Selective Synthesis of Unsymmetrical Aliphatic Acyloins through Oxidation of Iridium Enolates

Abstract

The first method to access unsymmetrical aliphatic acyloins is presented. The method relies on a fast 1,3-hydride shift mediated by an Ir complex in allylic alcohols followed by oxidation with TEMPO . The direct conversion of allylic alcohols into acyloins is achieved in a one-pot procedure. Further functionalization of the Cα' of the α-amino-oxylated ketone products gives access to highly functionalized unsymmetrical aliphatic ketones, which further highlights the utility of this transformation.

An umpolung strategy to react catalytic enols with nucleophiles

“…Several by-products may be formed from the allylic alcohol substrates 1, including unsubstituted ketone 3, and also enone 4. Furthermore, other nucleophiles such as water could , where common solvents previously used in related reactions were tested [35][36][37][38][39][40][41] . When either acetone or THF was used ( Table 1, entries 1 and 2), 2a was formed in moderate yield (up to 43%) together with byproducts 3-6 in yields ranging from 6 to 12%.…”

“…Allylic alcohols have been proven to be a very useful class of compounds as ketone synthons during the last decades 32,33 . Our group has reported the use of allylic alcohols as enolate equivalents for the preparation of α-functionalized carbonyl compounds as single constitutional isomers [34][35][36][37][38][39][40][41] . This approach relies on the generation of iridium enolates as catalytic intermediates through 1,3-hydrogen transfer, and the in situ reaction of these intermediates with a variety of heteroatomic electrophiles, including halogen and oxygen-based electrophilic species.…”

Transition metal-catalyzed alkene isomerization as an enabling technology in tandem, sequential and domino processes

“…81 Acyloins (57e) have been prepared following the same approach using an oxoammonium tetrafluoroborate salt derived from TEMPO. 82 Finally, an ingenious variant based on an isomerization/ umpolung functionalization strategy has been published by the Martín-Matute group. 83 The combination of the appropriate iodine(III) reagent in methanol provided access to the targeted a-alkoxy ketones.…”

Stereospecific Isomerization of Allylic Halides via Ion Pairs with Induced Noncovalent Chirality

“…These species could be harnessed and applied in further transformations, opening up new synthetic opportunities. Our group has shown that in the presence of a range of different electrophiles and even nucleophiles, α-substituted ketones are formed as single constitutional isomers. , …”