All-catalytic, efficient, and asymmetric synthesis of alpha,omega-diheterofunctional reduced polypropionates via "one-pot" Zr-catalyzed asymmetric carboalumination-Pd-catalyzed cross-coupling tandem process.
A highly efficient method for the synthesis of stereochemically pure (>/=99% ee and >50/1 dr) alpha,omega-diheterofunctional reduced polypropionates has been developed. The essential features of the method are represented by the conversion of inexpensive styrene into 2-methyl-4-phenyl-1-pentanol (1) in 50% yield over two steps from styrene via Zr-catalyzed asymmetric carboalumination (ZACA) reaction in the presence of (NMI)2ZrCl2 and Pd-catalyzed vinylation of the in situ generated isoalkylalanes in the presence of Zn(OTf)2 and a catalytic amount of Pd(DPEphos)Cl2. This ZACA-Pd-catalyzed vinylation may be repeated as needed without purification. After the final ZACA reaction, oxidation with O2 provides alpha-hydroxy-omega-phenyl reduced polypropionates, which can be fully or partially purified by chromatography. After acetylation, Ru-catalyzed oxidative cleavage of the Ph ring, and reduction with BH3.THF, the second chromatographic purification provides stereoisomerically pure alpha,omega-diheterofunctional reduced polypropionates (e.g., 9 and 11) that can be further converted to key intermediates 6 and 7 for the synthesis of ionomycin (4) and borrelidin (5), respectively, by known reactions.
Novak
Tibor
T
Herbert C. Brown Laboratories of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, USA.
Tan
Ze
Z
Liang
Bo
B
Negishi
Ei-Ichi
E
D000418:Albumins / Q000737:chemistry; D002384:Catalysis; D005233:Fatty Alcohols / Q000138:chemical synthesis; D015759:Ionomycin / Q000138:chemical synthesis; D010084:Oxidation-Reduction; D010165:Palladium / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis*; D011422:Propionates / Q000138:chemical synthesis*; D020058:Styrene / Q000737:chemistry; D015040:Zirconium / Q000737:chemistry*
D000418:Albumins; D005233:Fatty Alcohols; D011108:Polymers; D011422:Propionates; D020058:Styrene; D015759:Ionomycin; D010165:Palladium; C005066:borrelidin; D015040:Zirconium