Cyclohexanone aldehyde derivatives from

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]. 

V-Acylation of oxaziridine (54) is of more importance, yielding 2-acyloxaziridines which were unaccessible otherwise until recently. Oxaziridines (54) derived from cyclohexanone, butanone or benzaldehyde are acylated readily by acetic anhydride, acid chlorides or isocyanates. Oxaziridines from aliphatic aldehydes, too unstable to be isolated, may be trapped in situ by benzoylation (67CB2593). 

The reactions of dichlorocarbene with morpholine and piperidine enamines derived from cyclopentanone and cyclohexanone have been reported to lead to ring expanded and a-chloromethylene ketone products (355,356). Similarly a-chloro-a, -unsaturated aldehydes were obtained from aldehyde derived enamines (357). Synthesis of aminocyclopropanes (353,359) could be realized by the addition of diphenyldiazomethane (360) and the methylene iodide-zinc reagent to enamines (367). 

Aldehydes and ketones react reversibly with 2 equivalents of an alcohol in the presence of an acid catalyst to yield acetals, R2C(OR )2, sometimes called ketals if derived from a ketone. Cyclohexanone, for instance, reacts with methanol in the presence of HCl to give the corresponding dimethyl acetal. 

The intramolecular asymmetric Stetter reaction of aliphatic aldehydes is generally more difficult to achieve due to the presence of acidic a-protons. Rovis and co-workers have demonstrated that the NHC derived from pre-catalyst 130 promotes the intramolecular Stetter cyclisation with enoate and alkyhdene malonate Michael acceptors 133. Cyclopentanones are generally accessed in excellent yields and enantioselectivities, however cyclohexanones are obtained in significantly lower yields unless very electron-deficient Michael acceptors are employed... 

Treated with ZnBr2 followed by enamines, phenyl thioethers 829 derived from aryl aldehydes are converted to (l-(phenylthio)alkyl ketones or aldehydes 830 in moderate to good yields (Equation 19). Enamines used in these syntheses are (1) morpholine enamine derived from diethyl ketone, (2) diethylamine enamine of propiophenone, (3) piperidine enamine derived from isovaleraldehyde, and (4) pyrrolidine enamine of cyclohexanone <2000H(53)331>. 

Alkyl- and aryl-hydrazones of aldehydes and ketones readily peroxidise in solution and rearrange to azo hydroperoxides [1], some of which are explosively unstable [2], Dry samples of the p-bromo- and p-fluoro-hydroperoxybenzylazobenzenes, prepared by oxygenation of benzene solutions of the phenylhydrazones, exploded while on filter paper in the dark, initiated by vibration of the table or tapping the paper. Samples were later stored moist with benzene at —60°C to prevent explosion [3], A series of a-phenylazo hydroperoxides derived from the phenyl-or p-bromophcnyl-hydrazones of acetone, acetophenone or cyclohexanone, and useful for epoxidation of alkenes, are all explosive [4], The stability of several substituted phenylazo hydroperoxides was found to be strongly controlled by novel substituent effects [5],... 

Several examples of Bi(OTf)3-catalyzed Mannich-type reactions with various silyl enol ethers are summarized in Table 12. Silyl enol ethers derived from aromatic and aliphatic ketones were reacted with an equimolar mixture of aldehyde and aniline (Scheme 10). The corresponding (3-amino ketones 27 were obtained in good yields (Table 12, entries 1M-) from aromatic-derived silyl enol ethers, except for the more hindered isobutyrophenone derivative. Silyl enol ethers derived from cyclopentanone or cyclohexanone afforded the (3-amino ketones in good yields (Table 12, entries 5 and 6). 

Enamines of aldehydes react with alkyl vinyl ketones.212 Substituted cyclohexanones may be obtained after hydrolysis. Application of this reaction to a,j8-unsaturated aldehydes leads to substituted glutardialdehydes.269 The ratio of the products from the addition of methyl vinyl ketone to the pyrrolidine enamine derived from jS-decalone depends on the configuration of the decalone.76... 

Chiral bis(oxazolines) 51 with an oxalylic acid backbone were used for the Ru-catalyzed enantioselective epoxidation of tran5-stilbene yielding franx-l,2-diphenyloxirane in up to 69% ee [24]. The asymmetric addition of diethylzinc to several aldehydes has been examined with ferrocene-based oxazoline ligand 52 [25], resulting in optical yields from 78-93% ec. The imide 53 derived from Kemp s triacid containing a chiral oxazoline moiety was used for the asymmetric protonation of prochiral enolates [26]. Starting from racemic cyclopentanone- and cyclohexanone derivatives, the enantioenriched isomers were obtained in 77-98 % ee. 

The vinylbenzothiazoles can also function as very efficient Michael acceptors (78TL13). The a-lithio derivative of acetone dimethylhydrazone undergoes clean conjugate addition to the vinylbenzothiazole derived from cyclohexanone to provide, upon quenching the a-lithiobenzothiazole anion with methyl iodide and hydrolyzing the dimethylhydrazone group, the ketone (579) (93% overall, 86 14 cis trans). The pure cis keto benzothiazole was converted to the cis keto aldehyde (580), and then cyclized with p-toluenesulfonic acid to the A -3-octalone (581 Scheme 127). Many other examples of the use of this chemistry for the construction of fused and spiro ring systems have been developed. 

A valuable group of Wittig reagents is derived from a-haloethers. They react with aldehydes or ketones to form vinyl ethers, which on acid hydrolysis are converted into aldehydes containing one more carbon atom. Thus cyclohexanone is converted into cyclohexane carboxaldehyde (2.75). The addition of an aldehyde... 

Enamines are formed when aldehydes or ketones react with secondary amines. The mechanism is given in Chapter 11. The mechanism below shows how they react with alkylating agents to form new carbon-carbon bonds the enamine here is the one derived from cyclohexanone and pyrrolidine. The product is at first not a carbonyl compound it s an iminium ion or an enamine (depending on whether an appropriate proton can be lost). But a mild acidic hydrolysis converts the iminium ion or enamine into the corresponding alkylated carbonyl compound. 

Dihydropyran derivatives can be synthesized facilely by a smooth oxidative Mukaiyama-Michael addition followed by a cyclization with silyl enol ethers in the presence of Dess Martin periodinane (DMP) and pyridine under mild reaction conditions from MBH adducts in a one-pot process (Scheme 4.95). Notably, these dihydropyrans were obtained exclusively as cw-isomers in good yields. Moreover, all the reactions worked very well, irrespective of whether MBH adducts were derived from aliphatic or aromatic aldehydes, and silyl enol ethers were derived from acetophenone, cyclohexanone or cyclopentanone. 

Also, the use of prolinamide derivatives bearing a stereogenic axis such as in the spiro compound 57 (Fig. 4.4) has been further explored in the reaction of acetone (26.5 equiv.) with several aliphatic and aromatic aldehydes at -25°C. Although its high activity permitted to reduce the amount of catalyst to only 1 mol%, the results were in general modest (50-87% yield, 19-76% ee) [116]. More complicated chiral calix[4]-arene based prolinamide 58 (10 mol%) required the use of acetic acid (20 mol%) as co-catalyst to give the aldol products derived from cyclohexanone (7.3 equiv.) and several aromatic aldehydes, with moderated yields and selectivities (35-93% yield, 66-88% de, 50-79% ee) [117],... 

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