Stereocontrolled Radical Thiophosphorylation

Abstract

The first practical, fully stereoselective P­(V)-radical hydrophosphorylation is presented herein by using simple, limonene-derived reagent systems. A set of reagents have been developed that upon radical initiation react smoothly with olefins and other radical acceptors to generate P-chiral products, which can be further diversified (with conventional 2e– chemistry) to a range of underexplored bioisosteric building blocks. The reactions have a wide scope with excellent chemoselectivity, and the unexpected stereochemical outcome has been supported computationally and experimentally. Initial ADME studies are suggestive of the promising properties of this rarely explored chemical space.

Radical reactions enabled by polyfluoroaryl fragments: photocatalysis and beyond

“…The reaction of non-activated alkenes 73.1 and limonene-derived chiral P( v ) reagents 73.2-3 proceeded under elevated temperatures in the presence of tris(trimethylsilyl)silane and initiator to form the hydrophosphorylation product 73.4 (Scheme 73). 180 The reaction proceeds through the homolytic substitution at the sulfur atom by the silyl radical generated in the presence of AIBN initiator and has a chain character. The use of a fluorinated thio-group made it possible to avoid the use of a more toxic PhSe-group.…”

Second Generation Catalytic Enantioselective Nucleophilic Desymmetrization at Phosphorus (V): Improved Generality, Efficiency and Modularity

“…[13] A second approach revolves around the use of labile chiral auxiliaries which can be displaced by sequential diastereoselective nucleophilic additions to afford enantioenriched P(V) species (Scheme 1B, ii). [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] Thirdly, chiral, yet racemic at P(V) electrophiles bearing a single leaving group (and often possessing a chiral (single enantiomer) sidechain) can be coupled diastereoselectively to enantiopure nucleophiles employing chiral catalysts (Scheme 1B, iii). [32][33] A subsequent approach involves the direct functionalization of secondary phosphine oxides (SPO) by means of a metal catalyst bearing chiral ligands to obtain tertiary phosphine oxides.…”

Second Generation Catalytic Enantioselective Nucleophilic Desymmetrization at Phosphorus (V): Improved Generality, Efficiency and Modularity

“…[13] A second approach revolves around the use of labile chiral auxiliaries which can be displaced by sequential diastereoselective nucleophilic additions to afford enantioenriched P(V) species (Scheme 1B, ii). [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] Thirdly, chiral, yet racemic at P(V) electrophiles bearing a single leaving group (and often possessing a chiral (single enantiomer) sidechain) can be coupled diastereoselectively to enantiopure nucleophiles employing chiral catalysts (Scheme 1B, iii). [32][33] A subsequent approach involves the direct functionalization of secondary phosphine oxides (SPO) by means of a metal catalyst bearing chiral ligands to obtain tertiary phosphine oxides.…”