Cyclohexanone allylation

Enamines derived from ketones are allylated[79]. The intramolecular asymmetric allylation (chirality transfer) of cyclohexanone via its 5-proline ally ester enamine 120 proceeds to give o-allylcyclohexanone (121) with 98% ee[80,8l]. Low ee was observed in intermolecular allylation. Similarly, the asymmetric allylation of imines and hydrazones of aldehydes and ketones has been carried out[82]. 

Diacetates of 1,4-butenediol derivatives are useful for double allylation to give cyclic compounds. l,4-Diacetoxy-2-butene (126) reacts with the cyclohexanone enamine 125 to give bicyclo[4.3.1]decenone (127) and vinylbicy-clo[3.2.1]octanone (128)[85,86]. The reaction of the 3-ketoglutarate 130 with cij-cyclopentene-3,5-diacetate (129) affords the furan derivative 131 [87]. The C- and 0-allylations of ambident lithium [(phenylsulfonyl)methylene]nitronate (132) with 129 give isoxazoline-2-oxide 133, which is converted into c -3-hydroxy-4-cyanocyclopentene (134)[S8]. Similarly, chiral m-3-amino-4-hyd-roxycyclopentene was prepared by the cyclization of yV-tosylcarbamate[89]. 

With enamines of cyclic ketones direct C alkylation occurs with allyl and propargyl as well as alkyl halides. The reaction is again sensitive to the polarity of the solvent (29). The pyrrolidine enamine of cyclohexanone on reaction with ethyl iodide in dioxane gave 25% of 2-ethylcyclohexanone on hydrolysis, while in chloroform the yield was increased to 32%. 

Benzene, propyl acetate, allyl acetate, 1-pentanol, cyclohexanone, cyclohexanol, dicyclohexyl ether, cyclohexyl valerate, butyric acid, valeric acid, caproic acid, 1,5-pentanediol, dicyclohexyl succinate, and dicyclohexyl glutarate 30 m DB-FFAP column, 60-200° at 67min. 

Using the 3 mm. by 2 m. gas chromatography column described above, a mixture of stereoisomers of 2-allyl-5-methylcyclohexanone [Cyclohexanone, 5-methyl-2-(2-propenyl)-], prepared by allylation of the enamine of 3-methylcyclohexanone,7a showed peaks at retention times of 8.4 minutes (more stable isomer) and 9.6 minutes. A mixture of the two isomeric 2-allyl-3-methylcyclohexanones and the two isomeric 2-allyl-5-methylcyclohexanones clearly exhibited four distinct peaks on gas chromatography. 

The checkers obtained an additional 2-5 g. of 2-allyl-3-methyl-cyclohexanone by redistilling the column wash and the pot residue through a short-path distillation column. This raised the total yield to 14.9-18.1 g. (54-66%). 

The direct conversion of 3-methylcyclohex-2-enone into 2-allyl-3-methylcyclohexanone provides an interesting example of the utility of the reduction-alkylation procedure. Synthesis of this compound from 3-methy I cyclohexanone would be difficult because the latter is converted mainly into 2-alkyl-5-methylcyelohexanones either by direct base-catalyzed alkylation11 or by indirect methods such as alkylation of its enamine (see Note 13) or alkylation of the magnesium salt derived from its cyclohexylimine.12... 

It is interesting that fmws-2-allyl-3-methy]cyclohexanone is by far the major product of this reduction-alkylation sequence, being formed in greater than the equilibrium ratio (see Note 13). The lithium cnolate would be expected to exist in the two conformations shown below ... 

CYCLOHEXANONE, 2-ALLYL-3-METHYL-(CYCLOHEXANONE, 3-METHYL-2-(2-PROPENYL)-], 52 Cyclohexanone, 2-allyl-5-methyl- Cyclohexanone, 5-methyl- 2-(2-propenyl)-], 55... 

Cyclohexanones, 2-alkyl-5 methyl-, 56 Cyclohexene, 34 Cyclohexene, 1,6-dibromo-, 34 CYCLOHEXENE, 3-METHYL-, 101 Cyclohexene, 1-phenyl- [Benzene, (1-eyclohexen-l-yl)-], 106 2-Cyclohexen-l-ol, 2-bromo-, 34 2-Cyclohexen-l-ol, 3-methyl-, 101 2-Cyclohexen-l-one, 2-allyl-3-methyl-[2-Cyclohexen-l-one, 3-methyl-2-(2-piopenyl)-], 55... 

Cyclohexanone, 2-allyl-, 42,14 Cyclohexanone, condensation with morpholine, 41, 65... 

Sila-Pummerer reaction of the /1-ketosulfoxide 1257 with the enol silyl ether of acetophenone 653 in the presence of BSA 22 a and stannous triflate affords the C-substituted sulfide 1258 in 82% yield and HMDSO 7 [52]. The allylic sulfoxide 1259 reacts with 653 in the presence of TMSOTf 20/DIPEA to give the unsaturated sulfide 1260 in 62% yield or, with the enol silyl ether of cyclohexanone 107a , the unsaturated sulfide 1261 in 63% yield and HMDSO 7 [53] (Scheme 8.21). 

Knowledge regarding biosyntheses has induced several biomimetic approaches towards steroids, the first examples being described by van Tamelen [10] and Corey [11]. A more efficient process was developed by Johnson [12] who, to synthesize progesterone 0-10 used an acid-catalyzed polycyclization of the tertiary allylic alcohol 0-7 in the presence of ethylene carbonate, which led to 0-9 via 0-8 (Scheme 0.3). The cyclopentene moiety in 0-9 is then transformed into the cyclohexanone moiety in progesterone (0-10). 

Ono and coworkers have extended the radical elimination of v/c-dinitro compounds to P-nitro sulfones151 and P-nitro sulfides.138,152 As P-nitro sulfides are readily prepared by the Michael addition of thiols to nitroalkenes, radical elimination of P-nitrosulfides provides a useful method for olefin synthesis. For example, cyclohexanone is converted into allyl alcohol by the reaction shown in Eq. 7.110. Treatment of cyclohexanone with a mixture of nitromethane, PhSH, 35%-HCHO, TMG (0.1 equiv) in acetonitrile gives ahydroxymethylated-P-nitro sulfide in 68% yield, which is converted into the corresponding allyl alcohol in 86% yield by the reaction with Bu3SnH.138 Nitro-aldol and the Michael addition reactions take place sequentially to give the required P-nitro sulfides in one pot. 

Other predicted reactions, not shown in Fig. 32, include rearrangements of the oxiranes to give a cyclohexanone, and various allyl alcohols. These predicted products are entirely consistent with the type of by-product to be expected under such reaction conditions. 

Platinum-catalyzed allylation of aldehydes with allyltin reagents was first reported in 1995.4S7 457b,483 483a Ar0matiC) aliphatic, a,/3-unsaturated aldehydes and even cyclohexanone undergo allylation with allyltributyltins in the presence of PtClgtPP 113)2 >n THF at room temperature or higher temperature (Equations (123) and (124)). Allylplatinum species are considered to be the active intermediates on the basis of related mechanistic studies on palladium catalysis. 

Selective oxidation of allylic alcohols.1 This zircononcene complex when used in catalytic amount can effect an Oppenauer-type oxidation of alcohols, including allylic ones, in the presence of a hydrogen acceptor, usually benzaldehyde or cyclohexanone. This system oxidizes primary alcohols selectively in the presence of secondary ones. Thus primary allylic alcohols are oxidized to the enals with retention of the configuration of the double bond in 75-95% yield. The method is not useful for oxidation of propargylic alcohols. 

Bis-allylic oxidation of 23 and related cyclohexa-1,4-dienes provides a convenient and general preparation of cyclohexa-2,5-dien-l-ones (Scheme 7). These cross-conjugated die-nones are substrates for a variety of photochemical rearrangement and intramolecular cycloaddition reactions. Amide-directed hydrogenations of dienones 24a and 24b with the homogeneous iridium catalyst afford cyclohexanones 25a and 25b, containing three stereogenic centers on the six-... 

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