Amides synthesis from alkenes

Azetidin-2-ones are more reactive than y- and <5-lactams because of ring strain. This is true for the alkaline fission to give salts of / amino carboxylic acids, as well as for the acid-catalysed hydrolysis to fi-carboxyethylammonium salts. Starting from alkenes and chlorosulfonyl isocyanate, a stereocontrolled synthesis of / -amino carboxylic acids can be realized. Ammonia and amines react with azetidin-2-ones, also with ring-opening, to produce / -amino carboxylic amides. Hence they are acylated by azetidin-2-ones ... 

Carbon-Oxygen Bond Formation. CAN is an efficient reagent for the conversion of epoxides into /3-nitrato alcohols. 1,2-cA-Diols can be prepared from alkenes by reaction with CAN/I2 followed by hydrolysis with KOH. Of particular interest is the high-yield synthesis of various a-hydroxy ketones and a-amino ketones from oxiranes and aziridines, respectively. The reactions are operated under mild conditions with the use of NBS and a catalytic amount of CAN as the reagents (eq 25). In another case, N-(silylmethyl)amides can be converted to A-(methoxymethyl)amides by CAN in methanol (eq 26). This chemistry has found application in the removal of electroauxiliaries from peptide substrates. Other CAN-mediated C-0 bondforming reactions include the oxidative rearrangement of aryl cyclobutanes and oxetanes, the conversion of allylic and tertiary benzylic alcohols into their corresponding ethers, and the alkoxylation of cephem sulfoxides at the position a to the ester moiety. 

Butylation of phenylacetonitrile with aqueous NaOH, as shown in Scheme 25, proceeds faster by use of high DF (>0.5) anion exchange resins.The strongly alkaline conditions degrade the quaternary ammonium ions of the catalyst. Catalyst (64) (1% DVB) is active for alkylation of phenylacetonitrile and benzyl phenyl ketone, and for Williamson ether synthesis, and it is much more stable in base than AERs. AERs in OH form are catalysts for dichlorocyclopropane syntheses from alkenes, chloroform and solid sodium hydroxide, and for dehydration of amides to nitriles. AERs in the appropriate hydroxide, acetate, or cyanide form are catalysts for aldol condensations, Michael reactions, Knoevenagel condensations, cyanoethylations and cyanohydrin syntheses. " ... 

Alkenes can add to double bonds in a reaction different from those discussed in 15-19, which, however, is still formally the addition of RH to a double bond. This is called the ene reaction or the ene synthesis For the reaction to proceed without a catalyst, one of the components must be a reactive dienophile (see 15-58 for a definition of this word) such as maleic anhydride, but the other (which supplies the hydrogen) may be a simple alkene such as propene. Cyclopropene has also been used. ° The reaction is compatible with a variety of functional groups that can be appended to the ene and dienophile. N,N-Diallyl amides give an ene cyclization. 

Applications of the cross-metathesis reaction in more diverse areas of organic chemistry are beginning to appear in the literature. For example, the use of alkene metathesis in solution-phase combinatorial synthesis was recently reported by Boger and co-workers [45]. They assembled a chemical library of 600 compounds 27 (including cisttrans isomers) in which the final reaction was the metathesis of a mixture of 24 oo-alkene carboxamides 26 (prepared from six ami-nodiacetamides, with differing amide groups, each functionalised with four to-alkene carboxylic acids) (Eq.27). 

P. Wipf, T.C. Henninger, Solid-phase synthesis of peptide mimetics with ( )-alkene amide bond replacements derived from alkenylaziridines, J. Org. Chem. 62 (1997) 1586-1587. 

The amidoalkylation of alkenes is a versatile process that is often applied for the synthesis of 5,6-dihydro-4/7-l,3-oxazines <1996CHEC-II(6)301, 1998T1013>. In a recent version of this reaction, T-acyliminium ions were generated from Y-(benzotriazol-l-ylmethyl)amides in the presence of zinc bromide <2001J(P2)530>. 

The N-heterocyclic alkenes derived from ring-closing metathesis are useful substrates for further transformation. In a synthesis directed toward the insecticidal cripowellin 12, Dieter Enders of RWTH Aachen has shown (Angew. Chem. Int. Ed. 2005,44, 3766) that the tertiary amide 8 cyclizes efficiently to the nine-membered alkene 9. The vision was that an intramolecular Heck cyclization could then deliver the cripowellin skeleton. Indeed, the Heck did proceed, and, depending on conditions, could be directed toward either 10 or 11. Unfortunately, the conformation of 9 is such that the cyclization proceeded cleanly across the undesired face. Nevertheless, both 10 and 11 appear to be valuable intermediates for further transformation. 

On the pages which follow, general methods are illustrated for the synthesis of a wide variety of classes of organic compounds including acyl isocyanates (from amides and oxalyl chloride p. 16), epoxides (from reductive coupling of aromatic aldehydes by hexamethylphosphorous triamide p. 31), a-fluoro acids (from 1-alkenes p. 37), 0-lactams (from olefins and chlorosulfonyl isocyanate p. 51), 1 y3,5-triketones (from dianions of 1,3-diketones and esters p. 57), sulfinate esters (from disulfides, alcohols, and lead tetraacetate p. 62), carboxylic acids (from carbonylation of alcohols or olefins via carbonium-ion intermediates p. 72), sulfoxides (from sulfides and sodium periodate p. 78), carbazoles... 

A large part of the usefulness of the Michael reaction in organic synthesis derives from the fact that almost any activated alkene can serve as an acceptor7—a, 3-unsaturated ketones, esters, aldehydes, amides, acids, lactones, nitriles, sulfoxides, sulfones, nitro compounds, phosphonates, phosphoranes, quinones,... 

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