α-Hydroxy ketones as useful templates in asymmetric reactions

Abstract

Approaching the Nature's efficiency in controlling both reactivity and stereoselectivity of organic reactions by means of a catalyst species remains a formidable challenge for chemists to face. Despite impressive advances in the design of novel catalysts and activation modes, current catalytic and asymmetric methodologies rarely meet desirable standards of robustness, substrate scope, and selectivity altogether. One trick to improve catalyst behaviour is to identify adequate substrate template-catalyst combinations so that optimum performance of the reaction system could be achieved. During the last couple of years α-hydroxy ketones, and most particularly α'-hydroxy enones, have emerged as useful templates with applications in a number of metal-catalyzed as well as organocatalyzed C-C and C-X bond-forming stereoselective reactions. The first review of these accomplishments is presented here along with a brief historical introduction.

Base‐Free Asymmetric Transfer Hydrogenation of 1,2‐Di‐ and Monoketones Catalyzed by a (NH)2P2‐Macrocyclic Iron(II) Hydride

“…[2] However,t he base additives that are required to activate the precatalyst [3] tend to limit the reaction scope.A ne minent example are ahydroxy ketones,f or example,b enzoin (A)o r, more generically,a cyloins (Figure 1), whose base-labile stereocenter easily racemizes upon heating or in basic media, [4] making the asymmetric hemihydrogenation of 1,2-diketones aformidable challenge. [5] Enantiomerically pure acyloins are frequent structural subunits in natural products [6] and bioactive molecules, [7] and act as chiral templates and building blocks [8] thanks to the combination of the highly directing hydroxy group with the easily functionalized prostereogenic carbonyl. [9] Their synthesis has been accomplished by an umber of chemical and biocatalytic [7] methods such as the stoichiometric [10] and catalytic [11] oxidation of enolates or enol ethers,a lkene ketohydroxylation, [9] oxidative kinetic resolution, [12] dynamic kinetic resolution, [13] monooxidation of 1,2-diols, [14] benzoin condensation, [15] Friedel-Crafts reactions, [16] enzymatic reductions, [17] and asymmetric hydrosilylation with chiral frustrated Lewis pairs.…”

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The hydride isonitrile complex [FeH(CNCEt 3 )-(1a)]BF 4 (2)c ontaining ac hiral P 2 (NH) 2 macrocycle (1a), in the presence of 2-propanol as hydrogen donor,catalyzesthe base-free asymmetric transfer hydrogenation (ATH) of prostereogenic ketones to alcohols and the hemihydrogenation of benzils to benzoins,w hichc ontain ab ase-labile stereocenter. [5] Enantiomerically pure acyloins are frequent structural subunits in natural products [6] and bioactive molecules, [7] and act as chiral templates and building blocks [8] thanks to the combination of the highly directing hydroxy group with the easily functionalized prostereogenic carbonyl. [2] However,t he base additives that are required to activate the precatalyst [3] tend to limit the reaction scope.A ne minent example are ahydroxy ketones,f or example,b enzoin (A)o r, more generically,a cyloins (Figure 1), whose base-labile stereocenter easily racemizes upon heating or in basic media, [4] making the asymmetric hemihydrogenation of 1,2-diketones aformidable challenge.

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7.07 α-Oxygenation of Carbonyl Compounds

“…In the rhodium-catalyzed synthesis of furanones from b-ketoesters, DIB was utilized to form an intermediate iodonium ylide, which cyclized to the corresponding 2-substituted heterocycle. 157 Iodosylbenzene mediates the transformation of tricarbonyl compounds into fused dihydrofurans via a [1,5]-oxidative cyclization. 158 In 2010, Ishihara reported a highly enantioselective oxidative cycloetherification using hydrogen peroxide as the stoichiometric oxidant and a chiral quaternary ammonium iodide catalyst as the source of asymmetric induction (Scheme 56).…”

“…1 The a-hydroxycarbonyl group is also present in many types of natural products, including polyketides, terpenoids, and alkaloids. The asymmetric synthesis of aoxygenated carbonyl compounds is of major interest in the pharmaceutical industry, as many antibiotics and other biologically active compounds contain a-hydroxycarbonyl fragments ( Figure 1).…”

Dimethylzinc-Mediated Addition of Phenylacetylene to α-Diketones Catalyzed by Chiral Perhydro-1,3-benzoxazines

“…2 In addition, they can be used for the further formation of many other important structures as amino alcohols, diols or α-hydroxy ethers. 3 Various methods have been developed for the enantioselective synthesis of α-hydroxy ketones including oxidation of enolates 4 and enol ethers, 5 the direct asymmetric α-oxygenation of ketones in the presence of chiral catalyst, 6 the asymmetric mono-oxidation of the correspondent 1,2-diols, 7 the ketohydroxylation of olefins, 8 the oxidative kinetic resolution of racemic α-hydroxy ketones, 9 the asymmetric hydrogenation of α-diketones, 10 the traditional benzoin condensation carried out stereoselectively by means of optically active catalysts 11 as well as different biocatalytic strategies.…”