Reductive intermolecular

A reductive intermolecular Heck heteroarylation (hydroheteroarylation) of A-protected azabicyclo[2,2,l]heptene 165 has been used to construct 7-azabicyclo[2.2.1]heptane 166 in moderate yield [131, 132]. An asymmetric version of such a transformation to provide enantiomerically-enriched iV-protected epibatidine has also been described [128, 133]. It was found that introduction of Noyori s BINAP ligand resulted in the best enantioselectivities with 72-81% ee and a 53% yield. By using either the (R)- or (S)-BINAP ligand, either enantiomer was easily accessible. 

Scheme 7.47 Tandem conjugate reduction/intermolecular Mannich reaction.

Epibatidine and ( )-homoepibatidine Reductive intermolecular HR of a hetaryl iodide [477[... 

Far from being limited to cyclisation reactions, Sml2 is also a very powerful reagent for the promotion of reductive intermolecular crosscoupling reactions. The ability to fine-tune the reagent using a range of additives can deliver superb yields and stereoselectivity. 

The acylpalladium complex formed from acyl halides undergoes intramolecular alkene insertion. 2,5-Hexadienoyl chloride (894) is converted into phenol in its attempted Rosenmund reduction[759]. The reaction is explained by the oxidative addition, intramolecular alkene insertion to generate 895, and / -elimination. Chloroformate will be a useful compound for the preparation of a, /3-unsaturated esters if its oxidative addition and alkene insertion are possible. An intramolecular version is known, namely homoallylic chloroformates are converted into a-methylene-7-butyrolactones in moderate yields[760]. As another example, the homoallylic chloroformamide 896 is converted into the q-methylene- -butyrolactams 897 and 898[761]. An intermolecular version of alkene insertion into acyl chlorides is known only with bridgehead acid chlorides. Adamantanecarbonyl chloride (899) reacts with acrylonitrile to give the unsaturated ketone 900[762],... 

Aldehydes can undergo an intermolecular oxidation—reduction (Canni22aro reaction) in the presence of base to produce an alcohol and a carboxyUc acid salt. Any aldehyde is capable of participating in such a reaction, however, it is more common for those containing no protons on the alpha carbon, for example... 

Manufacture. Hydroxypivalyl hydroxypivalate may be produced by the esterification of hydroxypivaUc acid with neopentyl glycol or by the intermolecular oxidation—reduction (Tishchenko reaction) of hydroxypivaldehyde using an aluminum alkoxide catalyst (100,101). 

A number of reductive procedures have found general applicability. a-Azidoketones may be reduced catalytically to the dihydropyrazines (80OPP265) and a direct conversion of a-azidoketones to pyrazines by treatment with triphenylphosphine in benzene (Scheme 55) has been reported to proceed in moderate to good yields (69LA(727)23l). Similarly, a-nitroketones may be reduced to the a-aminoketones which dimerize spontaneously (69USP3453279). The products from this reaction are pyrazines and piperazines and an intermolecular redox reaction between the initially formed dihydropyrazines may explain their formation. Normally, if the reaction is carried out in aqueous acetic acid the pyrazine predominates, but in less polar solvents over-reduction results in extensive piperazine formation. 

A typical situation is when (5i > (5q, so that the tunneling distance Qo is overcome mostly at the expense of intermolecular vibration q. The probability p q) is exponentially small, but it is to be compared with the exponentially small barrier transparency, and reduction of the tunneling distance Qo — qhy promoting vibrations may be very large. 

Carboximide 160, the C35-C42 fragment, can be traced retro-synthetically to phosphonate 169 and aldehyde 170. In the synthetic direction, the C35-C36 bond in 160 could be constructed by an intermolecular Horner-Wadsworth-Emmons (HWE)70 coupling of intermediates 169 and 170. Reduction of the unsaturated coupling product and exchange of silyl protecting groups would then furnish compound 160. 

These fragments either combine intramolecularly to form the ortho and para nitro compounds or dissociate completely and then undergo an intermolecular reaction to form the same products. The theory was not developed to include a detailed transition state and no mention was made of how the para isomer was formed. Reduction of the cation-radical could give the amine (which was observed experimentally76), but one would expect the concurrent formation of nitrogen dioxide and hence nitrite and nitrate ions however, the latter has never been... 

These results may easily be rationalized by assuming that the formation of hydroxy sulphoxides 91, 92 and 93 from hydroperoxysulphides 89 and 90 is an intramolecular oxidation-reduction reaction proceeding through a five-membered transition state 94. However, an alternative intermolecular mechanism in which the approach of the oxidant is directed by the hydroperoxy or the hydroxy function in the reductant cannot be excluded. 

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