Hydrogenolysis alkyl iodides

Vinyl isonitriles 693 can be deprotonated with LDA in THF at —78 °C to give the vinyl-lithium 694, which has been used as a 3-hydroxypropanoyl anion equivalent. Intermediate 694 reacted with primary alkyl iodides and bromides to form alkylated products 695 and, after hydrolysis, the corresponding ketones, which can be submitted to hydrogenolysis, leading to -hydroxyethyl ketones in good yields (66-90%)"8 (Scheme 180). 

Catalytic hydrogenolysis of alkyl halides is one of the classical methods of alkane syntheses. Among other catalysts, Raney Ni has proved to be quite effective for the hydrogenolysis of iodides (equation 39) . A relatively recent discovery is the reductive dehalogenation of alkyl halides under the conditions of ionic hydrogenation. 

Mel, CH3CN morpholine or diethylamine, methanol, 76-95% yield. These conditions also cleave tlie 4 -pyridyl derivative. The Pet ester is stable to the acidic conditions required to remove the BOC and r-butyl ester groups, to the basic conditions required to remove the Fmoc and Fm groups, and to hydrogenolysis. It is not recommended for use in peptides that contain methionine or histidine since these are susceptible to alkylation with methyl iodide. 

From intermediate 28, the construction of aldehyde 8 only requires a few straightforward steps. Thus, alkylation of the newly introduced C-3 secondary hydroxyl with methyl iodide, followed by hydrogenolysis of the C-5 benzyl ether, furnishes primary alcohol ( )-29. With a free primary hydroxyl group, compound ( )-29 provides a convenient opportunity for optical resolution at this stage. Indeed, separation of the equimolar mixture of diastereo-meric urethanes (carbamates) resulting from the action of (S)-(-)-a-methylbenzylisocyanate on ( )-29, followed by lithium aluminum hydride reduction of the separated urethanes, provides both enantiomers of 29 in optically active form. Oxidation of the levorotatory alcohol (-)-29 with PCC furnishes enantiomerically pure aldehyde 8 (88 % yield). 

The 4-hydroxyl of 8,9-0-isopropylidene derivative 4b has been protected as its 4-t-butyl-dimethyl-silyl ether 4e. Then, the 7-hydroxyl has been converted to its xantate ester 4f, by deprotonation with butyl litium, treatment with carbon disulfide and alkylation with methyl iodide. Deoxygenatiobn of the 7-position has been accomplished by heating with tributyl-tin hydride in xylenes. Then, the cleavage of acetonide and of silyl ether, by heating in 80% acetic acid, followed by hydrogenolysis to remove the benzyl ester, afford 7-deoxy-Neu%Ac-ctMe Im. 

The hydrogenolysis of aryl halides proceeds more readily than the cleavage of alkyl-halogen bonds. Aryl chlorides are rather stable to hydrogenolysis in neutral medium and bromides are dehalogenated only to a moderate extent 24,132 but iodides are readily lost. Aryl fluorides, however, are hydrogenolyzed only under... 

Hydrogen fluoride, catalyst for alkylations, 32, 91 Hydrogen iodide, 31,32 Hydrogenolysis of 2-thio-6-methyl-uracil, 36, 81... 

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