Ketenes enamine derivative

Dihydropyrans have been produced by the 1,3 cycloaddition of methyl vinyl ketone (77) or acrolein (29-J7) with enamines (see Section II.A.2). S-Lactones have been formed as a side product in the reaction of dimethyl ketene with enamines (77), and as the primary products in the reaction of excess ketene with enamines derived from ketones (75) (see Section II.A.4). 

C(R)=NR group with a nitrilium salt RCssNR .222 The acylation of the enamine can take place by the same mechanism as alkylation, but another mechanism is also possible, if the acyl halide has an a hydrogen and if a tertiary amine is present, as it often is (it is added to neutralize the HX given off). In this mechanism, the acyl halide is dehydrohalogenated by the tertiary amine, producing a ketene (7-14) which adds to the enamine to give a cyclobutanone (5-49). This compound can be cleaved in the solution to form the same acylated imine salt (27) that would form by the more direct mechanism, or it can be isolated (in the case of enamines derived from aldehydes), or it may cleave in other ways.223... 

The facile formation of cyclobutane products is indeed another important contribution of enamine chemistry (302-306). The formation of cyclobutanes has also been found in the closely related reactions of amino acetal derivatives of ketenes with acrylic esters (307). 

The intermediacy of ketenes in some enamine acylation reactions using acid chlorides was described above (386,387). Direct addition of ketene to enamines was studied simultaneously by several groups (414-420). The initially formed aminocyclobutanone products could be isolated in some instances, depending on the substitution of the initial enamine. Opening to give either the acylated enamine or the alternative vinylogous amide was found to occur spontaneously or on heating, particularly in adducts derived from enamines with an olefinic proton. 

On the other hand y-pyrones or 1,3-diketones could be obtained from the reactions of ketone derived enamines with diketene 423-426). The addition of dimethyl ketene dimer to aldehyde or ketone derived enamines produced cyclohexanediones 425,426). 

Attack on Unsaturated Carbon. The annual addition of phosphites to every variety of activated double bond continues. These include nitro-alkenes,9 a/S-unsaturated carboxylic acid derivatives,10 maleimides,11 fulvenes,12 and pyridinium salts.13 The reaction of diethyl phosphite with keten 0,N-, S,N, and Al,AT-acetals has been used to prepare the enamine phosphonates (19).14... 

A dissociative first step is anticipated exclusively in photolysis of the endo-cyclic enamide 181 (compare also 80 -a- 85 and 173 -> 174). The reaction is formulated through a ketene intermediate 182. The enamine 183 formed then undergoes hydrolysis to give the oxocarboxylic acid derivative 184 as the product. 

This topological rule readily explained the reaction product 211 (>90% stereoselectivity) of open-chain nitroolefins 209 with open-chain enamines 210. Seebach and Golinski have further pointed out that several condensation reactions can also be rationalized by using this approach (a) cyclopropane formation from olefin and carbene, (b) Wittig reaction with aldehydes yielding cis olefins, (c) trans-dialkyl oxirane from alkylidene triphenylarsane and aldehydes, (d) ketenes and cyclopentadiene 2+2-addition, le) (E)-silyl-nitronate and aldehydes, (f) syn and anti-Li and B-enolates of ketones, esters, amides and aldehydes, (g) Z-allylboranes and aldehydes, (h) E-alkyl-borane or E-allylchromium derivatives and aldehydes, (i) enamine from cyclohexanone and cinnamic aldehyde, (j) E-enamines and E-nitroolefins and finally, (k) enamines from cycloalkanones and styryl sulfone. 

Similar a,a -annulations were achieved from reaction of oc,/ -unsaturated acid chlorides with cyclic ketone enamines which afforded bicyclo[3.3.1]nonane-2,9-diones41,60 65 or bicyclo[4.3.1]decanones66. In this reaction, 7V-acylation of the enamine 109 occurs as the first step giving 110, followed by a [3,3] sigmatropic rearrangement to a ketene intermediate (111). Ketene 111 subsequently cyclized via 112 to a bicyclic immonium salt (113) which after hydrolysis gave the corresponding dione 11463. If there is an axially oriented electrophilic substituent at C-4 of the enamine (for example, R = COPh) the enolate anion 115 may cyclize to an adamantane derivative 116 (equation 20). 

The discovery by Stork and Borowitz and Opitz and Adolph that the addition of sulfenes (RCH=S02) to enamines gives good yields of 3-aminothietane-1,1-dioxides (e.g., 132) has been extensively exploited in the synthesis of a variety of thietane sulfone derivatives. Truce, Breiter, Abraham, and Norell at about the same time showed that sulfene can add to ketene acetals to give 3,3-dialkoxy substituted thietane 1,1-dioxides (e.g., 133). The sulfenes are generated by dehydrohalgenation of methanesulfonyl chlorides with triethylamine. [Attempts to add sulfines (e.g., PhCH=SO) to enamines to give thietane 1-oxides were not successful.1 Sulfene additions have been reviewed. ... 

Another classical approach to 3-carbolines involves Bischler-Napieralski reaction of indoles, the intramolecular cyclization of iminium chlorides derived from tryptamides. Triphenylphosphite proved to be a mild reagent capable of promoting this reaction <05SL661>. The cyclization of ketene iV,S-acetals derived from tryptamine produced push-pull P-carboline enamines <05SL309>. 

Diazonium Salts. Diazonium salts are potentially explosive. See the cautionary note in Experimental Conditions. Aryldiazonium salts 26 react with alkyl- and arylmagnesium reagents,184-191 arylzinc,190,192,193 and aryltin reagents194 to give azo compounds. Yields vary considerably the best are achieved with the diazonium salt 26e191 (see Eq. 48). Aryldiazonium salts also react with enolates, enol derivatives, or enamines of aldehydes (see Eq. 85),195 ketones (see Eq. 95),185 and with silyl ketene acetals (see Eq. 121).196,197... 

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