Cycloalkenes from coupling

In 1977, McMurry and Kees [152] developed a titanium-induced intramolecular coupling procedure to form cycloalkenes from dicarbonyl compounds. Mechanistically, as shown in Scheme 85, the coupling reaction proceeds by an initial pinacol dimerization of the dicarbonyl 253 to 254, followed by titanium-induced deoxygenation to afford alkene 255. 

An interesting reaction takes place when diketones with the keto groups in positions 1,4 or more remote are refluxed in dimethoxyethane with titanium dichloride prepared by reduction of titanium trichloride with a zinc-copper couple. By deoxygenation and intramolecular coupling, cycloalkenes with up to 22 members in the ring are obtained in yields of 50-95%. For example, 1-methyl-2-phenylcyclopentene was prepared in 70% yield from 1-phenyl-1,5-hexanedione, and 1,2-dimethylcyclohexadecene in 90% yield from 2,17-octa-decanedione [206, 210]. 

The cycloaddition reactions of isoquinolinium species produce fused isoquinoline products. The Af-ylide of 53, formed with base addition, couples with alkenes <99S51> or imines <99T7279> to afford tricyclic products, such as 54. Pyrrole-fused isoquinolines result from the reaction between mUnchnone imine intermediates and a,yff-ethylenic esters <99EJOC297>. N-Arylimides undergo 1,3-dipolar cycloaddition with strained frani-cyclooctenes, as opposed to common cycloalkenes, to tdford the pyrazolidine-fused ring system <99H(50)353>. 

The McMurry coupling is most useful for the intramolecular reduction of aldehydes and ketones to form cycloalkenes with ring size varying from 3 to 36. The medium and large rings are usually formed with the -configuration . 

The reductive coupling of carbonyl compounds with formation of C-C double bonds was developed in the early seventies and is now known as McMurry reaction [38, 39]. The active metal in these reactions is titanium in a low-valent oxidation state. The reactive Ti species is usually generated from Ti(IV) or Ti(III) substrates by reduction with Zn, a Zn-Cu couple, or lithium aluminum hydride. A broad variety of dicarbonyl compounds can be cyclized by means of this reaction, unfunctionalized cycloalkenes can be synthesized from diketones, enolethers from ketone-ester substrates, enamines from ketone-amide substrates [40-42], Cycloalkanones can be synthesized from external keto esters (X = OR ) by subsequent hydrolysis of the primary formed enol ethers (Scheme 9). 

The reaction has been most often applied to the synthesis of cycloalkenes, since the acyclic version shows low stereoselectivity. A modification of the original Tipson- ohen conditions has been developed by Fraser-Reid and coworkers for the elaboration of carbohydrate derivatives, in which sodium iodide in conjunction with Zn or Zn-Cu couple in refluxing DMF is used to effect the elimination. As can be seen from the examples shown in equations (14) and (15), the reaction proceeds with equal ease for both cis and trans isomers. 

In a laser flash-photolysis study, 2-phenyladamantene was generated in benzene at room temperature from 3-noradamantyl(phenyl)diazomethane. This strained cycloalkene decays with second-order kinetics to give a dimer, and reacts much faster with O2 and Bu3SnH than with methanol, thus revealing a substantial radical character. Diphenyldiazomethanes possessing stable /er -butylaminoxyl and Ullman s nitronyl nitroxide radicals, e.g. (25), have been prepared by photolysis of the parent diazomethanes. Analysis of ESR fine structures showed that the carbene and radical centres couple ferromagnetically in these molecules, as expected. 

Photolysis in hydrocarbon solvents leads to rearranged products similar to those from other cycloalkenes, as well as hydrogen abstraction and coupling products. ... 

Heck reactions with arenediazonium trifluoroacetates are more efficient because these salts are more soluble in organic solvents than the tetrafluoroborates. a-Benzylidene-y-butyrolactones are successfully prepared from a-methylene-y-butyrolactone and arenediazonium salts or Arl. " The coupling of cycloalkenes with Arl in water at 225° (no other. solvents) can be catalyzed by Pd(OAc)2-NaOAc alone, but yields are low to moderate. ... 

Cycloalkenes of ring size 4—16 are prepared in good yield by treatment of dicarbonyl compounds (31) with the reagent prepared from TiCls and a zinc/copper couple. The reaction is general for both aldehydes and ketones, and... 

The proton spin-coupling constants in a number of cycloalkenes, including cyclo-hexa-1,3-diene and cyclohexene, have been calculated using a finite-perturbation INDO method and with a geometry taken from electron diffraction studies. For cy-clohexa-1,3-diene the following values (in Hz) were calculated, with experimental values in parentheses 1. 63 (9.64) 3, 1.7 (1.02) 1.8 (1.12) J2 3, 6.3 (5.04) for... 

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