Prolinol as a Chiral Auxiliary in Organophosphorus Chemistry

Abstract

Several strategies for the development of the synthesis of Pchiral organophosphorus compounds with (L)-prolinol as a source of chirality have been examined. A reaction of L-prolinol with a set of different alkyl/arylphosphonous acid diamides led in most of the cases to the quantitative formation of the appropriate bicyclic oxazaphospholidines with complete dia-stereo and enantioselectivity. The latter were reacted with BH 3 complex and the formed borane analogues were submitted to structural modifications leading to tertiary phosphine-boranes. Additionally, the effectiveness of oxazaphospholidines as ligands in transition metal asymmetric catalysis has been tested in hydrogenation of dehydroaminoacid esters and imine.

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

“…Subsequently, P(V) electrophiles bearing alkyl substituents were submitted to the optimized desymmetrization conditions. Methyl, ethyl, and n-hexyl derived substrates were all competent electrophiles in the desymmetrization with the desired products (26)(27)(28) being obtained in 88-97 % yields and 90 : 10-93 : 7 e.r. Interestingly even more sterically demanding substituents on P, such as iso-propyl, could also be accommodated with the resulting enantioenriched product (29) being obtained in 79 % yield and 94 : 6 e.r.…”

“…The first approach is classical resolution and/or separation of diastereomers or enantiomers by chromatography (Scheme 1B, i) [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) [14–31] . 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] .…”

Concept-Driven Chemoselective O/N-Derivatization of Prolinol: A Bee-Line Approach to Access Organocatalysts

“…The crude reaction mixture was extracted with EtOAc (3 × 50 mL), and the combined organic layer was washed with brine solution. The organic layer was dried using anhydrous Na 2 SO 4 and concentrated to provide the pure product as a colorless viscous liquid (2.5 g, 82%), which was used without any further purification. , R f (EtOAc/petroleum ether 3:7) = 0.25; [α] D = +6.4 ( c 0.9 in CHCl 3 ); 1 H NMR (400 MHz, CDCl 3 ): δ 4.14 (dd, J = 11.3, 3.1 Hz, 1H), 3.67 (dd, J = 11.3, 3.1 Hz, 1H), 3.41–3.28 (m, 1H), 3.07 (m, 1H), 2.89 (m, 1H), 2.06–1.77 (m, 4H); 13 C­{ 1 H} NMR (101 MHz, CDCl 3 ): δ 66.8, 60.1, 55.2, 27.2, 23.7. HRMS (ESI + ): m / z calcd for [C 5 H 11 NO + H] + , 102.0919; found, 102.0923, Δ = 4 ppm.…”

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.…”