A-Hydroxyketones synthesis

DAVIDSON Oxazole Synthesis Synthesis of Iriaryl oxazoles from a-hydroxyketones (benzoins)... 

A formal total synthesis of the prostaglandin involved unmasking of an isoxazoline ring by hydrogenation over W-2 Raney Ni/BCl3/MeOH, H2O to reveal a -hydroxyketone. It was necessary in this case to deactivate the Raney... 

Hydroperoxides, as optically active oxidizing agents 289-291 Hydrosulphonylation 172 /J-Hydroxyacids 619 a-Hydroxyaldehydes, synthesis of 330 a-Hydroxyalkyl acrylates, chiral 329 j -Hydroxycarboxylic esters, chiral 329 3-Hydroxycycloalkenes, synthesis of 313 Hydroxycyclopentenones, synthesis of 310 -Hydroxyesters 619 synthesis of 616 Hydroxyketones 619, 636 Hydroxymethylation 767 a-Hydroxysulphones, synthesis of 176 / -Hydroxysulphones 638, 639 reactions of 637, 944 electrochemical 1036 synthesis of 636 y-Hydroxysulphones 627 synthesis of 783... 

Ishikawa s synthesis of ( )-0-methylkinamycin C (54) represents a distinct approach to the kinamycins that hinges on a key Diels-Alder reaction to establish the tetracyclic skeleton of the natural products. Additional key steps in the sequence include a substrate-directed dihydroxylation, substrate-directed reduction, and spontaneous epimerization of an a-hydroxyketone intermediate. 

The preparation of enantiomerically pure chemicals is also the theme of the next group of four procedures. The biopolymer polyhydroxybutyric acid, which is now produced on an industrial scale, serves as the starting material for the large scale synthesis of (R)-3-HYDROXYBUTANOIC ACID and (R)-METHYL 3-HYDROXYBUTANOATE. Esters of (-)-camphanic acid are useful derivatives for resolving and determining the enantiomeric purity of primary and secondary alcohols. An optimized preparation of (-)-(1S,4R)-CAMPHANOYL CHLORIDE is provided. The preparation of enantiomerically pure a-hydroxyketones from ethyl lactate is illustrated in the synthesis of (3HS)-[(tert)-BUTYL-DIPHENYLSILYL)OXY]-2-BUTANONE. One use of this chiral a-hydroxyketone is provided in the synthesis of (2S,3S)-3-ACETYL-8-... 

The reaction of ADC compounds with carbenes and their precursors has already been discussed in Section IV,A- In general, the heterocyclic products are not the result of 1,2-addition but of 1,4-addition of the carbene to the —N=N—C=0 system.1 Thus the ADC compound reacts as a 4n unit in a cheletropic reaction leading to the formation of 1,3,4-oxadiazolines. Recent applications include the preparation of spiro-1,3,4-oxadiazolines from cyclic diazoketones and DEAZD as shown in Eq. (14),133 and the synthesis of the acyl derivatives 85 from the pyridinium salts 86.134 The acyl derivatives 85 are readily converted into a-hydroxyketones by a sequence of hydrolysis and reduction reactions. 

Trisubstituted imidazoles have been synthesized from 1,2-diketones or a-hydroxyketones with ammonium acetate in very short reaction times with excellent yields in the presence of l,l,3,3-VAr V ,(V -tetramethylguanidinium trifluoroacetate as an ionic liquid <06SC65>. Iodine acted as an efficient catalyst in the synthesis of 1,2,4,5-tetraarylimidazoles 93 using benzoin 91,... 

OZTs from keto sugars. An original approach for the synthesis of OZTs from carbohydrate-based a-hydroxyketones was recently published by Silva et al.4Sa who investigated the reactivity of carbohydrate-based a-hydroxyketone in the presence of thiocyanic acid. 

Electroreduction of y- and 5-cyano ketones in isoPrOH with a Sn cathode gave a-hydroxyketones with good diastereo-selectivities as cyclization products. The reaction has been used as a key step for the synthesis of, for example, guaiazulene, triquinanes, and dihydrojasmone. Similarly, the corresponding intermolecular couplings were realized [315]. 

According to these heuristic principles, a possible synthesis of prostaglandins that proceeds via an aldol condensation in the last step, would be in principle valid for synthesis of prostanoids of the A and the B series (26a or 26b). but not for those of the E series owing to the great unstability of the resulting aldol (P-hydroxyketone or 1,3-C system) under the reaction conditions [20] (Scheme 4.7). 

In practice, such synthetic scheme has been applied [15] to a formal synthesis of nor-patchoulol (37) which proceeds -via radical intermediates [16]- through the hydroxyketone 36 (Scheme 7.12). 

Alternative precursors for the synthesis of NHCs are thiourea derivatives of type 3. The preparation of such thiones with a symmetrical substitution pattern is achieved by the reaction of a-hydroxyketones like 3-hydroxy-2-butanone with suitable 2-thiones (Fig. 3d) [31] or by reaction of a diamine with thiophosgene [32, 33]. Unsymmetrically substituted thiones 4 possessing a saturated heterocycle have also been described (Fig. 3e) [34, 35]. 

Over the past several years, Mascarenas and co-workers (150-153) utilized the oxidopyrylium ion with variously hetero-substituted olefin tethers. Mascarenas has used this methodology in tandem with a Diels-Alder reaction to prepare tricyclic cycloheptanoid substrates. Further, Mascarenas and co-workers (154—156) achieved the synthesis of optically active oxabicyclic[3.2.1]octane derivatives through the addition of a homochiral p-tolylsulfinyl group substituted at the olefin tether. The Mascarenas group has also used this methodology to prepare the THF portion of ( )-nemorensic acid via oxidative cleavage of the substituted a-hydroxyketone moiety (157) (Scheme 4.78). 

Scheme 6.97). Transformation of this compound to hydroxyketone 260 proceeded as usual in excellent yield. From compound 260, ring A was elaborated resulting in a complete synthesis of testosterone 261 (331). 

Enders and Lotter174) developed an asymmetric synthesis of a-hydroxyketones and vicinal diols using the (S)-proline derivative (S)-l-formyl-2-methoxymethyl-pyrrolidine as chiral auxiliary. However, the a-hydroxyketones and vicinal diols, respectively, were only obtained with low stereoselectivity. 

Terashima et al. 231) reported an asymmetric halolactonization reaction. This highly stereoselective reaction permits the synthesis of intermediates for the preparation of chiral a,a-disubstituted a-hydroxycarboxylic acids (227)231c), a-hydroxyketones (228) 231c), functionalized epoxides (229) 231d,e) and natural products 231h,j). Only amino acids have so far been used as a source of the chiral information in the asymmetric halolactonization reaction. Again, the best results have been obtained by using cyclic imino acid enantiomers, namely proline. 

Direct Nucleophilic Acylation by the Low Temperature, in situ Generation of Acyllithium Reagents a-Hydroxyketones from Ketones Synthesis of 3-Hydroxy-2,2, 3-trimethyloctan-4-one from Pinacolone R. Hui and D. Seyferth, Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139... 

So when the hydroxyketone 49 was needed for a pheromone synthesis, it was made by nucleophilic displacement on the lactone 50 by an organo-lithium compound. This lactone is of the right kind (cf. 45) to be made by a Baeyer-Villiger rearrangement from the cyclohexanone 51 and this can be made by total reduction of the phenol 52 (chapter 36). 

---