Trimethyl Orthoacetate and Ethylene Glycol Mono‐Vinyl Ether as Enolate Surrogates in Enantioselective Iridium‐Catalyzed Allylation

Abstract

Trimethyl orthoacetate and ethylene glycol mono‐vinyl ether are employed in iridium‐catalyzed enantioselective allylation reactions. The method documented enables their convenient use as surrogates for silyl ketene acetals and silyl enol ethers to prepare γ,δ‐unsaturated esters and protected aldehydes with excellent enantioselectivity. The utility of this novel method has been demonstrated by its implementation in a formal enantioselective synthesis of the meroterpenoid (+)‐conicol.

Iridium-Catalyzed Asymmetric Allylic Substitution Reactions

“…Recently, the Carreira group disclosed that orthoacetate 179 could act as a commercially available surrogate for acetate enolates to participate in iridium-catalyzed allylic alkylation, providing the γ,δ-unsaturated esters 181 in good yields and excellent enantioselectivity (Scheme 96). 167 In this reaction, allylic carbonates 180 were used instead of the frequently used allylic alcohols to avoid the formation of mixed ketene acetals. The Lewis acid additives had a dramatic influence on the outcomes.…”

Applications of alkyl orthoesters as valuable substrates in organic transformations, focusing on reaction media

“…Notably, the meroterpenoid (+)-conicol has been synthesized through employment of this new procedure in a formal enantioselective synthesis. 387 Brodzka and co-workers probed the enzymatic kinetic resolution (EKR) of Novozym 435 as a biocatalyst for the synthesis of enantiomerically pure carboxylic acid esters (456) via the esterication of racemic 3-phenyl-4-pentenoic acid (454) with trialkyl orthoesters (4,5,6,62,102,323,380,444,455) as alkoxy group donors in toluene at 40 C (Scheme 132). Based on the resulting data, trialkyl orthoesters including bulky alkyl groups, such as trialkyl orthobenzoate, obtained excellent results for both yield and enantioselectivity (50% yield, >99% ee).…”

“…Notably, the meroterpenoid (+)-conicol has been synthesized through employment of this new procedure in a formal enantioselective synthesis. 387 …”

Palladium-catalyzed enantioselective (2-naphthyl)methylation of azaarylmethyl amines

“…We envisioned that nucleophilic attack on η 3 -benzyl-type intermediates could be potentially useful in the construction of enantioenriched azaarylmethyl amines. Compared with Pd-catalyzed asymmetric allylic alkylations, [24][25][26][27][28][29][30][31][32][33][34][35] enantioselective benzylic alkylations are far less common. 36 This is likely due to the greater difficulty forming the initial arene intermediate, (LG-CH 2 C 6 H 5 )-Pd(0), and the subsequent oxidative ionization of the leaving group with concomitant disruption of aromaticity.…”