Lactams enamines, cyclic

Phosphorus-containing enamines have been prepared by phosphorylation of N-vinyl substituted tertiary amides, lactams and cyclic imides with phosphorus pentachloride ". Addition of amines to diphosphoryl alkynes has been described. Addition of RR NH [R = H, Ri = Me, cyclohexyl, PhCH2 RR = (CHj) to (Et0)2P(0)C=CP(0K0Et2)2 in CH2CI2 at 25 °C gave 93-100% of (Et0)2P(0)C(NRRi)=CHP(0)(0Et2)2 . Speziale and coworkers have studied the reactions of phosphorus compounds with trichloroacetamides. 

Cyclic enamines with an isomeric position of the double bond have been obtained by the addition of Grignard reagents to five- (78-81), six- (82-86), seven- (87-90), and thirteen- (89-91) membered lactams, whereas other medium-sized (92,93) lactams furnished amino ketones. The reaction has been extended to substituted lactams (94-98), and iminoethers (99,100). 

Radical cyclization is compatible with the presence of other functional groups. Treatment of XCH2CON(R)-C(R )=CH2 derivatives (X = Cl, Br, 1) with Ph3SnH and AIBN led to formation of a lactam via radical cyclization. " Cyclization of N-iodoethyl-5-vinyl-2-pyrrolidinone led to the corresponding bicyclic lactam, " and there are other examples of radical cyclization with molecules containing a lactam unit " or an amide unit. Radical cyclization occurs with enamines as well. Photochemical irradiation of A,A-dialIyl acrylamide leads to formation of a lactam ring, and in this case thiophenol was added to generate the phenylthio derivative. Phenylseleno N-allylamines lead to cyclic amines. co-Iodo acrylate esters cyclize to form lactones. " ... 

The use of cycloadditions for synthesizing medium-sized ring lactams is more or less restricted to the generation of seven-membered rings. The simplest method to generate azepinones seems to be the [6-1-1] reaction of a 1,6-dicar-boxylic acid chloride 148/152 and a phosphinimine 149, the in situ formed chloro enamine 150 underwent a Chapman rearrangement to give a cyclic imide 151/153 (Scheme 28)] [36]. 

Lactams with larger rings, e.g. seven-,143,144 eight-,145 nine-,148 eleven-, and thirteen-membered lactams,147 yield acyclic amino-ketones as the sole products, as is to be expected. With the seven- and thirteen-membered rings, the existence of both forms might be expected, and the salts of 1-methyl-2-a-naphthyl-l-aza-2-cycloheptene and l-methyl-2-a-naphthyl-l-aza-2-cyclotridecene have been prepared in both the cyclic enamine and the acyclic amino-ketone forms.148 The structure of the products also depends upon the Grignard reagent used. 

Oxidation of cyclic enamins or unsaturated lactams, corresponding to the cyclic enol ethers, led to oxolactams and oxoimides, respectively [105]. 

Treatment of a thirteen-membered lactam with 1-naphthylmagnesium bromide forms both a cyclic enamine and the amino ketone412. Imides of dicarboxylic acids produce with organometallic reagents cyclic enamino compounds such as 108 (n = 1, 2)413-418. 

A case is reported164 (Scheme 115) in which a cyclic enamide was reduced at the carbonyl group by LiAlH4 as it was for lactams and amides, leaving untouched the enamine function. 

In addition to several general reviews on enamine chemistry, all of which include heterocyclic syntheses, there is an extensive survey by Hickmott which is entirely concerned with the formation of heterocycles. More specialized reviews deal with heterocyclic enamines, enaminones, the photochemistry of enamides , heterocyclic jS-enamino esters , enamino thiones , the synthesis of indole alkaloids via enamines , formation of pyrimidines, pyridopyrimidines, pyridines and pyrrolizines from enamines , synthesis of lactams , formation of heterocycles from cyclic enamino ketones and 2-acetylcyclohexen-l-ones, the synthesis of 3-cyano-2(l -pyrimidine-thiones and -selenones from jS-enamino ketones and the chemistry of cyclic en-aminonitriles. ... 

Cyclic ketoimides Ozonization of cycUc enamine lactams (1) is a route to medium and macrocyclic ketoimides (2). Yields are lower if m-chloroperbenzoic acid is used. However, this peracid is preferable to ozone for oxidation of N-acetyl enamines of type (3). 

The Bode group disclosed NHC-catalyzed highly enantioselective annulations of a,P,P -trisubstituted enals with cyclic sulfonylimines. Mechanistically, it is proposed that the combination of enal and free NHC leads to the formation of the Breslow intermediate, which is oxidized to form the key a,p-unsaturated acyl azolium. Tautomerization between the imine and the enamine occurs readily in the presence of base, and the enamine is intercepted by the key a,p-unsaturated acyl azolium to form a hemiaminal which further engages in a Stork-Hickmott-Stille-type annulation via a tight-ion-pair/aza-Claisen type transition state. Lactam formation follows the protonation of enolate and brings about catalyst turnover to complete the catalytic cycle (Scheme 7.113). 

The addition of ketens or keten precursors to cyclic imines to form /3-lactams has been known for some time and has been reviewed in two monographs. Using this method, Bose and co-workers were able to synthesize epi-penicillins in very few steps. The addition is successful with thioimidates " " and dithioimidates such as (146), from which (147) can be obtained. However, when imine-enamine tautomerism is possible [e.g. (148)], the reaction fails and the acylenamine (149) is formed in... 

Synthesis of enamines from carboxylic acid amides via 1-alkoxyazomethinium salts and amide acetals Cyclic enamines via lactam acetals... 

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