Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

Abstract

A series of P-stereogenic chiral phosphorus acids (CPAs) were synthesized to determine the requirements for efficient asymmetric organocatalysis. In order to eliminate the need for C2-symmetry in common CPAs, various scaffolds containing C1-symmetrical thiophosphorus acids were chosen. These new compounds were synthesized and evaluated in the asymmetric transfer hydrogenation of 2-phenylquinoline. Although the efficacy of the thiophosphorus acids was disappointing for this reaction, the work should be useful for developing structural design elements.

Enantioseparation of P-Stereogenic 1-Adamantyl Arylthiophosphonates and Their Stereospecific Transformation to 1-Adamantyl Aryl-H-phosphinates

“…The conversion was complete in all reactions, and products (( S )- 5 or ( R )- 7 ) were obtained with ee -s up to 10% ( Scheme 5 ). These preliminary experiments, especially in comparison with literature [ 39 , 40 , 42 ], show that P -stereogenic Brønsted acids without additional H -bond donors or acceptors may not induce a high level of enantiomeric excess, despite being active in these transfer hydrogenation reactions.…”

“…As the last step of the study, the applicability of ( S )-1-adamantyl phenylthiophosphonic acid (( S )- 2a ) was tested as chiral Brønsted acid catalyst. On the basis of other studies using P -stereogenic acids [ 39 , 40 , 42 ], the transfer hydrogenations of N -(4-methoxyphenyl)-1-phenylethanimine ( 4 ) and 2-methylquinoline ( 6 ) were selected as a test reaction, and Hantzsch ester ( 8 ) was the hydrogen source. The conversion was complete in all reactions, and products (( S )- 5 or ( R )- 7 ) were obtained with ee -s up to 10% ( Scheme 5 ).…”

“…A few studies suggested that C 1 -symmetric phopshothionates can also be used as organocatalysts, but in those instances, the catalyst scaffold contained other functional groups besides the P(S)OH moiety, and it was postulated that this combined activation is responsible for the asymmetric induction [ 38 , 39 , 40 , 41 ]. Very recently, Montchamp et al synthesized a series of cyclic thiophosphorus acids, and the organocatalytic activity of those compounds was tested [ 42 ].…”

Organophosphorus chemistry: from model to application

“…A series of P-stereogenic chiral thiophosphorus acids, such as a fused 1-hydroxytetrahydrophosphinine 1-sulfide, an oxaphosphinine sulfide analogue, and an azaphosphinine sulfide analogue were synthesized my Montchamp and Winters as potential organocatalysts [ 4 ]. The newly prepared thiophosphorus acids were not efficient in the asymmetric transfer hydrogenation of 2-phenylquinoline.…”