Hexanal, reductive amidation

Catalytic reductive amidation of hexanal with acetamide gives A-hexylacetamide, using (cyclooctadiene)rhodium(I) chloride dimer as catalyst, together with xantphos ligand and an acid co-catalyst. NMR shows that acetamide adds nucleophilically to... 

The reagent is prepared by reaction or toluene with hexane, ng agent comparable to other lithium VC 1,2-rcduction of enoncs. Reduction proceeds at —78°. However, ketones cr. Esters arc reduced to a mixture of in alcohol can be effected by reduction sodium borohydride. Tertiary amides Ics in generally high yield. Selective ondary halides is possible. 

DIBAH forms ate complexes by action of n-BuLi in hexane [KAl]. In THF-hexane, these ate complexes selectively reduce esters to alcohols, tertiary amides to aldehydes (at 0°C), and a-enones to allyl alcohols (at -78°C). Primary and secondary amides as well as nitriles are unaffected at low temperatures. Primary halides are only reduced at room temperature so these reagents perform selective reductions according to the reaction conditions (Sections 2.1,3.2.5,3.2.9). The uses of DIB AH-Z-Buj A1 ate complexes have also been described [PP2]. 

Now let s draw the forward scheme. The 3° alcohol is converted to 2-methylpropene using strong acid. Anti-Markovnikov addition of HBr (with peroxides) produces l-bromo-2-methylpropane. Subsequent reaction with sodium acetylide (produced from the 1° alcohol by dehydration, bromination and double elimation/deprotonation as shown) produces 4-methyl-1-pentyne. Deprotonation with sodium amide followed by reaction with 1-bromopentane (made from the 2° alcohol by tosylation, elimination and anfi -Markovnikov addition) yields 2-methyl-4-decyne. Reduction using sodium in liquid ammonia produces the E alkene. Ozonolysis followed by treatment with dimethylsulfide produces an equimolar ratio of the two products, 3-methylbutanal and hexanal. 

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