Abstract
Ten novel hydrogen-bonding catalysts based on open-chain PV-amides of BINOL and chinchona alkaloids as well as three catalysts based on rigid cis-PV-cyclodiphosphazane amides of N1,N1-dimethylcyclohexane-1,2-diamine have been developed. Employed in the asymmetric Michael addition of 2-hydroxynaphthoquinone to β-nitrostyrene, the open-chain 9-epi-aminochinchona-based phosphorus amides show a high catalytic activity with almost quantitative yields of up to 98% and enantiomeric excesses of up to 51%. The cyclodiphosphazane catalysts show the same high activity and give improved enantiomeric excesses of up to 75%, thus representing the first successful application of a cyclodiphosphazane in enantioselective organocatalysis. DFT computations reveal high hydrogen-bonding strengths of cyclodiphosphazane PV-amides compared to urea-based catalysts. Experimental results and computations on the enantiodetermining step with cis-cyclodiphosphazane 14a suggest a strong bidentate H-bond activation of the nitrostyrene substrate by the catalyst.
Highlights
Organocatalysis has gained great impact in promoting highly enantioselective [1,2,3,4] and eco-friendly [5] reactions
Synthesis of chiral open-chain PV-amides. We evaluated both BINOL and chinchona alkaloids as chiral backbones
Exchanging one of the N1,N1-dimethylaminocyclohexylamino groups for an aniline moiety, as in catalyst 16, supports this. This sterically less demanding catalyst produced yields and selectivities (95% yield, 67% ee, Table 4) close to those of 14a. While both structural motifs are efficient promoters of the reaction, open-chain phosphorus amides 1–7f are outperformed by the more selective cyclodiphosphazanes 14a/16, which can be attributed to the greater structural rigidity of the latter combined with a stronger hydrogen bonding
Summary
Organocatalysis has gained great impact in promoting highly enantioselective [1,2,3,4] and eco-friendly [5] reactions. The majority of non-specific hydrogen-bonding catalysts are based on the (thio)urea motif (I, Figure 1) [9,10]. Gale et al demonstrated that the same phosphoric triamides effectively act as anion transporters by hydrogen bonding [19]. These characteristics and the increased steric bulk of “3-D”-PV compared to “2-D” urea or squaramides make phosphorus triamides excellent candidates for asymmetric (HB) organocatalysts. Computations of the H-bonding properties of both P-triamide III and cyclodiphosphazane IV and their comparison to the “classic” motifs I and II suggest a slightly larger spacing and are reported . We report the synthesis of chiral variants of the catalyst motifs III and IV and their successful application in the organocatalytic addition of 2-hydroxynaphthoquinone to β-nitrostyrene as a test reaction
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call