Ir-Catalyzed Asymmetric Cascade Allylation/Spiroketalization Reaction for Stereoselective Synthesis of Oxazoline-Spiroketals

Abstract

An asymmetric cascade allylation/spiroketalization reaction between 2-(1-hydroxyallyl)phenols and 5-methyleneoxazolines is accomplished by using a chiral Ir(I) catalyst derived from commercially available iridium precursor and the Carreira ligand. This protocol furnishes a class of structurally novel and unique oxazoline-spiroketals in up to 86% yield, >99% ee and >20:1 dr. Moreover, control experiments reveal that 4,4-disubstitution on 5-methyleneoxazolines is necessary to avoid the aromatization and for the spiroketalization to occur. On the basis of this, a plausible reaction mechanism is illustrated.

Iridium/Acid Dual-Catalyzed Enantioselective Aza-ene-type Allylic Alkylation of Nitro Ketene Aminals with Racemic Allylic Alcohols

“…During the past decades, iridium-catalyzed asymmetric allylic alkylations have emerged as a powerful tool for the construction of carbon–carbon and carbon–heteroatom bonds in organic synthesis. , In 2019, Carreira and co-workers developed morpholine ketene aminal as a surrogate for amide enolates in Ir-catalyzed asymmetric allylic alkylations (Scheme a), affording γ,δ-unsaturated β-substituted morpholine amides with excellent enantioselectivities. , Inspired by this elegant work, as well as in conjunction with our continuing interest in the Ir-catalyzed asymmetric allylic alkylations, we envisaged that nitro ketene aminal could serve as a valid nucleophilic reagent to trap electrophilic π-allyl-Ir species (Scheme b), and introducing the nitro group could inhibit the hydrolysis of ketene aminal, thus synthesizing α-allylic nitro ketene aminal derivatives. While this reaction design is theoretically feasible, there are still several inherent challenges.…”

Enantioselective synthesis of spiro-N,O-ketals via iridium and Brønsted acid co-catalyzed asymmetric formal [4+2] cycloaddition

“…9,11 However, applying such a strategy to the synthesis of chiral spiro-heterocycles remains challenging, and reports of highly enantioselective synthesis of N -unsubstituted chiral spiro- N , O -ketals are scant. 12…”

Enantioselective Ir-Catalyzed Allyl Alkylation/Semipinacol Rearrangement

“…Following the seminal achievements of Takeuchi and Helmchen, iridium catalysts are now widely employed by Hartwig, Carreira, and You et al in the allylic substitution reactions . Of particular interest is Carreira’s Ir­(I)-(P,olefin) catalyst that engages alkenes in the AAA transformations, including allyl–alkene coupling, AAA-aromatization, AAA-cyclization, and AAA-Schmidt rearrangements (Scheme b). Inspired by these achievements, we envision that the putative allyl-Ir intermediate is sufficiently electrophilic to induce enantioselective SPR of tertiary allylic alcohols.…”