Synthesis of JOSIPHOS-type ligands via a diastereoselective three-component reaction and their application in asymmetric rhodium-catalyzed hydroborations

The recently reported diastereoselective three-component reaction for the synthesis of chiral propargylamines was used for a new stereoselective synthesis of JOSIPHOS-type ligands 2a–d. The present synthesis gives the desired diphosphines in good yields without the need of resolution. Ligands 2a–d were applied to the rhodium-catalyzed hydroboration of styrene.

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(R)-1-Ferrocenyl-1-[(S)-2-methoxymethyl-1-pyrrolidinyl]-3-trimethylsilyl-2-propyneC22H31FeNOSiEe = >99%[α]D = +181.9 (c 1.56, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (R),(S)

(R)-1-Ferrocenyl-1-[(S)-2-methoxymethyl-1-pyrrolidinyl]-4-methoxy-2-butyneC21H27FeNO2Ee = >99%[α]D = +134.4 (c 4.15, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (R),(S)

(R)-1-Ferrocenyl-1-[(S)-2-methoxymethyl-1-pyrrolidinyl]-4,4-dimethyl-2-pentyneC23H31FeNOEe = >99%[α]D = +139.4 (c 0.49, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (R),(S)

(R)-1-Ferrocenyl-1-[(S)-2-methoxymethyl-1-pyrrolidinyl]-2-propyneC19H23FeNOEe = >99%[α]D = +87.3 (c 3.29, CHCl3)Source of chirality: diastereomerically pure starting materialAbsolute configuration: (R),(S)

(R)-1-Ferrocenyl-1-[(S)-2-methoxymethyl-1-pyrrolidinyl]-2-propaneC19H27FeNOEe = >99%[α]D = −61.8 (c 0.86, CHCl3)Source of chirality: diastereomerically pure starting materialAbsolute configuration: (R),(S)

(SFc)-1-Diphenylphosphano-2-[α-(R)-(N,N-dimethylamino)propyl]ferrocene borane complexC27H33BFeNPEe = >99%[α]D = −304.7(c 0.54, CH2Cl2)Source of chirality: diastereoselective synthesisAbsolute configuration: (SFc,R)

(SFc)-1-Dicyclohexylphosphano-2-[α-(R)-(N,N-dimethylamino)propyl]ferrocene borane complexC27H45BFeNPEe = >99%[α]D = −144.8 (c 0.29, CH2Cl2)Source of chirality: diastereoselective synthesisAbsolute configuration: (SFc,R)

(SFc)-1-Diphenylphosphano-2-[α-(R)-(dicyclohexylphosphano)propyl]ferrocene bis-borane complexC37H52B2FeP2Ee = >99%[α]D = −194.4 (c 0.39, CH2Cl2)Source of chirality: synthesis with complete retention of configurationAbsolute configuration: (SFc,R)

(SFc)-1-Diphenylphosphano-2-[α-(R)-(diphenylphosphano)propyl]ferrocene bis-borane complexC37H40B2FeP2Ee = >99%[α]D = −212.1 (c 0.43, CH2Cl2)Source of chirality: synthesis with complete retention of configurationAbsolute configuration: (SFc,R)

(SFc)-1-Dicyclohexylphosphano-2-[α-(R)-(dicyclohexylphosphano)propyl]ferrocene bis-borane complexC37H64B2FeP2Ee = >99%[α]D = −29.9 (c 0.36, CH2Cl2)Source of chirality: synthesis with complete retention of configurationAbsolute configuration: (SFc,R)

(SFc)-1-Dicyclohexylphosphano-2-[α-(R)-(diphenylphosphano)propyl]ferrocene bis-borane complexC37H52B2FeP2Ee = >99%[α]D = −44.4 (c 0.27, CH2Cl2)Source of chirality: synthesis with complete retention of configurationAbsolute configuration: (SFc,R)