1- Ethyl-2-methyl-3-cyclohexenone

FIGURE 19.120 Biotransformation of 2-methyl-2-cyclohexenone (379) and 2-ethyl-2-cyclohexenone (385)... 

At higher temperatures the mixture of 10 and methyl vinyl ketone yields the 1,4-carbocyclic compound as described previously. Methyl isopropenyl ketone (5), ethyl acetylacrylate (d), 2-cyclohexenone (21), and 1-acetyl-1-cyclohexene (22) also undergo this type of cyclization reaction with enamines at higher temperatures. This cycloalkylation reaction occurs with enamines made of strongly basic amines such as pyrrolidine, but the less reactive morpholine enamine combines with methyl vinyl ketone to give only a simple alkylated product (7). Chlorovinyl ketones yield pyrans when allowed to react with the enamines of either alicyclic ketones or aldehydes (23). 

To a solution of LDA (40mmol) in THF (200ml) cooled at -45°C, methyl dithioacetate (3.92 ml, 40 mmol) was added dropwise. The yellow colour rapidly disappeared. The mixture was stirred for 5 min. 2-Cyclohexenone (3.92 ml, 40 mmol) was then added dropwise. A yellow colour appeared. The resulting mixture was stirred for 15 min. An aqueous solution of ammonium chloride was added and the mixture partitioned between ether and brine. The organic layer was washed with brine, dried with magnesium sulfate and concentrated. Methyl (cyclohexanone-3-yl)dithioacetate (3) (6.75 g, 33.4 mmol, 83%) was isolated by flash chromatography on silica gel using cyclohexane/ethyl acetate (9 1) as the eluent. 

A further example of the use of 2//-thiopyrans as surrogates for m-substituted dienes involves the use of the protected 3,4-dihydio-3-(3-oxobutyl)A//-thiopyranA-onc, 3-[2-(2-methyl-l,3-dioxolan-2-yl)ethyl]-4-[tris(l-methy-lethyl)silyl)oxy-2//-thiopyran 328 as an equivalent of l-ethenyl-2-methylcyclohexene in Diels-Alder reactions. The thiopyran reacted with various maleimides to yield the endo cycloadducts and with methyl propenoate to give the exo adduct under either thermal or Lewis-acid-catalyzed conditions. In the latter case concomitant release of the protected ketone functions occurs, acid-catalyzed cyclization of which generates a fused cyclohexenone ring (Scheme 67). Desulfurization, preferably before the aldol cyclization, leads to derivatives of 2,3,4,4a,5,6,7,8-octahy-dro-4a-methylnaphthalenes < 1997CJC681 >. 

The synthesis of ETHYL a-(BROMOMETHYL)ACRYLATE and METHYL a-(BROMOMETHYL)ACRYLATE makes these valuable intermediates readily available for the synthesis of a-methylene-y-bu-tyrolactone derivatives and other substances as well. A simple procedure for the preparation of 2-alkyl-2-cyclohexenones by reductive alkylation of o-anisic acids is demonstrated in the preparation of 2-HEPTYL-... 

Carbamoylation. The reagent does not react with benzaldehyde or ethyl benzoate. It reacts with alkyl iodides at 80°. A more useful reaction is that with acid halides, particularly acid bromides, which provides a useful route to a-kcto amides. The reagent does not react with cyclohexenone, but does react with methyl vinyl ketone in THF-HMPT (4 1) at -78° to give an adduct in 78% yield. 

The enol silyl ether (56) undergoes a photoinduced reaction in the presence of chloranil to give cyclohexenone and the adduct (57) and the currently available evidence suggests that the reaction proceeds by electron transfer to the photo-activated chloranil to give (56) A photophysical study has appeared of the chromophore-quencher compounds [Au(CCPh)(L )] (L = 10-[(diphenylphosphi-no)methyl]anthracene) and [Au(CCPh)(L )]BPh4 (L = l-[2-(diphenylphosphin-oxy)ethyl]pyridinium], 1 -[2-(diphenylphosphinoxy)ethyl]-4-methyl pyridinium, 1 -[2-(diphenylphosphinoxy)ethyl]-4-tert-butylpyridinium, and 1 -[2-(diphenylpho-sphinoxy)ethyl]triethylammonium in which the Au(CCPh) chromophore is linked by a flexible tether to the acceptors. 

In a related work, a useful procedure for the synthesis of cyclohexenones was also developed by means of the reaction of ethyl benzoylacetate with methyl alkenyl ketones, using primary amine 129 as catalyst in this case. This reaction also consisted of a Michael/intramolecular aldol reaction sequence starting... 

Yields of primary and secondary alcohols are generally excellent, but esters such as methyl benzoate were not reduced. Results of typical examples are listed in Table I. Both 2 and 3 predominantly afforded 2-cyclohexenol as the 1,2 reduction product from 2-cyclohexenone. Chemoselectivity in the reduction was also demonstrated by the competitive reduction of a mixture of pentanal and cyclohexanone. The ratios of primary and secondary alcohols were 75/25 for 2 at 0 °C and 79/21 for 3 at room temperature. These values are fairly larger than the corresponding one (63/37) from a mixture of butanal and methyl ethyl ketone reduced by LiAlH at 25 but smaller than those from a mixture of hexanal and cyclohexanone with LiAlH(0-f-Bu)3 at 0 °C (87/13) and LiAlH(OCEt3)3 at 0 °C (94/6).10... 

These reactions are broadly classified as normal and inverse electron demand Diels-Alder reactions. In normal electron demand Diels-Alder reactions (NED D-AR), diene system acts as electron-rich HOMO system and dienophile as electron-seeking LUMO system, while in inverse electron demand Diels-Alder reactions (lED D-AR), diene system serves as LUMO and dienophile as HOMO [22]. For example, reaction of cyclopentadiene 31 with methyl acrylate gives 32 in NED D-AR [23] and of ethoxyethylene with P-(2-cyclohexenone)-ethyl acrylate 33 gives 34 in NED D-AR [24]. 

Changing the substituent on the p-position of the cyclohexenone from methyl to ethyl, butenyl or phenyl leads to significant drops in conversion and enantioselectivity. 

A mixture of 3-methyl-2-cyclohexenone, Li-diisopropylamide, hexamethylphos-phoramide, and tetrahydrofuran stirred 1 hr. at -60° under N2, then a soln. of ethyl a-phenylthiocrotonate in anhydrous tetrahydrofuran added at -75°, and stirred 1.5 hrs. at -70 to -50° ethyl l,3-dimethyl-5-oxo-2-(phenylthio)bicyclo-[2.2.2.]octane-2-carboxylate. Y 77%. F. e. s. H. Hagiwara, K. Nakayama, and H. Uda, Bull. Chem. Soc. Japan 48, 3769 (1975). 

Figure 4.3. (a) Methyl ethyl ketone, (b) Methyl vinyl ketone introduction of the double bond in (b) causes an upfield shift of the resonance of the carbonyl carbon, (c) Cyclohexenone the carbon p to the carbonyl group resonates at a lower field because of the electron-withdrawing influence of the carbonyl group. 

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