N‐Phosphinyl Imine Chemistry (I): Design and Synthesis of Novel N‐Phosphinyl Imines and their Application to Asymmetric aza‐Henry Reaction

Abstract

Novel chiral N-phosphinamide and N-phosphinyl imines have been designed, synthesized and applied to asymmetric aza-Henry reaction to give excellent chemical yields (92%- quant.) and diastereoselectivity (91% to >99%de). The reaction showed a great substrate scope in which aromatic/aliphatic aldehyde- and ketone-derived N-phosphinyl imines can be employed as electrophiles. The chiral N-phosphinamide can be stored at room temperature for more than 2 months without inert gas protection, and chiral N-phosphinyl imines were also proven to be highly stable at room temperature for a long period under inert gas protection. The N-phosphinyl group enabled the product purification to be performed simply by washing crude product with EtOAc and hexane. This reaction joined other eight GAP (Group-Assistant-Purification) chemistry processes that were developed in our laboratories. The absolute configuration has been unambiguously determined by converting a β-nitroamine product into a known N-Boc sample.

Asymmetric Carbamoyl Anion Additions to Chiral N-Phosphonyl Imines via the GAP Chemistry Process and Stereoselectivity Enrichments

“…In some cases, this washing procedure can even increase the diastereomeric and/or enantiomeric purity of the final product. 24 − 26 This simplified and more economical purification method has been termed GAP chemistry: A chemistry for organic synthesis that avoids traditional purification methods such as chromatography and/or recrystallization . GAP chemistry requires considerations in regard to (1) adequate stability and chemical reactivity of functional group-attached substrates; (2) solid products that are soluble in some solvents (e.g., THF and DCM), but not well soluble in some other solvents (e.g., petroleum ethers, hexane, and their cosolvents with EtOAc, etc.…”

Olefination of N‐Sulfinylimines under Mild Conditions

“…Based on the results obtained and on the vast amount already known about the Wittig–Horner reaction, we propose a similar mechanism for the olefination of N ‐sulfinylimines . After deprotonation, the phosphonate carbanion adds in a reversible way to the imine, with fast conversion between syn ( A 2 ) and anti ( A 1 ) intermediates.…”

“…Electrophilic imines have attracted much interest recently as a result of their simple preparation, their usefulness as directing groups, and their inherent reactivity in addition reactions in organic chemistry . In particular, N ‐protected imines, including N ‐sulfinyl, N ‐phosphonyl, N ‐phosphoryl, and N ‐phosphinyl imines, have been used as chiral auxiliaries in nucleophilic addition reactions. Given the importance of these electrophilic imines in stereoselective synthesis as chiral auxiliaries, it is surprising that their reactions with phosphorus ylides have not been studied, as their transformation into new useful functional groups after exercising their role as directing groups and/or chiral auxiliaries.…”

Cobalt- and iron-catalyzed regiodivergent alkene hydrosilylations

“…[3][4][5][12][13][14][15][16][17][18][19][20][21][22] With rational design of ligands, excellent reactivity, regioselectivity and even enantioselectivity can be readily achieved. Inspired by group-assisted purification (GAP) chemistry, [23][24][25][26][27][28] we hypothesized that incorporating the phosphoramide group into a ligand platform (metalla-GAP) might be an effective strategy to generate a novel and highly selective homogeneous catalyst. 29 Thus, in three synthetic steps, a series of tunable tridentate ligands are readily accessed (Scheme 2).…”