Cyclization Cyclohexanediones

Enamines of cyclic ketones react similarly (68,131). Thus the enamine (28) gave a goodyield of the monophenylhydrazone of 1,2-cyclohexanedione (193) on reaction with phenyldiazonium fluoborate and subsequent hydrolysis (6S). The products (193) have been cyclized to the corresponding... 

The application of double Fischer indolization has been demonstrated to provide larger amounts of the indolocarbazole 4 from the treatment of the hisphenylhydra-zone 151 with aqueous sulfuric acid (63JCS2504). A considerably more efficient protocol has been devised by Robinson, who obtained 4 in 35% yield on treatment of 1,4-cyclohexanedione bisphenylhydrazone (151) in a mixture of acetic acid and sulfuric acid (63JCS3097). In spite of many recent developments, this is still the method of choice for the preparation of the parent system 4 as the starting materials are cheap and readily available. Cyclization of 151 in ethanol-water containing... 

The utility of base catalyzed condensations of esters to give jS-ketoesters is well known. A straightforward example of this reaction is the intermolecular cyclization of diethyl succinate giving 2,5-dicarbethoxy-l,4-cyclohexanedione, which can in turn be easily decarboxylated to give 1,4-cyclohexanedione. 

Michael additions to acceptor-substituted dienes are often followed by (spontaneous or induced) cyclizations. This was already noted by Vorlander and Groebel4 who obtained a substituted 1,3-cyclohexanedione by treatment of 6-phenyl-3,5-hexadien-2-one with diethyl malonate (equation 5). Obviously, the 1,4-addition product which is formed initially then undergoes cyclization, ester hydrolysis and decarboxylation. Similarly, reaction of methyl sorbate with methyl 4-nitrobutyrate gave the 1,6-adduct which was reductively cyclized to 6-methyl-l-azabicyclo[5.3.0]decane18 (equation 6). 

The mixed hydrazones (667), prepared from diacetyl monobenzoyl hydrazone and arylhydrazines, undergo oxidative cyclization to 2-aryl-jV-benzoyl-4,5-dimethyl-l,2,3-triazol-l-ylimines (668) in 32-76% yield upon treatment with lead tetraacetate in acetonitrile (Scheme 132) <92JOC2252>. The cychzation of bishydrazones to 1,2,3-triazoles can also occur in acidic or basic media. For instance, the tetrahydrobenzo[ /]triazol-4-one (669) is prepared by the base-catalyzed cyclization of the corresponding a-hydrazono oxime (Equation (53)) <85HCA1748>. 3-Methyl-1,2-cyclohexanedione reacts... 

On the basis of these findings, a pathway for this cydoaddition is proposed in Scheme 7.24. The first step is the nucleophilic attack of the carbon atom in the 2-position of 1,3-cyclohexanedione on the Cy atom of the allenylidene complex to give a vinylidene complex, which is transformed into an alkenyl complex by intramolecular nucleophilic attack of the oxygen atom of a hydroxy group of an enol on the C, atom of the vinylidene complex. By the use of Ic with its bulkier alkanethio moiety as a catalyst and at lower temperature, a subsequent intramolecular cyclization may be slow enough to make isolation of the alkylated product possible. 

Dioxo-8a-methyl-l, 2,3,4,6,7,8,8a-octahydronaphthalene has been obtained through the reaction of 2-methyl-l,3-cyclohexane-dione with acetonedicarboxylic acid and formaldehyde,3 4-diethyl-amino-2-butanone methiodide,3 pyridine and 4-diethylamino-2-butanone,4 triethylamine and 4-diethylamino-2-butanone,5 and by cyclization of 2-methyl-2-(3-oxobutyl)-l,3-cyclohexanedione using either aluminum fer/-butoxide or piperidine phosphate as catalyst.6 7... 

Cyclizations involving cyclic 1,3-diones are very effective. Thus 5,5-dimethyl-l,3-cyclohexanedione (dimedone) and 5-phenyl-1,3-cyclohexane-dione react with aldehydes R2CHO to give condensed 4//-pyrans 86a,2,132 86b,63133 86d,63 and 86e.2... 

Enamines generated from 1,3-cyclohexanedione and aminoacetaldehyde acetals can be cyclized in a one-step process by heating the components in benzene in the presence of an acid catalyst (equation 45) (78JOC3541). 

One of the few examples of a synthetically useful 6-exo-trig cyclization from 3-aza-6-heptenyl radicals is found in the total synthesis of ( )-melinonine-E (159, Scheme 31) by Bonjoch et al. [66]. The cyclization precursor, a,P-unsaturated nitrile 157 was prepared from 1,4-cyclohexanedione monoethylene acetal (156) and tryptamine in 5 steps with 41% overall yield. Initially, when 157 was treated with 1.1 equiv. of n-BujSnH and 0.1 equiv. of AIBN in toluene for 16 h, the expected cyclization to the 2-azabicyclo[3.3.1]nonane ring took place to give 158 only as a minor product, along with its C(14) chloro- and dichloro-substituted derivatives as major products. An additional treatment of the crude mixture with 2.2 equiv. of BujSnH brought about the reduction of the C-Cl bonds to provide nitrile 158 in 38% yield over... 

In a reaction similar to that given in equation 25 enaminones derived from 2-amino-D-glucose and cyclohexanediones were cyclized to give 2-substituted indol-4-ones. The corresponding 1-aminofructose derivatives were transformed into 3-substituted in-dolones43 (equations 27 and 28). 

Baylis-Hillman acetates have been conveniently transformed into tri/tetracyclic heterocyclic frameworks containing an azocine moiety via a one-pot multistep protocol involving alkylation, reduction, and cyclization sequence <2007OL2453>. Treatment of Baylis-Hillman acetate 284 with 1,3-cyclohexanedione in the presence of K2CC>3, followed by treatment of the resulting product with Fe/AcOH, gave 77% fused azocine 285 (Scheme 119). 

Compound 466, derived from 1,3-cyclohexanedione 465, cyclizes by treatment with PPA to afford thiophene 467 (Scheme 76) <1996CC177>. 

The addition of ethyl sodiomalonate to olefinic ketones followed by ring closure and /3-keto ester cleavage leads to 1,3-cyclohexanediones. The reaction has been applied to the formation of 2-alkyl-5-phenyl-1,3-cyclohexanediones and is typified by the preparation of 5,5-dimethyl-1,3-cyclohexanedione (85%). Other cyclizations for formation of four-and five-membered rings have been described. ... 

The simplicity and power of this reaction is illustrated by the spontaneous cyclization of the derivative 6, formed from the condensation of (A)-citronellal (7) and 5-n-pentyl-l,3-cyclohexanedione, which occurs with complete stereochemical control (Scheme 7) [223],... 

Benzoyldiaryl ethers are cyclized in good-to-excellent yield by treatment with hot sulphuric acid-acetic acid [3027,3029]. A 2-aminopyran ring is formed when a heterocyclic ketone is heated with a cinnamonitrile and piperidine [3095]. Reduced chromen-5-one are also formed in a basic medium when acroleins are heated with 1,3-cyclohexanediones [2763a]. 

Some systems of different structure have shown their ability to catalyze the formation of a new carbon-carbon bond by reaction of two ketones. The enantioselective aldol reaction between 1,3-cyclohexanedione (173) and different a-bromoketo esters 174 followed by final cyclization gave as the main compound cw-configured 176. Several Cinchona alkaloid derivatives were tested in this transformation, with the dimeric catalyst system 175 in the presence of a proton sponge and an ammonium salt affording the best results (Scheme 4.37) [256], Also dimeric cinchona... 

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