US 11,926,589 B2
Process for the synthesis of non-racemic cyclohexenes
Sarah Reisman, Pasadena, CA (US); Michael Rombola, Pasadena, CA (US); Carolyn L. Ladd, Pasadena, CA (US); Martin John McLaughlin, Ludwigshafen (DE); Stephan Zuend, Hayward, CA (US); and Roland Goetz, Ludwigshafen (DE)
Assigned to BASF CORPORATION, Florham Park, NJ (US); and CALIFORNIA INSTITUTE OF TECHNOLOGY, Pasadena, CA (US)
Appl. No. 17/625,414
Filed by BASF CORPORATION, Florham Park, NJ (US); and California Institute of Technology, Pasadena, CA (US)
PCT Filed Jul. 6, 2020, PCT No. PCT/US2020/040856
§ 371(c)(1), (2) Date Jan. 7, 2022,
PCT Pub. No. WO2021/007141, PCT Pub. Date Jan. 14, 2021.
Claims priority of provisional application 62/871,838, filed on Jul. 9, 2019.
Claims priority of application No. 19195787 (EP), filed on Sep. 6, 2019.
Prior Publication US 2022/0267247 A1, Aug. 25, 2022
Int. Cl. C07C 67/293 (2006.01); C07B 53/00 (2006.01)
CPC C07C 67/293 (2013.01) [C07B 53/00 (2013.01); C07B 2200/07 (2013.01)] 33 Claims
 
1. A process for the synthesis of a non-racemic cyclohexene compound of formula (I)

OG Complex Work Unit Chemistry
wherein
R1 is selected from C1-C8-alkyl, C3-C12-cycloalkyl, unsubstituted or substituted C6-C20-aryl and unsubstituted or substituted C3-C20-heteroaryl,
R2, R3, R4, R5, R6, R7, R8 and R9 are each independently selected from hydrogen, C1-C8-alkyl, C3-C6-cycloalkyl, unsubstituted or substituted C6-C20-aryl and unsubstituted or substituted C3-C20-heteroaryl, or R5 and R8 together form a bridging moiety selected from —O—, —OH2—, and —CH2—CH2— between the carbon atoms to which they are connected;
Y is OC(O)RA wherein RA is selected from C1-C8-alkyl, C3-C12-cycloalkyl, unsubstituted or substituted C6-C20-aryl, C6-C20-aryl-C1-C4-alkyl, di(C6-C20-aryl)-C1-C4-alkyl, unsubstituted or substituted C3-C20-heteroaryl, C1-C8-alkoxy, C3-C6-cycloalkyloxy, C6-C20-aryloxy, and NRBRB′, where RB and RB, are independently selected from hydrogen, C1-C8-alkyl, and C3-C12-cycloalkyl;
which process comprises reacting a compound of formula (II)

OG Complex Work Unit Chemistry
wherein R1, R2, R3 and Y have the same meaning as in formula (I) with a compound of formula III,

OG Complex Work Unit Chemistry
wherein R4, R5, R6, R7, R8 and R9 have the same meaning as in formula (I);
in the presence of a catalyst comprising at least one m-valent metal cation Mm+ wherein the metal M is selected from Scandium (Sc), Yttrium (Y), Lanthanum (La), Cerium (Ce), Praseodymium (Pr), Neodymium (Nd), Promethium (Pm), Samarium (Sm), Europium (Eu), Gadolinium (Gd), Terbium (Tb), Dysprosium (Dy), Holmium (Ho), Erbium (Er), Thulium (Tm), Ytterbium (Yb), Lutetium (Lu), Gallium (Ga) and Indium (In), and m is an integer of 1, 2 or 3, and a chiral ligand of the formula (IV)

OG Complex Work Unit Chemistry
wherein R10a, R10b, R10c, R10d, R10a′, R10b′, R10c′ and R10d′ are each independently selected from hydrogen, C1-C8-alkyl, C3-C6-cycloalkyl, unsubstituted or substituted C6-C20-aryl, C6-C20-aryl-C1-C4-alkyl and unsubstituted or substituted C3-C20-heteroaryl, or two or more of R10a, R10b, R10c and R10d and/or two or more of R10a′, R10b′, R10c′ and R10d′ together form an unsubstituted or substituted ring selected from C3-C6-cycloalkyl, C6-C20-aryl and C3-C20-heteroaryl;
provided that at least one of R10a, R10b, R10c and R10d and at least one of R10a′, R10b′, R10c′ and R10d′ are not hydrogen;
R11a, R11b and R11c are each independently selected from hydrogen, halogen, cyano, C1-C8-alkyl, C1-C4-haloalkyl, C3-C6-cycloalkyl, unsubstituted or substituted C6-C20-aryl, unsubstituted or substituted C3-C20-heteroaryl, C1-C5-alkoxy, C3-C6-cycloalkyloxy, C6-C2O-aryloxy, C(O)—O—C1-C6-alkyl and O—C(O)—C1-C6-alkyl, and
Z and Z′ are the same or different and selected from —O—, —O—CH2—,

OG Complex Work Unit Chemistry
wherein RC is selected from C1-C8-alkyl, C3-C8-cycloalkyl, C1-C8-haloalkyl, and unsubstituted or substituted C6-C13 aryl.