2-Cyclohexenones aldehydes

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). 

An unusual reaction was been observed in the reaction of old yellow enzyme with a,(3-unsat-urated ketones. A dismutation took place under aerobic or anaerobic conditions, with the formation from cyclohex-l-keto-2-ene of the corresponding phenol and cyclohexanone, and an analogous reaction from representative cyclodec-3-keto-4-enes—putatively by hydride-ion transfer (Vaz et al. 1995). Reduction of the double bond in a,p-unsaturated ketones has been observed, and the enone reductases from Saccharomyces cerevisiae have been purified and characterized. They are able to carry out reduction of the C=C bonds in aliphatic aldehydes and ketones, and ring double bonds in cyclohexenones (Wanner and Tressel 1998). Reductions of steroid l,4-diene-3-ones can be mediated by the related old yellow enzyme and pentaerythritol tetranitrate reductase, for example, androsta-A -3,17-dione to androsta-A -3,17-dione (Vaz etal. 1995) and prednisone to pregna-A -17a, 20-diol-3,ll,20-trione (Barna et al. 2001) respectively. 

Asymmetric Allylation. One of the recent new developments on this subject is the asymmetric allylation reaction. It was found that native and trimethylated cyclodextrins (CDs) promote enantiose-lective allylation of 2-cyclohexenone and aldehydes using Zn dust and alkyl halides in 5 1 H2O-THF. Moderately optically active products with ee up to 50% were obtained.188 The results can be rationalized in terms of the formation of inclusion complexes between the substrates and the CDs and of their interaction with the surface of the metal. 

Epoxides are reactive substrates, which can easily be isomerized to give aldehydes or ketones. Kulawiec and coworkers have combined a Pd-catalyzed isomerization of mono and diepoxide 6/1-348 or 6/1-349 and 6/1-352 or 6/1-353, followed by an aldol condensation to give either cyclopentenones or cyclohexenones 6/1-350, 6/1-351, 6/1-354 and 6/1-355, respectively (Scheme 6/1.89) [165]. 

Chiral fe-thiourea-type catalysts effectively provide the Baylis Hillman reaction with cyclohexenone and aldehydes.181 In several reactions, thiourea derivatives have been used as significant and specific catalyst because of their intermolecular hydrogen bonding ability (Scheme 74).182 186... 

Ring enlargement.1 A new route to seven-membered ring systems from a cyclohexenone (1) involves a photocycloaddition of ethylene to provide the bicy-clooctanone 2. Addition of lithio-1,3-dithiane to 2 provides the adduct 3, which on reaction with HgO and HBF4 forms an unstable rearranged hydroxy aldehyde... 

The effect of cryptands on the reduction of ketones and aldehydes by metal hydrides has also been studied by Loupy et al. (1976). Their results showed that, whereas cryptating the lithium cation in LiAlH4 completely inhibited the reduction of isobutyraldehyde, it merely reduced the rate of reduction of aromatic aldehydes and ketones. The authors rationalized the difference between the results obtained with aliphatic and aromatic compounds in terms of frontier orbital theory, which gave the following reactivity sequence Li+-co-ordinated aliphatic C=0 x Li+-co-ordinated aromatic C=0 > non-co-ordinated aromatic C=0 > non-co-ordinated aliphatic C=0. By increasing the reaction time, Loupy and Seyden-Penne (1978) showed that cyclohexenone [197] was reduced by LiAlH4 and LiBH4, even in the presence of [2.1.1]-cryptand, albeit much more slowly. In diethyl ether in the absence of... 

Other methods have been described that produce a-iodoenones in specialized cases. Treatment of 3-benzylamino-5,5-dimethyl-2-cyclohexenone with iodine is reported to produce the 2-iodo derivative (Jirkovsky, I. Can. J. Chem. 1974, 52, 55-65). A Wittig-based approach entails the reaction of iodoketophosphoranes with aldehydes (Gorgues, A. Le Coq, A. Bull. Soc. Chim. Fr. 1976, 125-130). 

Tandem 1,4-addition to cycloalkenones constitutes an extremely versatile and elegant methodology for the synthesis of 2,3-disubstituted cycloalkanones, as is evident from its application in areas such as prostaglandin synthesis. Noyori et al. have reported the use of organozinc reagents in copper-catalyzed tandem additions [64]. The zinc enolate resulting from the catalytic enantioselective 1,4-addition of Et2Zn to cyclohexenone reacts readily with an aldehyde in a subsequent aldol condensation. 

The first asymmetric procedure consists of the addition of R2Zn to a mixture of aldehyde and enone in the presence of the chiral copper catalyst (Scheme 7.14) [38, 52]. For instance, the tandem addition of Me2Zn and propanal to 2-cyclohexenone in the presence of 1.2 mol% chiral catalyst (S, R, R)-1S gave, after oxidation of the alcohol 51, the diketone 52 in 81% yield and with an ee of 97%. The formation of erythro and threo isomers is due to poor stereocontrol in the aldol step. A variety of trans-2,3-disubstituted cyclohexanones are obtained in this regioselective and enantioselective three-component organozinc reagent coupling. 

The catalyst is also effective for the reduction of styrenes, ketones, and aldehydes. Cyclohexenone 16 was reduced to cyclohexanone 11 by transfer hydrogenation, and using a higher catalyst loading, styrene 17 was reduced to ethylbenzene 18. The elaboration of [Ir(cod)Cl]2 into the triazole-derived iridium carbene complex 19 provided a catalyst, which was used to reduce aUcene 20 by transfer hydrogenation [25]. 

A simple, commercially available chiral alcohol, a,a,a a -tetraaryl-l,3-dioxo-lane-4,5-dimethanol (TADDOL, 7a), catalyzes the hetero- and carbo-Diels-Alder reactions of aminosiloxydienes with aldehydes and a-substituted acroleins to afford the dihydropyrones and cyclohexenones, respectively, in good yields and high enan-tioselectivities. More recently, it was reported that axially chiral biaryl diols 7b and 7c were more highly effective catalysts for enantioselective hetero-Diels-Alder reactions (Scheme 12.5). ... 

The highly enantioselective Morita-Baylis-Hillman reaction of cyclohexenone with aldehydes is catalyzed by a chiral BlNOL-derived Brpnsted acid 8 in the presence of triethylphosphine as the nucleophilic promoter (Scheme 12.6). ... 

Intramolecular nitrile oxide-alkene cycloadditions also provide efficient access to six-membered rings such as cyclohexanes or decalins that are heavily adorned with functional groups and side chains. For example, this strategy was used to prepare racemic hemaldulcin (213), which is a 3,6-disubstituted cyclohexenone found in a Mexican plant that possesses a strong sweet taste. Starting from (2Z,6E)-famesal (209) (328) (Scheme 6.88), the aldehyde was treated with hydroxylamine... 

A similar reaction with aldehydes results in y-hydroxy-a,/i-unsalurated acids (66% yield, 1 example). The anion 2 undergoes exclusive 1,4-addition to cyclopentenone and cyclohexenone (yields of products, 67% and 85%, respectively). The anion thus is the equivalent of a -carboxyl vinyl anion. 

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