Stereochemistry cyclohexanones

Attempts have been made to account for the stereochemistry of hydride reductions of asymmetric cyclohexanones. Until recently the most widely accepted view was that of Dauben, Noyce and their co-workers, who... 

Some instances of incomplete debromination of 5,6-dibromo compounds may be due to the presence of 5j5,6a-isomer of wrong stereochemistry for anti-coplanar elimination. The higher temperature afforded by replacing acetone with refluxing cyclohexanone has proved advantageous in some cases. There is evidence that both the zinc and lithium aluminum hydride reductions of vicinal dihalides also proceed faster with diaxial isomers (ref. 266, cf. ref. 215, p. 136, ref. 265). The chromous reduction of vicinal dihalides appears to involve free radical intermediates produced by one electron transfer, and is not stereospecific but favors tra 5-elimination in the case of vic-di-bromides. Chromous ion complexed with ethylene diamine is more reactive than the uncomplexed ion in reduction of -substituted halides and epoxides to olefins. ... 

Wittig-type olefination has been reported. The reaction is thought to involve the salt (47) and shows little stereoselectivity. 2.2.2 Ketones.- The stereochemistry of olefination of 2,3-epoxy- and protected 2-hydroxy cyclohexanones with ethylidenetriphenyl-... 

The first approach to oxa-[3 + 3] annulation precursor 8 would rely on late-stage oxidation of the cyclohexanone motif in 10 to the diketone, and 10 can be accessed through a sequence of 1,4-conjugate addition of a Me-nucleophile followed by trapping with a homoallyl electrophile 9 to set the A-ring stereochemistry (Scheme 8.1). Unfortunately, while the addition of Me2CuLi proceeded smoothly, no alkylation using iodide 9 was observed instead, only a mixture of 2,3-dimethylcyclohexanones and recovered iodide were isolated. 

A large number of studies have addressed the condensation of cyclic ketones with both aliphatic and aromatic aldehydes under conditions that reflect both thermodynamic (cf. Table 2) and kinetic control of stereochemistry. The data for cyclohexanone enolates are summarized in Table 8. Except for the boryl enolates cited (6), the outcome of the kinetic aldol process for these enolates... 

The enolates derived from cyclic ketones are necessarily. E-isomers. The enolate of cyclohexanone reacts with benzaldehyde to give both possible stereoisomeric products under kinetically controlled conditions. The stereochemistry can be raised to about 6 1 in favor of the anti isomer under optimum conditions.7 8... 

Indicate the stereochemistry of the major alcohol that would be formed by sodium borohydride reduction of each of the cyclohexanone derivatives shown ... 

Chiral sulfinimines 236 are very useful intermediates for the preparation of enantiomer-ically pure primary amines 237 (equation 158) . This reaction has been applied to the synthesis of a-amino acids . For sulfinimines obtained from simple ketones, lithium reagents are preferable for the addition , while for cyclic ketones organomagnesium compounds gave the best results. Addition of alkyl and aryl Grignard compounds to sulfinimines, derived from 3- and 4-substituted cyclohexanones, proceeds with excellent diastereoselectivity, depending on the stereochemistry of the ring substituents rather than the sulfinyl group . 

It has however been suggested by Cieplak (9) that the stereochemistry of nucleophilic addition to cyclohexanone is determined by a combination of steric and stereoelectronic effects. According to this interesting model, steric hindrance favors the equatorial approach while electron donation favors the axial approach. The stereoelectronic effect favors the axial approach because the axial C —H bonds next to the carbonyl group (C — Ha and Cn-Ha) are better electron donors than the Cn-C-j and Cc-Cfi a bonds (cf 7A 7 and 7A-8). J... 

The same authors studied the stereochemistry of alkylation of 4-t-butyl-cyclohexanone. Alkylation of enolate ion 467 with triethyloxonium fluorobor-ate yielded a mixture of 0-alkyl product and approximately equal amounts of... 

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