title: Direct generation of acyclic polypropionate stereopolyads via double diastereo- and enantioselective iridium-catalyzed crotylation of 1,3-diols: beyond stepwise carbonyl addition in polyketide construction.
abstract: Under the conditions of transfer hydrogenation employing the cyclometalated iridium catalyst (R)-I derived from [Ir(cod)Cl](2), allyl acetate, 4-cyano-3-nitrobenzoic acid, and the chiral phosphine ligand (R)-SEGPHOS, α-methylallyl acetate engages 1,3-propanediol (1a) and 2-methyl-1,3-propanediol (1b) in double carbonyl crotylation from the alcohol oxidation level to deliver the C(2)-symmetric and pseudo-C(2)-symmetric stereopolyads 2a and 3a, respectively, with exceptional control of anti-diastereoselectivity and enantioselectivity. Notably, the polypropionate stereopentad 3a is formed predominantly as 1 of 16 possible stereoisomers. Desymmetrization of 3a is readily achieved upon iodoetherification to form pyran 4. The direct generation of 3a enables a dramatically simplified approach to previously prepared polypropionate substructures, as demonstrated by the synthesis of C19-C27 of rifamycin S (eight steps, originally prepared in 26 steps) and C19-C25 of scytophycin C (eight steps, originally prepared in 15 steps). The present transfer hydrogenation protocol represents an alternative to chiral auxiliaries, chiral reagents, and premetalated nucleophiles in polyketide construction.
authors: Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, Texas 78712, United States.
authors: Xin
authors: X
authors: Gao
authors: Hoon
authors: H
authors: Han
authors: Michael J
authors: MJ
authors: Krische
mesh_terms: D002384:Catalysis; D006865:Hydrogenation; D007495:Iridium / Q000737:chemistry*; D009579:Nitrobenzoates / Q000737:chemistry*; D061065:Polyketides / Q000138:chemical synthesis* / Q000737:chemistry; D011422:Propionates / Q000138:chemical synthesis / Q000737:chemistry*; D011409:Propylene Glycols / Q000737:chemistry*; D012294:Rifamycins / Q000138:chemical synthesis; D013237:Stereoisomerism
chemical_list: D009579:Nitrobenzoates; D061065:Polyketides; D011422:Propionates; D011409:Propylene Glycols; D012294:Rifamycins; D007495:Iridium; C041787:1,3-propanediol; C040770:3-nitrobenzoic acid; C029658:propionic acid; C437090:2-methyl-1,3-propanediol; C032779:rifamycin S