Enantioselective Synthesis of Medium-Sized-Ring Lactones via Iridium-Catalyzed Z-Retentive Asymmetric Allylic Substitution Reaction

Abstract

Medium-sized rings are important structural units, but their synthesis, especially in a highly enantioselective manner, has been a great challenge. Herein we report an enantioselective synthesis of medium-sized-ring lactones by an iridium-catalyzed Z-retentive asymmetric allylic substitution reaction. The reaction features mild conditions and a broad substrate scope. Various eight- to 11-membered-ring lactones can be afforded in moderate to excellent yields (up to 88%) and excellent enantioselectivity (up to 99% ee). The utilization of both Z-allyl precursors and an Ir catalyst is critical for the medium-sized-ring formation.

I2/CF3CO2Ag-mediated iodolactonization of various allenoic acids to access versatile 6- to 9-membered ring vinylic iodolactones

“…5 Owing to their structural diversity and unique biological activities, synthetic protocols of medium-sized lactones always attract the attention of medicinal chemists. 6 In contrast to the synthesis of 5-to 6-membered ring lactones, the efficient construction of mediumsized lactones remains a formidable challenge due to their inherent entropic factors and unfavorable transannular interactions. 6c Over the past decade, numerous synthetic strategies have been applied to prepare medium-sized lactones, including intramolecular esterification of hydroxycarboxylic acids, 1b intramolecular carbonyl hydroacylation of benzaldehydes, 7 metal-catalyzed cycloisomerization of alkynoic acids, 8 organocatalyzed halolactonization of olefinic acids, 9 bond-cleaving/ ring-expansion of oxindoles with zwitterion precursors 10 and so on.…”

Simultaneous Dual Cu/Ir Catalysis: Stereodivergent Synthesis of Chiral β-Lactams with Adjacent Tertiary/Quaternary/Tertiary Stereocenters

“…Asymmetric Ir­(I)-catalyzed allylic alkylation reactions have attracted significant attention in recent years due to their high regio- and enantioselectivity and are a most versatile and powerful method to construct C–C and C-heteroatom bonds. − Generally, amine or enolate formed by deprotonation of carbonyl precursors has been used as nucleophiles to produce chiral, branched products (Scheme a). − Application of prochiral nucleophiles in these reactions would produce vicinal chiral stereocenters, but the stereochemical control of reactions with a single Ir­(I) catalyst is difficult. The introduction of a second catalyst with the aim of catalyzing the generation of a chiral nucleophile which could participate this Ir­(I)-catalyzed substitution is an effective but challenging solution. − Carreira and co-workers developed the first dual enamine catalysis and Ir­(I)-catalyzed allylic substitution to provide a stereodivergent access to four stereoisomers (Scheme b) .…”

Benzo‐fused Nitrogen Heterocycles by Asymmetric Ring Expansion and Stereochemically Retentive Re‐contraction of Cyclic Ureas

“…[1,2] The synthesis of these heterocycles in enantiopure form is therefore a key target, and can be particularly challenging for medium rings. [3,4] Existing approaches to this class of compound include the iridium catalyzed enantioselective synthesis of indole-annulated medium rings via an allylic dearomatization/retro-Mannich/ hydrolysis cascade, [5,6] palladium catalyzed [5+2] cycloaddition of vinyl ethylene carbonates with α-diazoketones, [7] and enantioselective ring expansion of strained rings. [8] Shibata et al demonstrated an asymmetric synthesis of CF 3 -substituted nine-membered heterocycles by Pd-catalyzed decarboxylative ring expansion strategy, [9] and the enantioselec-tive construction of medium ring bridged biaryls is noteworthy.…”