Asymmetric vinylogous aldol addition of alkylidene oxindoles on trifluoromethyl-α,β-unsaturated ketones

Abstract

The vinylogous aldol addition of alkylidene oxindole with 1-trifluoromethyl-3-alkylidene-propan-2-ones was developed. The reaction, provides straightforward access to enantioenriched trifluoromethylated allylic alcohols.

New Developments of the Principle of Vinylogy as Applied to π-Extended Enolate-Type Donor Systems

“…The efficacy of alkylidene oxindoles in additions to vinyl trifluoromethyl ketones was also demonstrated by Bencivenni et al in a recent study that aimed at producing enantioenriched fluorinated allylic alcohols as precursors of molecular entities of biological interest ( Scheme 205 , eq 2). 524 In this work, the authors had to face the challenging issues of chemo- and regioselectivity in addition to the stereoselectivity. In fact, when trifluoromethyl vinyl ketones of type 805 are used, both the 1,2- and 1,4-addition products can be in principle formed, and the pronucleophilic γ and γ′ positions within the oxindole 800 could compete with each other leading to a mixture of E / Z alkenes.…”

“…The efficacy of alkylidene oxindoles in additions to vinyl trifluoromethyl ketones was also demonstrated by Bencivenni et al in a recent study that aimed at producing enantioenriched fluorinated allylic alcohols as precursors of molecular entities of biological interest (Scheme , eq 2) . In this work, the authors had to face the challenging issues of chemo- and regioselectivity in addition to the stereoselectivity.…”

Catalytic Diastereo- and Enantioselective Synthesis of Tertiary Trifluoromethyl Carbinols through a Vinylogous Aldol Reaction of Alkylidenepyrazolones with Trifluoromethyl Ketones

“…Later, Han and Paidamoyo reported the vinylogous aldol reaction of 3-methylcyclohex-2-en-1-one to a wide range of trifluoromethylarylketones with very good results using a diamine-sulfonamide organocatalyst . Also Bencivenni’s group presented the vinylogous aldol addition of alkylidene oxindoles to trifluoromethyl-α,β-unsaturated ketones obtaining chiral trifluoromethylated allylic alcohols in moderate yields (48–88% yield) and with excellent enantioselectivities (up to 96% ee). Moreover, several examples of an enantioselective vinylogous aldol-lactonization cascade reaction have been reported in the literature for the preparation of chiral unsaturated δ-lactones bearing a trifluoromethyl group .…”

One-pot two-step chemoenzymatic deracemization of allylic alcohols using laccases and alcohol dehydrogenases

“…As a consequence, several chemical methodologies have been described to synthesize these compounds in a chiral fashion [6]. Recent examples involve the (stereoselective) formation of C-C bonds, such as the alkenylation of aldehydes [7], the coupling of alcohols and alkynes under redox neutral conditions [8], the aldol addition on α,β-unsaturated ketones [9], the alkyl addition on α,β-unsaturated aldehydes [10], and the Stille coupling reaction [11].…”