Amides nitrile ylides

Reaction of iV-[(benzotriazol-l-yl)methyl]amide 707 with PCI5 gives chloroimine 708, which upon treatment with Bu OK is converted to nitrile ylide 709. Benzyl esters of ot,(3-unsaturated acids used as dipolarophiles trap species 709 to generate pyrroles 712 (Scheme 110) <2002JHC759>. When no trapping agent is added, the N-2 atom of benzotriazole act as a nucleophile, and tricyclic system 711 is formed <2001TL9109>. Addition of benzyl bromide... 

This method has been used extensively for the generation of diene- and triene-conjugated nitrile ylides (see Section 7.4.1.2) using strong bases. Potasium tert-butoxide (58) was used for the most part but in recent work (59,60) it was reported that lithium bisftrimethylsilyl)amide is both more effective and more convenient. It has also been shown that thermally unstable imidoyl chlorides for use in these reactions can be prepared by reaction of the corresponding amides with chlorodi-methylformiminium chloride at 0 °C, a reaction that is more effective than using either thionyl chloride or phosphoms pentachloride at higher temperatures (61). 

The nitrile ylides were generated from amides via the imidoyl chloride-base method and hence the reaction is, overall, the electrocyclic equivalent of a Bischler-Napieralski type of process. However, it has the advantage that it is effective for cyclization on to both electron-rich and electron-poor aromatic rings, unlike the Bischler-Napieralski reaction itself, which is an electrophihc process and only works well for electron-rich rings. 

Cyclization of the nitrile ylide generated from amide (150a) via an imidoyl chloride led to an 18% yield of a fused tricyclic pyrrole (Scheme 46).77 Similarly, the nitrile ylide derived from (150b) cyclized in 6% yield. 

Keywords oxime, Beckmann rearrangement, nitrile ylide, amide... 

Ylides can cyclopropanate unsaturated systems which are susceptible to Michael additions, i.e. a,jS-unsaturated ketones, esters, amides, nitriles, sulfones, sulfonamides, and nitro compounds. Enhancement of electron withdrawal from the carbon-carbon double bond facilitates the reaction. The reaction is non-stereospecific. The intermediacy of zwitterions has generally been accepted, and hence the stereochemistry of the product may be predictable on the basis of the stepwise mechanism. Namely, the Michael addition of the ylide will occur predominantly from the less hindered side of the double bond in a given molecule and the subsequent cyclization will take place in the conformation which minimizes the non-bonded repulsions. 

Syntheses in which a nitrile provides atoms 1 and 2 start from an ylide (82JFC373), or a 1-amino-2-pyridone (82S974) to give compounds 45 and 46. Other two atom fragments used with l-amino-2-pyridones are amides which give compounds such as 47 (86S860). 

The addition reaction of enolates and enols with carbonyl compounds is of broad scope and of great synthetic importance. Essentially all of the stabilized carbanions mentioned in Section 1.1 are capable of adding to carbonyl groups, in what is known as the generalized aldol reaction. Enolates of aldehydes, ketones, esters, and amides, the carbanions of nitriles and nitro compounds, as well as phosphoms- and sulfur-stabilized carbanions and ylides undergo this reaction. In the next section we emphasize the fundamental regiochemical and stereochemical aspects of the reactions of ketones and aldehydes. 

The second class of benzo-fused heterocycles accessible from benzofuroxans are benzimidazole oxides. In this case only one carbon from the co-reactant is incorporated in the product. With primary nitroalkanes 2-substituted l-hydroxybenzimidazole-3-oxides (46) are formed via displacement of nitrite, and / -sulfones behave similarly. The nitrile group of a-cyanoacetamides is likewise eliminated to alford 2-amide derivatives (46 R = CONRjX and the corresponding esters are formed in addition to the expected quinoxaline dioxides from acetoacetate esters. Under similar conditions secondary nitroalkyl compounds afford 2,2-disubstituted 2//-benzimidazole-1,3-dioxides (47). Benzimidazoles can also result from reaction of benzofuroxans with phosphorus ylides <86T3631>, nitrones (85H(23)1625>, and diazo compounds <75TL3577>. 

Phenyl-l,3,4-oxathiazol-2-one (370), prepared from primary amides and tri-chloromethanesulfenyl chloride, undergoes a ready thermal elimination of carbon dioxide with the formation of the nitrile sulfide ylide (371). This can be trapped by a wide variety of unsaturated dipolarophiles, and with an alkyne provides a ready route to isothiazoles (372) (see Chapter 4.17). Applications to 1,2,4-thiadiazole synthesis are described in Chapter 4.25. Thermolysis of l,3,4-oxadiazolin-5-ones (500 C/10 mmHg) results in the loss of CO2 and generation of the corresponding nitrilimine (78JOC2037). 

Along with carbonyl stabilized Wittig reagents, other stabilized ylides have also been used to prepare unsaturated nitrile (eq 70) and Weinreb amide (eq 71) adducts. 

An unprecedented protocol for the stereoselective synthesis of stracturally diverse electron-deflcient alkenes in moderate to excellent yields from readily accessible A-sulfonyl imines and stabilized phosphonium ylides has been reported. The oleflna-tion reaction of (V-sulfonyl imines with nitrile-stabilized phosphonium ylides affords an array of a./S-unsaturated nitriles with high Z selectivity, and the reactions with ester-, amide-, and ketone-stabilized phosphonium ylides afford a,)3-unsaturated esters, amides, and ketones with high E selectivity, respectively (Scheme 3). 

The addition of aryl azides to a-cyanoacrylic esters, nitriles, and amides, leads in each case to a pyrrolidine (94). The postulated mechanism involves the expected triazoline intermediate (95) which gives the ylide (96) followed by a second cycloaddition. 

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