Y-Hydroxyketones

Vinylsulfonates (24) undergo a facile intramolecular Diels-Alder reaction affording the exo-sultones (25) with excellent diastereo-selectivity. Oxidative desulfurisation of the sultones gives access to y-hydroxyketones and hence vinylsulfonyl chloride used to prepared (24) behaves as a ketone equivalent (951711). 

The conversion of the nitro gronp into a carbonyl can be accomplished by several alternative methods although the use of H2O2/K2CO3 appeared to be the most compatible to develop environment-friendly processes. As reported in Figure 2.10, the y-hydroxyketones could not be isolated, since they spontaneously cyclized to the corresponding lactols (39). 

In the reaction of y-hydroxyketones 453 or e-hydroxyketones" with DCC, cyclic products 454 are obtained resulting from intramolecular alkylation. 

Other examples The addition reaction of lithium enolates of ketones to 1,2-epoxides to afford the a-alkyl-y-hydroxyketones. (a) P. Crotti, V. D. Bussolo, L. Favero, M. Pineschi, M. Pasero, J. Org. Chem. 1996, 61, 9548-9552. The cross-aldol reactions between ketones and aldehydes, (b) S. Fuku-zawa, T. Tsuchimoto, T. Kanai, Bull. Chem. Soc. Jpn. 1994, 67, 2227-2232. 

Intramolecular dehydration of y-hydroxyketones.2 When y-hydroxy ketones are heated to about 150° with DCC, water is eliminated with formation of a cyclopropane ring. For example, 5-hydroxy-2-pentanone (1) is transformed into (3) in 80% yield. In the suggested mechanism, (2) is proposed as an intermediate. The reaction is noteworthy because dehydration is accompanied by formation of a carbon-carbon bond. 

Aminophosphonylation of a y-hydroxyketone leads to phosphonic analogues of a-methyl-homoserine, which can be cyclized to the 2-alkoxy-3-amino-l, 2-oxaphosphinane oxides (284) (Equation (18)) <93PS(81)17>. 

Several other examples of the reduction-cyclization of y-hydroxyketones have been reported <84JA5304, 87CAR(171)141, 89JOC610, 89X3139, 91HCA397, 92XL2557>. 

Silylated allenylcarbinols are readily cyclized to 2,3-disubstituted tetrahydrofurans <91SL869>. Tetrahydrofurans are also obtained when y-hydroxyketones are treated with silanes <89T3139>. 

Cyclic y -hydroxyketones from -cyanoketals via 7-iminoketals and y-diketones... 

Scheme 11.45 Rh(OAc)2 and chiral Lewis acid-catalyzed reaction to produce y-hydroxyketone with a tetrasubstituted carbon center [66b].

Michael-type reactions have been achieved with baker s yeast using trifluoroethanol as the co-substrate (Scheme 5.17). These transformations probably are related to the acyloin condensation in that it has been proposed that the trifluoroethanol is initially oxidized enzymically to the aldehyde, which is then converted to a reactive acyl anion that can add to the electrophilic enone in a conjugate manner. The a, -unsaturated ketones are good Michael acceptors, leading to the corresponding y-hydroxyketones (via the diketone intermediate) in moderate yields (26-40%) and good optical purities (e.e. = 79%). The absolute configurations of the products (16) were not determined. 

For the last two decades, the use of the platinum- or rhodium-catalyzed intramolecular hydrosilylation/Tamao-Fleming oxidation sequence has been well recognized as a powerful method for the stereoselective synthesis of various structurally diverse alcohols (1,3-diols, 2-alkoxy-l,3-diols, and 2-aminoalcohols) and ketone derivatives (/3-hydroxyketones, y-hydroxyketones, o, /3-dihydroxyketones, and a,y-dihydroxyketones) from simple and readily available starting materials such as substituted allyl or propargyl alcohols and their homologues (4,177). Selected applications are presented in equations (24-26). 

Addition of an aUcyllithium to the aldehyde of 132, followed by cation exchange to the potassium alkoxide, led to 1,5-Brook rearrangement. The resulting potassium dithiane 133 was allylated, providing masked y-hydroxyketone 134 in good overall yield. 

In order to expand the synthetic applicability of the methodology, Hu et al. decided to employ Michael acceptors as other type of electrophiles. They developed a three-component reaction between an aryl diazo compound, H O, and an enone, for the generation of y-hydroxyketones 126 bearing a quaternary carbon stereocenter, catalyzed by the system Rhj(OAc) (2mol%)/chiral Lewis acid (30mol%) [165a], Different Lewis acids were tested as cocatalysts, but only the Sc-, Yb-, and Zn-based catalysts proved to be active. 

Cooperative catalysis in multi-component reactions highly enantioselective synthesis of y-hydroxyketones with a quaternary carbon stereocenter, (b) X. Han, M. Gan, H. Qin, J. Ji, X. Zhang, L. Jiang, W. Hu, Synlett 2011, 1717-1722. Trapping of oxonium ylides with Michael acceptors highly diastereoselective three-component reactions of diazo compounds with alcohols and ben-zylidene Meldrum s acids/4-oxo-enoates. 

---