Enantioselective Synthesis of Acyclic α‐Quaternary Carboxylic Acid Derivatives through Iridium‐Catalyzed Allylic Alkylation

Abstract

The first highly enantioselective iridium-catalyzed allylic alkylation providing access to products bearing an allylic all-carbon quaternary stereogenic center has been developed. The reaction utilizes a masked acyl cyanide (MAC) reagent, which enables the one-pot preparation of α-quaternary carboxylic acids, esters, and amides with a high degree of enantioselectivity. The utility of these products is further explored via a series of diverse product transformations.

Acyclic Quaternary Carbon Stereocenters via Enantioselective Transition Metal Catalysis

“…130 Very recently in 2017, these conditions were adapted to the use of masked acyl cyanide pronucleophiles. 131 The iridium catalyst modified by Carreira’s phosphoramidite ligand ( S )- XXXVIII was used in combination with triethyl borane, which was required to promote ionization of the trisubstituted allylic carbonate.…”

Palladium-Catalyzed Asymmetric Allylic Alkylation Strategies for the Synthesis of Acyclic Tetrasubstituted Stereocenters

“…The branch-selective Ir-AAA of trisubstituted cinnamyl electrophiles was demonstrated by the Stoltz group (Scheme 72). 66 In this reaction, acyl anion equivalent 205 is used to allow for easy access to -aryl--vinyl carbonyl compounds 207. This method demonstrates a new landmark in Ir-AAA, as more highly substituted electrophiles 206 have proven difficult in Ir-AAA.…”

Enantioselective Synthesis of Tertiary Allylic Fluorides by Iridium‐Catalyzed Allylic Fluoroalkylation

“…For example, malononitriles bearing methyl ( 2 g ), allyl ( 2 h ), and methoxymethyl ether ( 2 i ) substituents at the nucleophilic carbon reacted in the presence of triethylamine and catalyst C2 to provide allylic fluorides 3 ag , 3 ah , and 3 ai in uniformly high yields and high enantioselectivities. Product 3 ai is particularly valuable because its precursor ( 2 i ) is synthetically equivalent to a cyano acyl anion . Methyl Meldrum's acid ( 2 j ), which is less nucleophilic than acyclic malonic esters possessing comparable steric properties, underwent allylic fluoroalkylation to form product 3 aj in 66 % yield and 89:11 er, and the conjugate base of fluorobis(phenylsulfonyl)methane reacted to provide allylic fluoride 3 ak in acceptable yield and excellent enantioselectivity…”