Pinacolones synthesis

Synthesis Ketone A is just pinacolone, the product of the pinacol rearrangement (frames 154-5). 

Dienones of this class are useful starting materials for the preparation of bicyclic compounds via Diels-Alder reactions1 4 and for the synthesis of small ring compounds.6 The 2,4-dienone can be converted quantitatively to the 2,5-isomer by treatment with fuming sulfuric acid and subsequent hydrolysis.6 The oxidation procedure is also applicable to the conversion of mesity-lene to mesitol or of isodurene to isodurenol,7 and can be used to convert tetramethyl ethylene quantitatively and directly to pinacolone.8... 

A recent synthesis of the phenylisoserine side-chain of taxol is shown in Scheme 18. The enone 21 was obtained in high yield by condensation of benzal-dehyde with pinacolone. Employing the non-aqueous two-phase epoxidation protocol, epoxide 22 was obtained in 76% yield and 94% e.e. Recrystallisation of the epoxide furnished the desired enantiomer in 97 % e. e. Subsequent manipulations of the epoxy-ketone gave the taxol side-chain 23 with the required stereochemistry (Scheme 18). 

The total synthesis of the antifungal alkaloid K252a has been reported in which the indolocarbazole nucleus is constructed using novel rhodium carbenoid chemistry <1995JA10413, 1997JA9641>. Thus, reaction of 2,2 -biindole with diazolactam 173 in the presence of rhodium acetate in degassed pinacolone produces indolocarbazoles in moderate yields (Equation 107). 

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... 

An interesting approach to the synthesis of indoles is the combination of directed orr/w-lithiation followed by an S l reaction324. Thus, the selective or o-lithiation of 2-fluoropyridine (262) by LDA followed by iodination afforded 2-fluoro-3-iodopyridine (263) in high yield (75%). Substitution of the 2-fluorine atom under S Ar conditions is a convenient synthesis of 2-substituted 3-iodopyridines (264) (equation 169), which can react with acetone or pinacolone enolate ions in liquid ammonia, followed by acidic treatment, to give the corresponding substituted 7-azaindoles (265) [R = H, R = Me (75%), R = t-Bu (78%) R = Me, R = f-Bu (70%), R = Me (95%)] (equation 170). 

The synthesis route for (a) starts with the reaction between bromo pinacolone and triazole, followed by addition of a benzyl chloride derivate and hydrogenation of the carbonyl... 

The enantioselective reduction of unsymmetrical ketones to produce optically active secondary alcohols has been one of the most vibrant topics in organic synthesis.8 Perhaps Tatchell et al. were first (in 1964) to employ lithium aluminum hydride to achieve the asymmetric reduction of ketones9 (Scheme 4.IV). When pinacolone and acetophenone were treated with the chiral lithium alkoxyaluminum hydride reagent 3, generated from 1.2 equivalents of 1,2-0-cyclohexylidene-D-glucofuranose and 1 equivalent of LiAlHzt, the alcohol 4 was obtained in 5 and 14% ee, respectively. Tatchell improved the enantios-electivity in the reduction of acetophenone to 70% ee with an ethanol-modified lithium aluminum hydride-sugar complex.10... 

Both enantiomers of 2-amino-3-(3-hydroxy-5-/< t/-butylisoxazol-4-yl)propanoic acid (ATPA) 69, an analogue of the neuroexcitant 2-amino-3-(3-hydroxy-5-methylisoxazoM-yl)propanoic acid (AMPA), were synthesized in 33% overall yield (from pinacolone) and 99% ee. The enantiomerically pure glycine derivative (A )-66 was coupled with 4-bromomethyl-2-methoxymethyl-5-A r/-butyl-3(2//)-isoxazolone 67 to give the intermediate (26, 5A )-68, which was hydrolyzed under mild conditions to give enantiopure (A )-69. The use of (R)-66 allowed the synthesis of R)-69 (Scheme 17) <2000TA4955>. 

Preparation of Monomers. Methyl vinyl ketone (MVK) was obtained from Pfizer Chemical Division, New York, and distilled to remove the inhibitor. Methyl isopropenyl ketone (MIPK) was prepared by the aldol condensation of methyl ethyl ketone and formaldehyde, according to the method of Landau and Irany 0. The major impurity in this monomer is ethyl vinyl ketone (5. The monomer was redistilled before use. 3 Ethyl 3 buten 2 one (EB) was prepared by the aldol condensation of methyl propyl ketone and formaldehyde. Ethyl vinyl ketone (EVK) was prepared by a Grignard synthesis of the alcohol, followed by oxidation to the ketone. t-Butyl vinyl ketone (tBVK) was prepared from pinacolone and formaldehyde by the method of Cologne (9). Phenyl vinyl ketone (PVK) was prepared fay the dehydrochlorlnatlon of 0 cbloro propiophenone (Eastman Kodak). Phenyl isopropenyl ketone (PPK) was prepared by the Mannich reaction using propiophenone, formaldehyde and dimethylamine HCl. 

All classes of vicinal diols (primary, secondary, tertiary, alkyl- or aryl-substituted) will undergo the pinacol rearrangement, and many acids and solvents have been used for this purpose. Various procedural modifications have been introduced over the years for particular glycols, but sulfuric acid remains the most commonly employed catalyst. The use of 25% H2SO4, as recommended in the procedure of Adams, affords pinacolone in essentially quantitative yield. In some instances better results are obtained when cold concentrated acid is used as the solvent. The choice of reagents and conditions is important, and can completely alter the course of the reaction. For example, pinacol also serves as the starting material for the synthesis of 2,3-dimethylbutadiene, formed by slow distillation of a mixture of the diol and catalytic HBr. ... 

Synthesis of the morpholine enamine from pinacolone (3,3-dimethyl-2-butanone) by the modified TiC -method discussed above was complicated by considerable self-condensation of the ketone. 

The byproduct, 2,2,3,6,6-pentamethyl-3-hepten-5-one, was difficult to separate from the enamine by distillation. When the conditions optimized for enamine synthesis from methyl isobutyl ketone were applied to the synthesis from pinacolone, ca. 30 % of the byproduct was formed. A response surface study was undertaken to overcome the problem and to determine how the experimental conditions should be adjusted to achieve a maximum yield of the enamine, with a concomitant suppression of the formation of the byproduct. 

Fig. 14.2 Variation in the conditions affording the maximum yield in the synthesis of morpholine enamines from a series of carbonyl compounds (1) methyl isopropyl ketone, (2) pinacolone, (3) methyl isobutyl ketone, (4) methyl neopentyl ketone, (5) diethyl ketone, (6) diisopropyl ketone, (7) ethyl isobutyl ketone, (8) diisobutyl ketone, (9) isobutyraldehyde,...

The diastereoselective and enantioselective synthesis of optically active 2-amino-3,3-dimethylbutanes was achieved as follows pinacolone was reacted individually with ( + )-(/ )-and ( —)-(S)-phenylethylamine to afford the corresponding chiral ( )-imines. Reduction of the imines with borane-tetrahydrofuran complex resulted in addition of hydride to the less hindered face of the azomethine to give (R,R)- and (S. -benzylamine, respectively, which, on hydrogenolysis (10% Pd/C), afforded (7 )- and (5 )-2-amino-3,3-dimethyl butane, respectively, with high enantiomeric purity (ee >99.5%)3. 

Indanedione derivatives, i.e. the derivatives of 2-acyl-1,3-indanedione, are also compounds with anticoagulant properties (Kabat et al., 1944 Shapiro et al., I960). Their synthesis starts from phthalic acid dimethylester (29). In the presence of metallic sodium this compound reacts with methyl-/-butyl ketone (pinacolon, 30) to produce 2-pivaloylindane-l,3-dione (pindone, 31). 

Triazolyl-0,N-acetals (53) can be synthesised by several methods (Meiser et al., 1972 Kramer et al., 1973). Synthesis generally starts from pinacolone (57), which is halogenated ... 

The yield of the product carbonyl compounds can be very high if suitable experimental conditions are applied. The catalyst of choice under homogeneous conditions is sulfuric acid, either dilute or concentrated this enables the synthesis of pinacolone in almost quantitative yield [11]. Even when selective rearrangement occurs, however, a complex mixture of rearrangement products might be formed, depending on the structure of the starting compound. For example, diol 3 or any... 

Beilstein Handbook Reference) AI3-03075 BRN 1209331 t-Butyl methyl ketone tert-Butyl methyl ketone EINECS 200-9204 HSDB 5210 Ketone, t-butyl methyl Ketone, tert-butyl methyl Methyl t-butyl ketone Methyl tert-butyl ketone NSC 935 Pinacolin Pinacoline Pinacolone Pinakolin. Used in chemical synthesis, manufacture. Liquid mp = -52.5° bp = 106.1° d = 0.7229 slightly soluble in H2O (2.5 g/100 ml), more soluble in organic solvents LD50 (rat orl) = 610 mg/kg. Lancaster Synthesis Co. Mallinckrodt inc. Sigma-Aldrich Fine Chem. 

Diketones. Saegusa et al. have reported the synthesis of 1,4-diketones by treatment of Uthium enolates of methyl ketones with cupric chloride (1 eq.) in DMF at -78°. Yields of coupled products are high in the case of ketones with only one enohzable hydrogen (pinacolone and acetophenone) ... 

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