Iridium-Catalyzed Allylation of Chiral β-Stereogenic Alcohols: Bypassing Discrete Formation of Epimerizable Aldehydes

Abstract

The cyclometallated π-allyliridium 3,4-dinitro-C,O-benzoate complex modified by (R)- or (S)-Cl,MeO-BIPHEP promotes the transfer hydrogenative coupling of allyl acetate to β-stereogenic alcohols with good to excellent levels of catalyst-directed diastereoselectivity to furnish homoallylic alcohols. Remote electronic effects of the C,O-benzoate of the catalyst play a critical role in suppressing epimerization of the transient α-stereogenic aldehyde.

Catalytic Enantioselective CH Functionalization of Alcohols by Redox‐Triggered Carbonyl Addition: Borrowing Hydrogen, Returning Carbon

“…Here, the reaction products were isolated as single enantiomers, as the minor enantiomer of the mono‐adduct was transformed into the meso stereoisomer 17. The enhanced efficiency observed for iridium complexes that were purified by conventional flash column chromatography on silica gel availed further capabilities, such as highly diastereoselective CH allylations of chiral β‐stereogenic alcohols 15e. This method bypasses the discrete generation of configurationally labile chiral α‐stereogenic aldehydes, which often cannot be stored or subjected to column chromatography on silica gel without erosion of enantiomeric purity 18.…”

“…For example, in the reaction of primary alcohols with α‐methyl allyl acetate to form CH crotylation products (Scheme ),19a,b the kinetic selectivity that is observed in the generation of the ( E )‐σ‐crotyliridium intermediate, which reacts stereospecifically to deliver the anti ‐diastereomer, is preserved when the rate of carbonyl addition is accelerated with respect to isomerization of the σ‐crotyliridium intermediate to the Z isomer, which reacts stereospecifically to form the syn ‐diastereomer. Indicative of enhanced Lewis acidity at the iridium center, longer CIr, OIr, and PIr bonds are evident in the more electron‐deficient C , O ‐benzoate complexes, as determined by single‐crystal X‐ray diffraction analysis 15e. Exploiting these subtle effects, a double alcohol CH crotylation of 2‐methyl‐1,3‐propane diol to form the indicated pseudo‐ C 2 ‐symmetric polypropionate stereoquintet was developed 19c.…”

Asymmetric Iridium-Catalyzed C–C Coupling of Chiral Diols via Site-Selective Redox-Triggered Carbonyl Addition

“…Interestingly, both catalytic efficiency and stereoselectivity is dramatically influenced by remote substituents at the 4-position of the C,O -benzoate moiety. As suggested by single crystal X-ray diffraction data of a series of π-allyliridium C,O -benzoate complexes (Scheme 3) [53], more electron deficient C,O -benzoate ligands enhance Lewis acidity at iridium, which may accelerate turnover limiting carbonyl addition with respect to protonolytic cleavage of the π-allyl and other competing processes.…”

“…These processes are redox-efficient as they merge alcohol oxidation and C-C bond construction events, bypassing discrete alcohol-to-aldehyde redox reactions, as well as manipulations required for the stoichiometric formation of premetalated reagents. One of the most useful processes based on this pattern of reactivity is the enantioselective iridium catalyzed coupling of primary alcohols with allyl acetate to form secondary homoallylic alcohols (Scheme 1) [49, 50, 51, 52, 53]. Such primary alcohol C -allylations have been applied to the syntheses of diverse polyketide natural products, resulting in the most concise routes reported, to date [54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64].…”

Katalytische enantioselektive C‐H‐Funktionalisierung von Alkoholen durch redoxgesteuerte Addition an die Carbonylgruppe: Wasserstoff‐Ausleihe und Kohlenstoff‐Rückgabe

“…Die beobachtete höhere Aktivität von Iridiumkomplexen, die mittels herkömmlicher Flash‐Kieselgelchromatographie gereinigt wurden, ermöglichte erweiterte Anwendungen, z. B. in der diastereoselektiven C‐H‐Allylierung von chiralen β‐stereogenen Alkoholen 15e. Mit diesem Verfahren wird die separate Bildung von konfigurationslabilen chiralen α‐stereogenen Aldehyden umgangen, die oftmals nicht ohne Beeinträchtigung der Enantiomerenreinheit aufbewahrt oder der Kieselgelchromatographie unterzogen werden können 18.…”