US 11,053,209 B2
Highly efficient synthesis of z-macrocycles using stereoretentive, ruthenium-based metathesis catalysts
Tonia S. Ahmed, Pasadena, CA (US); and Robert H. Grubbs, South Pasadena, CA (US)
Assigned to CALIFORNIA INSTITUTE OF TECHNOLOGY, Pasadena, CA (US)
Appl. No. 16/611,329
Filed by CALIFORNIA INSTITUTE OF TECHNOLOGY, Pasadena, CA (US)
PCT Filed Apr. 24, 2018, PCT No. PCT/US2018/029106
§ 371(c)(1), (2) Date Nov. 6, 2019,
PCT Pub. No. WO2018/208501, PCT Pub. Date Nov. 15, 2018.
Claims priority of provisional application 62/503,155, filed on May 8, 2017.
Claims priority of provisional application 62/521,647, filed on Jun. 19, 2017.
Prior Publication US 2020/0102285 A1, Apr. 2, 2020
Int. Cl. C07D 313/00 (2006.01); B01J 31/22 (2006.01)
CPC C07D 313/00 (2013.01) [B01J 31/226 (2013.01); B01J 31/2273 (2013.01); B01J 31/2291 (2013.01); B01J 2231/543 (2013.01); B01J 2531/821 (2013.01)] 10 Claims
OG exemplary drawing
 
1. A method for producing at least one Z-macrocyclic product represented by Formula (VI):

OG Complex Work Unit Chemistry
wherein:
n is 1, 2, 3, or 4; m is 4, 5, 6, or 7; and the Z-macrocyclic product of Formula (VI) is a twelve, thirteen, fourteen, fifteen, sixteen, or seventeen-membered ring with a Z-selectivity of 95, or 98, or 99; comprising:
subjecting a diene substrate bearing a Z-olefin moiety represented by Formula (III):

OG Complex Work Unit Chemistry
wherein:
R′ is methyl, ethyl, or propyl; n is 1, 2, 3, or 4; and m is 4, 5, 6, or 7;
to a macrocyclic ring-closing metathesis reaction in the presence of a stereoretentive Ru-based catalyst represented by Formula (I):

OG Complex Work Unit Chemistry
wherein:
R is iso-propyl and R0 is nil;
R1, R5, R6, and R10, are iso-propyl;
R2, R3, R4, R7, R8, R9, R11, R12, R13, and R14 are H;
R15, R16, R17, and R18 are H;
X2 and X3 are H;
X1 and X4 are chloro; and
Y is oxygen.