A-Hydroxy enones

As discussed in Section 12.2.2, homoenolates can be accessed from a-hydroxy-enones, and an asymmetric synthesis of cyclopentenes has been achieved using this strategy with enones (Scheme 12.42) [15]. 

The preparation of a-hydroxy carbonyl compounds has been accomplished by the oxidation of enolates using both oxygen6 and MoC PyHMPA-(MoOPh).7 Acyl anion equivalents offer another route to this useful class of compounds. The procedure presented here for the synthesis of 6-hydroxy-3,5,5-tr1methyl-2-cyclohexen-l-one illustrates the use of MCPBA oxidation of an enol silyl ether as a method for obtaining an a-hydroxy enone. The procedure is a scaleup of a published synthesis. ... 

Cyclization of Divinyi Ketones from a -Hydroxy Enones... 

Cyclization of Divinyl Ketones from (-Substituted Enones 6.332 Cyclization Divinyl Ketones from a -Hydroxy Enones... 

High levels of regio- and stereoselectivity were observed in metal-catalyzed 1,3-DC of acyclic nitrones with a -hydroxy enones. The reaction probably occurs through the formation of reactive 1,4-metal-chelated intermediates. The remarkable diastereo- and enantiocontrol could be obtained through two complementary approaches by using a camphor-derived a -hydroxy enone in combination with Cu(OTf)2 or an achiral enone such as 81 in combination with the bis(oxazoline)-Cu(II) catalyst 83. At the end, the hydroxylated auxiUaiy could be easily removed. For example, treatment with periodic acid released a carboxylic moiety as in 86 and 87 <05AG(E)6187>. 

Grieco and coworkers19 employed the trimethyliodosilane/hexamethyldisilazane (HMDS) combination, first introduced by Miller and McKean20, to prepare dienol silyl ether 2 (equation 13). This enol silyl ether was converted via the Rubottom reaction to the sensitive a-hydroxy enone A ring of Quassimarin, 3. 

Carbonyl compounds from a-amino nitriles. A synthesis of a-hydroxy enones from the a-amino nitrile derivatives of enals starts from alkylation with aldehydes and the hydrolysis of the products. ... 

Hydroxy-4,6-diphenyl-2-pyridone, 456 a-Hydroxy enones, 100, 101 a-Hydroxy epoxides, 60-61 3-Hydroxy esters, 164, 536 Hydroxyindolines, 99... 

A series of a-hydroxy enones gave good results with a t-butyl BOX catalysts or its cyclopropyl analog [248]. 

The Pd-catalyzed reactions of a-heterosubstituted alkenylzincs containing alkoxy and thioalkoxy groups were developed with the goal of synthesizing heterosubstituted conjugated dienes for the Diels-Alder reaction (Scheme 56). The use of the parent aUcenyllithiums did not produce the desired dienes in detectable amounts. This reaction has been applied to the synthesis of steroidal a-hydroxy enones (Scheme 57). It should be noted that Zn has been shown to be decidedly superior to Sn as the countercation. 

In 2010, Huang and co-workers reported an AFC alkylation of indoles with P-aryl a -hydroxy enones catalyzed by a cooperative catalytic system involving an iron salt and a chiral phosphoric acid (Scheme 6.34). Good to excellent... 

Scheme 6.34 AFC alkylation of indoles with various P-aryl a -hydroxy enones reported by Huang.

For instance, an early example by Jorgensen relates to p,y-unsaturated a-ketoesters 169, which served as acceptors for indoles, furanes and electron-rich arenes [135]. The same catalyst system, a combination of Cu(OTf)2 and tert-butyl-substituted bisoxazoline 173, was employed by Palomo in the highly enantioselective addition of indoles and pyrroles to a -hydroxy enones 170 (Figures 8.11 and 12) [136]. 

More recently, Palomo and co workers reported the application of Cu(OTf)2/(13) for highly enantioselective addition of pyrroles and indoles to a -hydroxy enones [10]. The a -hydroxy enone substrate-Cu(OTf)2/(13) catalyst system provides for excellent enantioselectivities with a variety of P substituents. It is also noteworthy that remarkable increases in enantioselectivity were observed in Friedel-Crafts alkylations of indoles when reactions were conducted under refluxing conditions (Scheme 17.5). 

Cu(OTf)2/t-Bu-BOX (13)-catalyzed conjugate addition of carbamates to a -hydroxy enones has been demonstrated by Palomo and coworkers (Scheme 17.50) [69]. Conjugate additions of carbamates (235) to a -hydroxy enones (29) bearing aliphatic P-substituents proceed in moderate to good yield with excellent enantioselectivity. However, enones bearing -aryl substituents lack sufficient reactivity. The impact of the a -hydroxy enone template in this methodology bears mention, as an a,P-unsaturated oxazolidinone substrate is completely unreactive under identical conditions. 

In 2010, Xia, Huang and co-workers reported an iron-assisted chiral phosphoric acid catalyst for the Fridel-Crafts reaction between indole and 3-aryl a -hydroxy enones (Fig. 16) [70]. Due to the evidence from electron spray ionization mass spectrometry (ESI-MS) analysis for the presence of iron phosphate salt, an iron/ proton dual activation mechanism was proposed to account the observed reactivity/ selectivity trends. Addition of a third acid component, silver triflate, was shown to be beneficial for the enantioselectivity, presumably by exchanging chloride to the less coordinating triflate anion. 

Formation of Dienones and Furanones. Furanones are formed typically by treatment of a-hydroxy enones with acid the reaction is presumed to proceed via an acid-labile dienone, although no direct evidence for the existence of such an intermediate has been demonstrated. It haS been shown that a-hydroxy enones... 

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