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Chemistry > Chemical Synthesis > Technology Spotlights > Chiral Phosphoric Acids
Chemical Synthesis

Chiral Phosphoric Acids

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.

Reductive Amination 674605 Image

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%.

Reductive Amination 689890 Image

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.

Reductive Amination 674745 Image

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

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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.

Pictet-Spengler Reaction 689890 Image

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

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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.

Aza-Diels-Alder Reaction Image

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

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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.

Addition Reaction Image

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

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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.

Cascade Reaction Image

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


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Product Information

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

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