Synthesis of optically active 1,4-benzoxazine derivatives using palladium-catalyzed coupling kinetic resolution

A novel coupling kinetic resolution has been developed by employing commercially available reagents, such as Pd(OOCCF3)2–(S)-BINAP, which is a simple and convenient protocol that enables the formation of a highly important, novel class of optically active trans-1,4-benzoxazine derivatives and optically active trans-recovered starting materials with moderate selectivity (s).

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(+)-trans-4a,10a-10-Tosyl-2,3,4,4a,10,10a-hexahydro-1H-phenoxazineC19H21NSO3Ee = 32%[α]D25=+13.7 (c 1.3, CHCl3)Source of chirality: coupling kinetic resolution

(+)-trans-3a,9a-9-Tosyl-1,2,3,3a,9,9a-hexahydrobenzo[b]cyclopenta[e][1,4]oxazineC18H19NO3SEe = 40%[α]D25=+29.4 (c 1.3, CHCl3)Source of chirality: coupling kinetic resolution

(+)-trans-4a,10a-8-Chloro-10-tosyl-2,3,4,4a,10,10a-hexahydro-1H-phenoxazineC19H20NO3SClEe = 36%[α]D25=+67.0 (c 2.0, CHCl3)Source of chirality: coupling kinetic resolution

(+)-trans-8-Methoxy-10-tosyl-2,3,4,4a,10,10a-hexahydro-1H-phenoxazineC20H23NO4SEe = 26%[α]D25=+10.9 (c 0.2, CHCl3)Source of chirality: coupling kinetic resolution

(+)-trans-4a,10a-8-Phenyl-10-tosyl-2,3,4,4a,10,10a-hexahydro-1H-phenoxazineC25H25NO3SEe = 39%[α]D25=+8.7 (c 0.3, CHCl3)Source of chirality: coupling kinetic resolution

(−)-trans-(5a,11a,Z)-12-Tosyl-6,7,10,11,11a,12-hexahydro-5aH-benzo[b]cycloocta[e][1,4]oxazineC21H23NO3SEe = 43%[α]D25=-12.9 (c 0.6, CHCl3)Source of chirality: coupling kinetic resolution

(+)-trans-3a,9a-7-Methoxy-9-tosyl-1,2,3,3a,9,9a-hexahydrobenzo[b]cyclopenta[e][1,4]oxazineC19H21NO4SEe = 24%[α]D25=+48.7 (c 1.0, CHCl3)Source of chirality: coupling kinetic resolution

(+)-trans-7-Methyl-9-tosyl-1,2,3,3a,9,9a-hexahydrobenzo[b]cyclopean ta[e][1,4]oxazineC19H21NO3SEe = 42%[α]D25=+16.9 (c 0.2, CHCl3)Source of chirality: coupling kinetic resolution

(+)-trans-N-(2-(2-Bromophenoxy)cyclohexyl)-4-methylbenzenesulfonamideC19H22NO3SBrEe = 69%[α]D25=+33.7 (c 0.2, CHCl3)Source of chirality: coupling kinetic resolution

(−)-trans-N-(2-(2-Bromophenoxy)cyclopentyl)-4-methylbenzenesulfonamideC18H20NO3SBrEe = 22%[α]D25=-22.9 (c 3.5, CHCl3)Source of chirality: coupling kinetic resolution

(−)-trans-N-(2-(2-Bromo-4-chlorophenoxy)cyclohexyl)-4-methylbenzenesulfonamideC19H21NO3SClBrEe = 20%[α]D25=-21.1 (c 3.5, CHCl3)Source of chirality: coupling kinetic resolution

(+)-trans-N-(2-(2-Bromo-4-methoxyphenoxy)cyclohexyl)-4-methylbenzenesulfonamideC20H24NO4SBrEe = 16%[α]D25=+13.3 (c 0.3, CHCl3)Source of chirality: coupling kinetic resolution

(+)-trans-N-(2-(3-Bromobiphenyl-4-yloxy)cyclohexyl)-4-methylbenzenesulfonamideC25H26NO3BrSEe = 20%[α]D25=+5.0 (c 0.2, CHCl3)Source of chirality: coupling kinetic resolution

(−)-trans-N-((Z)-8-(2-Bromo-4-phenoxy)cyclooct-4-enyl)-4-methylbenzenesulfonamideC21H24NO3SBrEe = 10%[α]D25=-6.9 (c 0.2, CHCl3)Source of chirality: coupling kinetic resolution

(−)-trans-N-(2-(2-Bromo-4-methoxyphenoxy)cyclopentyl)-4-methylbenzenesulfonamideC19H22NO4SBrEe = 28%[α]D25=-11.2 (c 1.3, CHCl3)Source of chirality: coupling kinetic resolution

(−)-trans-N-(2-(2-Bromo-4-methylphenoxy)cyclopentyl)-4-methylbenzenesulfonamideC19H21NSO3Ee = 18%[α]D25=-19.5 (c 1.0, CHCl3)Source of chirality: coupling kinetic resolution