4-Hydroxy-5-phenyl-2-pentanone

Favorskii reported the conversion of 3-hydroxy-4-heptanone to 4-hy-droxy-3-heptanone, as well as analogous transformations of 2-hydroxy-3-pentanone and 2-hydroxy-4,4-dimethyl-3-pentanone. These reactions were carried out at elevated temperatures, in ethanol solutions containing a small proportion of sulfuric acid. At the same time, Favorskii reported the isomerization of 2-hydroxypropiophenone to l-hydroxy-l-phenyl-2-pro-panone under the conditions of yeast fermentation—a claim which the evidence given hardly justified and which von Auwers and Mauss disputed. However, Temnikova reported that this conversion does take place in both acid and alkaline media, and the list of what appear to be... 

Thus, a short-range strategy for the synthesis of 4-hydroxy-l-phenyl-pentanone-2 (I) will lead to the two carbonyl compounds methyl benzyl ketone and acetaldehyde as synthesis precursors (Figure 1). Having reached this conclusion it is absolutely necessary to consider whether those two precursors will react by the anticipated aldol condensation to the target compound (I). A closer inspection based on insight into chemical reactivity has to decide that this reaction will not proceed unequivocally to the desired product (I). Rather, a mixture of compounds will be obtained including the... 

The aldol reaction of 2,2-dimethyl-3-pentanone, which is mediated by chiral lithium amide bases, is another route for the formation of nonracemic aldols. Indeed, (lS,2S)-l-hydroxy-2,4,4-trimethyl-l-phenyl-3-pentanone (21) is obtained in 68% ee, if the chiral lithiated amide (/ )-A-isopropyl-n-lithio-2-methoxy-l-phenylethanamine is used in order to chelate the (Z)-lithium cnolate, and which thus promotes the addition to benzaldehyde in an enantioselective manner. No anti-adduct is formed25. 

Metalation ofa-sulfinyl dimethylhydrazones with terf-butylmagnesium bromide, butyllithium or lithium diisopropylamide, and reaction of the generated azaenolates with aldehydes, provides aldol adducts (e.g., 6) as mixtures of diastereomers. Reductive desulfurization leads to fi-hydroxy dimethylhydrazones (e.g., 7) which are cleaved to the desired /(-hydroxy ketones in 25% overall yield10 u. The enantiomeric excesses are about 50%, except for (- )-3-hydroxy-4-methyl-1-phenyl-1-pentanone (8) which was obtained in 88% ee. 

The procedure reported here provides a convenient method for the a-hydroxylation of ketones which form enolates under the reaction conditions. The reaction has been applied successfully to a series of para-substituted acetophenones, 1-phenyl-1-propanone, 3-pentanone, cyclopentanone, cyclohexanone, cycloheptanone, cyclododecanone, 2-methyl cyclohexanone, 2-norbornanone and benzalacetone. In the case of a steroidal example it was shown that a carbon-carbon double bond and a secondary hydroxyl group are not oxidized. A primary amino function, as in the case of p-aminoacetophenone, is not affected.5 Similarly, a tertiary amino ketone such as tropinone undergoes the a-hydroxy at ion reaction.5... 

In exploring various synthetic methods for the preparation of 1,2-oxaphospholene 2-oxides we investigated the reaction of diacetone alcohol (4-hydroxy-4-methyl-2-pentanone) with methyl and phenylphosphonous dichloride, which was reported (1) to proceed as shown in eq (1) to give 2,3,3,5-tetramethyl-l,2-oxaphos-phol-4-ene 2-oxide or the corresponding 2-phenyl derivative. 

Another example presented by this group involved the reduction of ( )-3-hydroxy-5-phenyl-2-pentanone with Sml2 in the presence of ethyl crotonate to afford jjn-y-lactone in excellent yield and diastereoselectivity at three contiguous stereocenters (Scheme 6) [19, 20], Cram cyclic model K was used to explain the selectivity in the formation of the first new stereogenic center. Subsequent coordination of the ethyl crotonate ester group to the Sm" was responsible for the facial selectivity during the formation of the second center [20]. 

Scheme 9.47. A schematic representation of the formation of the enolate anion of 2,2-dimethyl-3-pentanone and its reaction at low temperatures with benzenecarboxaldehyde (benzaldehyde) to form eryt/tro-5-hydroxy-2,2,4-trimethyl-5-phenyl-3-pentanone. Under equilibrating conditions (at 25°C), the corresponding threo-ketone, which has the bulky groups farthest apart and thus is most stable, forms.

Methyl-4-pentanone in ether added dropwise at -78° under argon to an ethereal soln, of di-n-butylborinyl triflate and diisopropylethylamine with stirring, which is continued 0.5 hr., 3-phenylpropanal in ether added at the above temp., allowed to stand 1 hr., added at room temp, to phosphate buffer of pH 7, extracted with ether, which is then evaporated, finally treated 2 hrs. with 30%-H2O2 in methanol 6-hydroxy-2-methyl-8-phenyl-4-octanone. Y 82%. F. e. s. T. Mu-kaiyama and T. Inoue, Chem. Lett. 1976, 559 with 9-borabicyclo[3.3.1]nonyl triflate cf. ibid. 1977, 153. 

Startg. -keto ester in dimethyl sulfoxide added at 25 under argon during 5 min. to a stirred mixture of benzaldehyde and zinc in dimethyl sulfoxide, and stirring continued 11 hrs. 5-hydroxy-4-methyl-5-phenyl-3-pentanone. Y 92%. F. e. s. T. Mukaiyama et al., Chem. Lett. 1976, 95. 

Acetyl-3,5,6-trimethoxyphenyl)-1 -propanone, 2135 3-Butyl-2,4,6-trihydroxy-5-(l-oxopropyl)benzaldehyde, 2135 1,1 -(2-Hydroxy-4,6-dimethoxy-1,3-phenylene)bis-1 -propanone, 2114 1,1 -(6-Hydroxy-2,4-dimethoxy-1,3-phenylene)bis-1 -propanone, 2114 1 - [4-Hydroxy-3 -[2-( 1 -oxopropoxy)ethoxy ]phenyl] -1 -propanone, 1908 1 -[2,4,6-Trihydroxy-3-(1 -oxopropyl)phenyl]-1 -pentanone, 2136 l,r-(2,4,6-Trihydroxy-l,3-phenylene)bis[2-methyl-l-propanone, 2147... 

A soln. of 4-hydroxy-4-methyl-5-phenyl-2-pentanone in 48%-HBr-glacial acetic acid heated 2 hrs. on a steam bath 1,3-dimethylnaphthalene. Y 87-90%. -The above mixture of HBr and acetic acid (Bradsher s reagent) gave higher yields than other acids. F. e. s. P. Ganonne, P. Holm, and L. G. Leitch, Gan. J. Ghem. 45, 2151 (1967). 

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