direct, reductive amination with broad substrate scope that enables the effective reductive amination of a range of methyl ketones and aryl amines.3 It is even possible to obtain good enantiomeric excess with 2-butanone, as the MacMillan TiPSY catalyst, 674745, can distinguish between a methyl group and an ethyl group, delivering the product in high enantiomeric excess.

References: Rueping, M. et al. Org. Lett. 2005, 7, 3781. Hoffmann, S. et al. Angew. Chem. Int. Ed. 2005, 44, 7424. Storer, R. I. et al. J. Am. Chem. Soc. 2006, 128, 84.

Back to Top

Pictet-Spengler Reaction

List and coworkers reported a direct Pictet-Spengler reaction with a range of aldehydes using organocatalyst (R)-TRIP, 689890, to form isoquinolines in high yields and enantiomeric excess. A geminally disubstituted tryptamine is needed, but this limitation does not significantly affect the utility of this process.

Reference: Seayad, J. et al. J. Am. Chem. Soc. 2006, 128, 1086.

Back to Top

Aza-Diels-Alder Reaction

(R)-TRIP is also capable of effecting the aza-Diels-Alder reaction of aldimines with Danishefsky’s diene to afford piperidinone derivatives with high enantioselectivity. The addition of acetic acid improves both reactivity and enantioselectivity.

Reference: Akiyama, T. et al. Synlett 2006, 141.

Back to Top

Addition Reaction

Antilla and co-workers reported on the use of VAPOL derived phosphoric acid derivative 675512 in the addition of sulfonamides to Boc-protected aryl imines, giving rise to protected aminals in excellent enantioselectivities.

Reference: Rowland, G. B. et al. J. Am. Chem. Soc. 2005, 127, 15696.

Back to Top

Cascade Reaction

Recently, List reported an elegant, highly enantioselective cascade reaction. The synthesis of pharmaceutically relevant 3-substituted cyclohexylamines from 2,6-diketones via an aldolization-dehydration-conjugate reduction-reductive amination cascade that is catalyzed by the chiral Brønsted acid (R)-TRIP and accelerated by the achiral amine substrate, which is ultimately incorporated into the product.

Reference: Zhou, J.; List, B. J. Am. Chem. Soc. 2007, 129, 7498.

Product Information

Product #	Product Name	Structure	Add to Cart
248932	(R)-(–)-1,1'-Binaphthyl-2,2'-diyl hydrogenphosphate
248940	(S)-(+)-1,1'-Binaphthyl-2,2'-diyl hydrogenphosphate
674745	(R)-(–)-3,3'-Bis(triphenylsilyl)-1,1'-binaphthyl-2,2'-diyl hydrogenphosphate
680184	(S)-(+)-3,3'-Bis(triphenylsilyl)-1,1'-binaphthyl-2,2'-diyl hydrogenphosphate
675512	(R)-(–)-VAPOL hydrogenphosphate
674605	(R)-3,3'-Bis[3,5-bis(trifluoromethyl)phenyl]-1,1'-binaphthyl-2,2'-diyl hydrogenphosphate
681520	(S)-3,3'-Bis[3,5-bis(trifluoromethyl)phenyl]-1,1'-binaphthyl-2,2'-diyl hydrogenphosphate
689890	(R)-3,3'-Bis(2,4,6-triisopropylphenyl)-1,1'-binaphthyl-2,2'-diyl hydrogenphosphate
689785	(S)-3,3'-Bis(2,4,6-triisopropylphenyl)-1,1'-binaphthyl-2,2'-diyl hydrogenphosphate
695718	(R)-3,3'-Bis(9-anthracenyl)-1,1'-binaphthyl-2,2'-diyl hydrogenphosphate

Back to Top