Chiral α-branched mono phosphine auxiliaries, reversal of sense of asymmetric induction upon substitution

A group of 10 (mono- or bis-) α-chiral mono phosphine ligands was synthesized from enantiopure phosphepine sulfide 3 by one or two subsequential highly diastereoselective α-deprotonation/alkylation steps, followed by desulfuration with Raney nickel. Their relative configuration was determined by X-ray crystal structure analysis. The new monophosphine ligands were tested in asymmetric hydrogenation, hydroboration, and Suzuki–Miyaura coupling showing asymmetric inductions up to 91% ee. In the case of hydrogenation, clear evidence was found that enantioselectivity is substantially controlled through α-C chirality rather than through biaryl chirality, which was demonstrated by a change of the sense of asymmetric induction upon change of substituents.

Ligands L were applied in asymmetric catalysis (hydrogenation, hydroboration, and Suzuki–Miyaura cross-coupling) affording asymmetric inductions up to 91% ee.Figure optionsDownload as PowerPoint slide

(S)-4-Phenyl-4,5-dihydro-3H-dinaphtho[2,1-c;1′,2′-e]phosphepine sulfideC28H21PSEe = 100%[α]D20=+99.6 (c 0.590, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (Sa)

(S,Sa,Rp)-3-Methyl-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c;1′,2′-e]phosphepine sulfideC29H23PSEe = 100%[α]D20=+37.3 (c 0.490, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (S,Sa,Rp)

(S,Sa,Sp)-3-Methyl-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c;1′,2′-e]phosphepine sulfideC29H23PSEe = 100%[α]D20=+48.0 (c 0.250, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (S,Sa,Sp)

(S,S,Sa)-3,5-Dimethyl-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c;1′,2′-e]phosphepine sulfideC30H25PSEe = 100%[α]D20=+122 (c 0.730, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (S,S,Sa)

(S,Sa,Rp)-3-Ethyl-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c;1′,2′-e]phosphepine sulfideC30H25PSEe = 100%[α]D20=+314 (c 0.500, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (S,Sa,Rp)

(S,Sa,Sp)-3-Ethyl-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c;1′,2′-e]phosphepine sulfideC30H25PSEe = 100%[α]D20=+533 (c 0.260, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (S,Sa,Sp)

(S,S,Sa)-3,5-Diethyl-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c;1′,2′-e]phosphepine sulfideC32H29PSEe = 100%[α]D20=+143 (c 0.690, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (S,S,Sa)

(S,Sa,Rp)-3-Isopropyl-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c;1′,2′-e]phosphepine sulfideC31H27PSEe = 100%[α]D20=+540 (c 0.285, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (S,Sa,Rp)

(S,S,Sa)-3,5-Diisopropyl-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c;1′,2′-e]phosphepine sulfideC34H33PSEe = 100%[α]D20=+1524 (c 0.100, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (S,S,Sa)

(S,Sa,Rp)-3-Benzyl-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c;1′,2′-e]phosphepine sulfideC35H27PSEe = 100%[α]D20=+324 (c 0.300, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (S,Sa,Rp)

(S,Sa,Sp)-3-Benzyl-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c;1′,2′-e]phosphepine sulfideC35H27PSEe = 100%[α]D20=+397 (c 0.490, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (S,Sa,Sp)

(S,S,Sa)-3,5-Dibenzyl-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c;1′,2′-e]phosphepine sulfideC42H33PSEe = 100%[α]D20=+947 (c 0.325, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (S,S,Sa)

(S,Sa,Sp)-3-Methyl-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c;1′,2′-e]phosphepineC29H23PEe = 100%[α]D20=-90 (c 0.545, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (S,Sa,Sp)

(S,S,Sa)-3,5-Dimethyl-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c;1′,2′-e]phosphepineC30H25PEe = 100%[α]D20=+95 (c 0.55, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (S,S,Sa)

(S,Sa,Sp)-3-Ethyl-4-phenyl-4,5-dihydro-3H- dinaphtho[2,1-c;1′,2′-e]phosphepineC30H25PEe = 100%[α]D20=+82 (c 0.21, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (S,Sa,Sp)

(S,S,Sa)-3,5-Diethyl-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c;1′,2′-e]phosphepineC32H29PEe = 100%[α]D20=+145 (c 0.62, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (S,S,Sa)

(S,Sa,Sp)-3-Isopropyl-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c;1′,2′-e]phosphepine borane complexC31H27P BH3Ee = 100%[α]D20=+222 (c 0.343, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (S,Sa,Sp)

(S,S,Sa)-3,5-Diisopropyl-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c;1′,2′-e]phosphepine borane complexC34H33P BH3Ee = 100%[α]D20=+184 (c 0.12, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (S,S,Sa)

(S,Sa,Sp)-3-Benzyl-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c;1′,2′-e]phosphepineC35H27PEe = 100%[α]D20=+163 (c 0.375, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (S,Sa,Sp)

(S,S,Sa)-3,5-Dibenzyl-4-phenyl-4,5-dihydro-3H-dinaphtho[2,1-c;1′,2′-e]phosphepineC42H33PEe = 100%[α]D20=+417 (c 0.505, CHCl3)Source of chirality: diastereoselective synthesisAbsolute configuration: (S,S,Sa)