A One-Pot Procedure for the Synthesis of α-Amino Phosphonates from Alkynes

Abstract

A new and highly flexible procedure for the synthesis of α,α-disubstituted α-amino phosphonates is described with disubstituted alkynes, primary amines and diethyl or dimethyl phosphite as starting materials. The reaction sequence, which is performed as a one-pot operation, starts with a Cp 2 TiMe 2 -catalyzed hydroamination of the alkyne. A sub-

Group‐IV Metal Complexes as Hydroamination Catalysts

“…Since the combination of all the studies described in this review definitely proves that titanium complex catalyzed inter‐ and intramolecular hydroamination reactions represent reliable new synthetic transformations it is not surprising that initial applications of corresponding procedures for the synthesis of biologically interesting compounds have already appeared in the literature 28,29…”

Group‐IV Metal Complexes as Hydroamination Catalysts

“…Since the combination of all the studies described in this review definitely proves that titanium complex catalyzed inter‐ and intramolecular hydroamination reactions represent reliable new synthetic transformations it is not surprising that initial applications of corresponding procedures for the synthesis of biologically interesting compounds have already appeared in the literature 28,29…”

A One-Pot Approach to 2-Substituted-2-(Dimethoxyphosphoryl)-Pyrrolidines from Substituted tert-Butyl 4-Oxobutylcarbamates and Trimethyl Phosphite

“…24 In addition, an amine containing alkynyl bond compound has been converted to piperidine α-tertiary amino phosphonates and their derivatives through the Cp 2 TiMe 2 prompted intramolecular hydroamination and followed phosphorylation process, but the intramolecular hydroamination needs 72 h (Figure 2, c). 25 Similarly, the alkyne amination/phosphorylation catalyzed by copper converted the secondary aminoalkynes to various cyclic αaminophosphonate derivatives (Figure 2, d). 26 δ-Amino αdiazo β-ketophosphonate has also been converted to 3-oxo pyrrolidine phosphonate via an intramolecular metal carbenoid N−H insertion (Figure 2, e).…”

“…Colorless oil (371 mg, 44%). [α] D 25 −2.6 (c 1.00, CHCl 3 ); IR (film) ν max 3376,2931,1715,1256,1171,841, 778 cm −1 ; 1 H NMR (400 MHz, CDCl 3 ) δ 7. 29−7.21 (m, 1H), 7.12−7.07 (m, 1H), 7.03−6.97 (m, 2H), 4.80 (s, 1H), 4.32−4.23 (m, 1H), 3.93−3.76 (m, 2H), 3.28−3.14 (m, 2H), 2.36−2.32 (m, 3H), 2.03−1.79 (m, 2H), 1.46 (s, 9H), 0.98 (s, 9H), 0.09 (s, 6H) ppm; 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 210.…”

Hydroamination: Direct Addition of Amines to Alkenes and Alkynes

“…Imines can be utilized as precursors for α-amino phosphonates that can serve as building blocks for phosphorous-containing peptide mimetics. Nucleophilic additions of dialkyl phosphites to imines, generated via inter- or intramolecular alkyne hydroamination, were performed in a one-pot procedure using catalytic amounts of Me 2 AlCl (Scheme ) . Hydroamination reactions with p -anisidine or benzhydryl amine gave access to the primary α-amino phosphonates via oxidative deprotection with ceric ammonium nitrate (CAN) or hydrogenolysis with H 2 /Pd/C (Scheme ).…”

Group‐IV Metal Complexes as Hydroamination Catalysts

“…Since the combination of all the studies described in this review definitely proves that titanium complex catalyzed inter‐ and intramolecular hydroamination reactions represent reliable new synthetic transformations it is not surprising that initial applications of corresponding procedures for the synthesis of biologically interesting compounds have already appeared in the literature 28,29…”

A One-Pot Approach to 2-Substituted-2-(Dimethoxyphosphoryl)-Pyrrolidines from Substituted tert-Butyl 4-Oxobutylcarbamates and Trimethyl Phosphite

“…24 In addition, an amine containing alkynyl bond compound has been converted to piperidine α-tertiary amino phosphonates and their derivatives through the Cp 2 TiMe 2 prompted intramolecular hydroamination and followed phosphorylation process, but the intramolecular hydroamination needs 72 h (Figure 2, c). 25 Similarly, the alkyne amination/phosphorylation catalyzed by copper converted the secondary aminoalkynes to various cyclic αaminophosphonate derivatives (Figure 2, d). 26 δ-Amino αdiazo β-ketophosphonate has also been converted to 3-oxo pyrrolidine phosphonate via an intramolecular metal carbenoid N−H insertion (Figure 2, e).…”

“…Colorless oil (371 mg, 44%). [α] D 25 −2.6 (c 1.00, CHCl 3 ); IR (film) ν max 3376,2931,1715,1256,1171,841, 778 cm −1 ; 1 H NMR (400 MHz, CDCl 3 ) δ 7. 29−7.21 (m, 1H), 7.12−7.07 (m, 1H), 7.03−6.97 (m, 2H), 4.80 (s, 1H), 4.32−4.23 (m, 1H), 3.93−3.76 (m, 2H), 3.28−3.14 (m, 2H), 2.36−2.32 (m, 3H), 2.03−1.79 (m, 2H), 1.46 (s, 9H), 0.98 (s, 9H), 0.09 (s, 6H) ppm; 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 210.…”

Hydroamination: Direct Addition of Amines to Alkenes and Alkynes

“…Imines can be utilized as precursors for α-amino phosphonates that can serve as building blocks for phosphorous-containing peptide mimetics. Nucleophilic additions of dialkyl phosphites to imines, generated via inter- or intramolecular alkyne hydroamination, were performed in a one-pot procedure using catalytic amounts of Me 2 AlCl (Scheme ) . Hydroamination reactions with p -anisidine or benzhydryl amine gave access to the primary α-amino phosphonates via oxidative deprotection with ceric ammonium nitrate (CAN) or hydrogenolysis with H 2 /Pd/C (Scheme ).…”

Group‐IV Metal Complexes as Hydroamination Catalysts

“…Since the combination of all the studies described in this review definitely proves that titanium complex catalyzed inter‐ and intramolecular hydroamination reactions represent reliable new synthetic transformations it is not surprising that initial applications of corresponding procedures for the synthesis of biologically interesting compounds have already appeared in the literature 28,29…”

A One-Pot Approach to 2-Substituted-2-(Dimethoxyphosphoryl)-Pyrrolidines from Substituted tert-Butyl 4-Oxobutylcarbamates and Trimethyl Phosphite

“…24 In addition, an amine containing alkynyl bond compound has been converted to piperidine α-tertiary amino phosphonates and their derivatives through the Cp 2 TiMe 2 prompted intramolecular hydroamination and followed phosphorylation process, but the intramolecular hydroamination needs 72 h (Figure 2, c). 25 Similarly, the alkyne amination/phosphorylation catalyzed by copper converted the secondary aminoalkynes to various cyclic αaminophosphonate derivatives (Figure 2, d). 26 δ-Amino αdiazo β-ketophosphonate has also been converted to 3-oxo pyrrolidine phosphonate via an intramolecular metal carbenoid N−H insertion (Figure 2, e).…”

“…Colorless oil (371 mg, 44%). [α] D 25 −2.6 (c 1.00, CHCl 3 ); IR (film) ν max 3376,2931,1715,1256,1171,841, 778 cm −1 ; 1 H NMR (400 MHz, CDCl 3 ) δ 7. 29−7.21 (m, 1H), 7.12−7.07 (m, 1H), 7.03−6.97 (m, 2H), 4.80 (s, 1H), 4.32−4.23 (m, 1H), 3.93−3.76 (m, 2H), 3.28−3.14 (m, 2H), 2.36−2.32 (m, 3H), 2.03−1.79 (m, 2H), 1.46 (s, 9H), 0.98 (s, 9H), 0.09 (s, 6H) ppm; 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 210.…”

Hydroamination: Direct Addition of Amines to Alkenes and Alkynes

“…Imines can be utilized as precursors for α-amino phosphonates that can serve as building blocks for phosphorous-containing peptide mimetics. Nucleophilic additions of dialkyl phosphites to imines, generated via inter- or intramolecular alkyne hydroamination, were performed in a one-pot procedure using catalytic amounts of Me 2 AlCl (Scheme ) . Hydroamination reactions with p -anisidine or benzhydryl amine gave access to the primary α-amino phosphonates via oxidative deprotection with ceric ammonium nitrate (CAN) or hydrogenolysis with H 2 /Pd/C (Scheme ).…”