Ketones, 2- -1 -alkenyl reaction with amines

Quaternization of the nitrogen atom in a heterocyclic system can activate the ring towards addition reactions. An oxazoline moiety was converted to an aldehyde in 97% overall yield by alkylation of oxazoline with MeOTf, reduction with sodium boro-hydride, and hydrolysis of the resulting aminal (eq 10). Alternatively, treatment of an TV-methylated oxazolium triflate with a Grignard reagent followed by aqueous acid produced a ketone. Reaction of alkenyl oxazoles with MeOTf induced spontaneous intramolecular [4 -i- 2] cycloaddition at room temperature leading to a hydroindole or a hydroisoquinoline after reduction by sodium borohydride (eq 11). ... 

The migration of a C=C bond to form a C=N bond was also observed with hydro-xylamine [78, 79], hydrazine [80, 81] and primary amines [82]. The /f iminylphos-phine oxide formed in the reaction may serve as a Wittig reagent in the presence of a base to react with a ketone or an aldehyde leading to ,/fun saturated alkenyl-imines 153 (Scheme 10.74). The phosphorus group can be a phosphonium salt as well as a phosphonate. 

Aromatic carboxylic acids, a,/f-unsaturated carboxylic acids, their esters, amides, aldehydes and ketones, are prepared by the carbonylation of aryl halides and alkenyl halides. Pd, Rh, Fe, Ni and Co catalysts are used under different conditions. Among them, the Pd-catalysed carbonylations proceed conveniently under mild conditions in the presence of bases such as K2CO3 and Et3N. The extremely high toxicity of Ni(CO)4 almost prohibits the use of Ni catalysts in laboratories. The Pd-catalysed carbonylations are summarized in Scheme 3.9 [215], The reaction is explained by the oxidative addition of halides, and insertion of CO to form acylpalladium halides 440. Acids, esters, and amides are formed by the nucleophilic attack of water, alcohols and amines to 440. Transmetallation with hydrides and reductive elimination afford aldehydes 441. Ketones 442 are produced by transmetallation with alkylmetal reagents and reductive elimination. 

Asymmetric hydrogenation of either a carbonyl or an imino group to a hydroxyl group or an amino group has frequently been employed for the introduction of chirality in amino acid syntheses. Corey s catecolborane-oxazaborolidine protocol enables transformation of difluoromethyl ketone 1 into alcohol 2 with excellent enantioselectivity. The reaction of diastereoselective amination of a-hydroxyaldehyde 3 with A,A-diallylamine and 2-furyl-boronic acid provides furyl amino alcohol 4 in good chemical yield along with excellent diastereoselectivity. This protocol is applicable for the preparation of amino acids and amino alcohols with a trifluoromethyl group by the combination of /V,/V-diallyl or N,N-dibenzyl amine and aromatic, heteroaromatic and alkenyl boronic acids [7]. The usual chemical transformations as shown in steps 5 to 8 in Scheme 9.1 lead to (2S,3R) difluorothreonine 5 [8]. 

Trost et al. reported that the ruthenium-catalyzed reaction of the allenic alcohols and amines 234 with methyl vinyl ketone produced the 2-alkenyl heterocycles 235 in good to high yields (Scheme 76).149 This reaction proceeds via formation of the ruthenacycle 236, which could also exist as the jr-allyl species 237. 

The nitro group is a good leaving group, and allyl nitro compounds are used conveniently for allylation because they can be prepared easily by the reaction of nitromethane with aldehydes and ketones, and used for Pd-catalyzed reactions [15]. As an interesting application, the alkenyl triflate 30 was converted to the allyl nitro derivative 31, which was, without isolation, subjected to the Pd-catalyzed amination with 32 in the presence of tetramethylguanidine (TMG) as a strong amine base to afford the anri-MRS carbapenem intermediate 33 in 34% overall yield [16],... 

In a related work, a useful procedure for the synthesis of cyclohexenones was also developed by means of the reaction of ethyl benzoylacetate with methyl alkenyl ketones, using primary amine 129 as catalyst in this case. This reaction also consisted of a Michael/intramolecular aldol reaction sequence starting... 

There are many carbanion and ylid derivatives that also contain an acid moiety, an ester or an acid sutrogate. Ester and acid enolates, for example, react with a variety of electrophilic reagents to produce new acid or ester derivatives. If the electrophile contains an amine or an amine surrogate, amino acids are produced as the final product. In addition, ylids bearing an acid or ester moiety react with aldehydes or ketones bearing an amine moiety via a Wittig reaction or a Homer-Wadsworth-Emmons reaction to give alkenyl amino acids. 

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