Ketone-phosphine oxide, reduction

Under radical conditions tributyltin hydride reduced a-chlorocarbonyl compounds to the corresponding saturated carbonyl derivatives but in the presence of phosphine oxides (HMPA or BU3PO) chemose-lective reduction of the carbonyl group was observed. a-Chloro ketones and aldehydes were reduced with this reagent combination to give good yields of the chlorohydrins. The choice of ligand was important as neither phosphines nor amines were effective substitutes for the phosphine oxides. 

Although Smh is more chemoselective than traditional dissolving metal reagents, it does react with sulfoxides, epoxides, the conjugated double bonds of unsaturated ketones, aldehydes and esters, alkyl bromides, iodides and p-toluenesulfonates. It does not, however, reduce carboxylic acids, esters, phosphine oxides or alkyl chlorides. In common with most dissolving metal systems, ketones with an a-hetero substituent suffer loss of the substituent rather than reduction of the carbonyl group. ... 

In Homer s original work, phosphine oxides (202) were treated with potassium r-butoxide or sodamide and allowed to react with an aldehyde or ketone to form the alkene (203) directly (Scheme 28). Homer observed that the use of a lithium anion resulted in the isolation of Ae p-hydroxyphosphine oxide (204). In addition, he found that the intermediate hydroxyphosphine oxide could be obtained by LAH reduction of the ketophosphine oxide. Warren and coworkers t ve utilized and expanded upon these techniques by isolating and separating the diastereomeric, frequently crystalline, p-hydroxyphosphine... 

Use of Chiral Phosphine-Oxide in the Catalytic Enantioselective Borane Reduction of Ketones... 

On the synthetic side, single diastereomers of P-keto phosphine oxides have been generated from intermolecular acylation of phosphine oxides using either chiral esters or chiral phosphine oxides. In most cases, reduction of the ketone products was not affected by the presence of extra chiral centres. Addition of metallated phosphine oxides to proline-derived ketoaminals provides a new route to optically active P-hydroxy phosphine oxides. The P-hydroxy phosphine oxide 97 has been prepared by the caesium fluoride mediated reaction of silyl-substituted phosphine oxide 98 and benzaldehyde." The synthesis of two (E)-(6-hydroxy-2-hexen-l-yl)diphenylphosphine oxides (99) has been reported. The Horner-Wittig reactions of these compounds with various carbonyl compounds... 

Warren has used a variation of his phosphine oxide-based olefination method to synthesise single isomers (E or Z) of unsaturated carboxylic acids.23 a-Diphenylphosphinoyl ketones (32) are reduced by sodium borohydride to give diastereomeric mixtures of the corresponding alcohols (33) and (34). These alcohols can be converted to the lactones (35) and (36) which can be separated and individually converted stereospecifically into (Z)-(37) and (E)-(38) alkenes by base treatment (Scheme 6). In many cases it is possible to reduce p-ketophosphine oxides (39) and enones (41) stereoselectively to the ery/Aro-alcohols (40) and (42), respectively, using sodium borohydride in the presence of cerium chloride (Scheme 7).24 An earlier report that reduction in the presence of cerium salts did not cause reversal of stereochemistry compared to reduction with borohydride alone appears to be true only of the compounds studied in that report. The carbanions of 3-hydroxypropylphosphine oxides (43) have been reported to undergo O- to C-acyl transfer to give the p-ketoalkylphosphine oxides... 

Diaryl ketones are directly reduced to hydrocarbons with EtiSiH-BFi OEt2. In the reduction of phosphine oxides" (i-PrO)4Ti is used as the Lewis acid catalyst. 

One of the limitations of the Warren s adaptation of Homer-Wittig olefina-tion, the failure of the (Z)-selective route when the alkene has a branched chain substituent, has now been overcome. Reduction of the p-ketophosphonates carrying a-branches, e.g. (112) and (113), with sodium borohydride and cerium chloride gives excellent a / -stereoselectivity and hence (Z)-alkene on base-induced elimination. Enantioselective synthesis of both jy -(115) and anti- ll) P-hydroxy-phosphine oxides has been achieved with up to 90% e.e. through two separate approaches. The jyn-isomer was obtained by reduction of the corresponding ketone (114), while the anti-isomer is the product of the reaction of the oxazolidine substituted aldehyde (116) with lithiated diphenylmethyl-phosphine oxide (Scheme 10). A new, highly stereoselective approach to trisubstituted alkenes has been reported. Cerium(III) chloride-promoted... 

Subsequent treatment with sodium hydride in DMF gave the (Z)-alkene, a-isosafrole (577). If 573 reacted first with butyllithium and then with the analogous ester (578), the keto-phosphine oxide 579 was produced. Reduction of the ketone with sodium borohydride gave predominantly (>=6 1) the anti isomer 580, which gave the ( )-alkene 581 upon reaction with sodium hydride. An interesting application of this methodology is to extend the chain of an aldehyde by one carbon (R—CHO RCH2CHO). i ... 

Reductive opening of epoxides. The selective opening of a, 3-epoxy ketones leads to (3-hydroxy ketones. A phosphine oxide is used as ligand. 

A clearly innovative catalytic system was reported by Nakajima and co-workers [48], who introduced chiral phosphine oxides as suitable Lewis bases for activating trichlorosilane in stereoselective transformations. Indeed trichlorosilane has been used in the conjugate reduction of a,p-unsaturated ketones in the presence of a catalytic amount of a chiral Lewis base. The reduction of 1,3-diphenylbutenone promoted by catalytic amounts of 2,2 -bis(diphenylphosphanyl)-l,l -binaphthyl dioxide (Cat. 15, BINAPO) at 0°C led to the corresponding saturated compound in 97% yield and a somehow surprising, but very good, 97% ee (Scheme 15.19). 

Example 3.1 Enantioselective reduction of ketones to sec alcohols 11-14 is completed by Rh(I) catalytic complexes with three chbal ligands, one phosphine oxide and two bidentate phosphines (Scheme 3.2) [5-7]. 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

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