Formamides reaction with alkenes

Nitroalkanes react with Jt-deficient alkenes, for example, p-nitro ketones are produced from a,P-unsaturated ketones [41], whereas allylic nitro compounds have been prepared via the Michael-type addition of nitroalkanes with electron-deficient alkynes (Table 6.19). The reaction in either dimethylsulphoxide [42] or dimethyl-formamide [43] is catalysed by potassium fluoride in the presence of benzyltriethyl-ammonium chloride the reaction with dimethyl acetylenedicarboxylate is only successful in dimethylsulphoxide [42], Primary nitroalkanes produce double Michael adducts [42,44], A-Protected a-aminoacetonitriles react with alkynes under catalysed solidiliquid conditions to produce the Michael adducts [45] which, upon treatment with aqueous copper(Il) sulphate, are converted into a,p-unsaturated ketones. 

Reactions with zinc were accomplished at room temperature, lower yields of difluorocyclopropanes resulted if solvents other than tetrahydrofuran (diethyl ether, acetonitrile, dimethyl-formamide) were utilized. Experimental data indicate that free carbene is generated by this method. Good yields of 1,1-difluorocyclopropanes were obtained with electron-rich alkenes. ... 

The Ritter reaction is a method for creating amides beginning with alkenes or alcohols (2° or 3°) and cyanide (Reddy, 2003). Preparation of a formamide is shown below ... 

Two reactions which should lend themselves to the synthesis of pyrrolidines with a wide variety of substituents have been published this year. In the first method Blake and co-workers have improved the versatility of a well known pyrrolidine synthesis from arylcyclopropyl ketones. By reaction with formamide in the presence of MgCl2, alkylcyclopropyl ketones (105) give good yields of pyrrolidines (106). The second method details the reaction of Schiff s bases of trimethylsilyl methylamine with acyl halides in the presence of alkenes and... 

The chain addition of formamide to alkenes is a closely related reaction. It results in the formation of primary amides. The reaction is carried out with irradiation in acetone. The photoexcited acetone initiates the chain reaction by abstracting hydrogen from formamide ... 

Formylation of alkenes can be accomplished with N-disubstituted formamides and POCl3. ° This is an aliphatic Vilsmeier reaction (see 11-15). Vilsmeier formylation can also be performed on the ot position of acetals and ketals, so that hydrolysis of the products gives keto aldehydes or dialdehydes ... 

Many carboxylic acids lose carbon dioxide on either direct or sensitized irradiation, and in some cases (4.10 the evidence points to the operation of an initial electron-transfer mechanism rather than primary a-deavage. Cleavage occurs readily with acyl halides, and this can [ead to overall decarbonylation (4.11). Aldehydes also cleave readily, since the (0=)C—H bond is more prone to homolysis than the (0= C-C bond. This offers a convenient method for replacing the aldehydic hydrogen by deuterium in aromatic aldehydes (4.12. and a similar initial reaction step accounts for the production of chain-Iengtheped amides when formamide is irradiated in the presence of a terminal alkene (4.13). 

Another relatively simple system for the epoxidation of tri- and c/r-disubstituted olefins is formamide-hydrogen peroxide in an aqueous medium. This reagent has the advantage of being pH-independent, which makes it attractive for biochemically mediated transformations. No reaction was observed in the case of /ran.v-disubstituted and terminal olefins. With bifunctional alkenes, the more reactive double bond is selectively epoxidized [95TL4015]. 

Since the amides (especially the formamides) are easily cleaved under hydrolysis conditions to amines, the Ritter reaction provides a method for achieving the conversions R OH R NH2 (see 10-32) and alkene R NH2 (see 15-8) in those cases where R can form a relatively stable carbocation. The reaction is especially useful for the preparation of tertiary alkyl amines because there are few alternate ways of preparing these compounds. The reaction can be extended to primary alcohols by treatment with triflic anhydride ° or Ph2CCl" SbClg or a similar salt in the presence of the nitrile. 

Many vinylogous amidinium salts, e.g. (185) and (186) (Scheme 25), are readily available by double formylation of CHa-acidic or alkenic compounds. Reviews on the chemistry of vinylogous amidinium salts are available. The first azavinylogous foimamidinium salt (187 Scheme 26) was prepared in 1960 by reaction of DMF with cyanuric chloride. The mechanism of this reaction has been estab-lished. Based on these findings new methods for the synthesis of these compounds were developed, e.g. the reaction of isocyanatomethyleneiminium salts with tertiary formamides affords salts (187). In the synthesis of the salts (187) cyanuric chloride can be replaced by phosphorus nitride chloride (PNCl2)3. ... 

In the laboratory of T.-L. Ho, the total synthesis of the novel marine sesquiterpene (+)-isocyanoallopupukeanane was completed." In the endgame of the synthesis, it was necessary to install the isocyano group onto the tricyclic trisubstituted alkene substrate so that it will occupy the more substituted carbon atom (according to Markovnikov s rule). The Ritter reaction was chosen to form the required carbon-nitrogen bond. The alkene substrate was dissolved in glacial acetic acid and first excess sodium cyanide followed by concentrated sulfuric acid was added at 0 °C. The reaction mixture was stirred at ambient temperature for one day and then was subjected to aqueous work-up. The product A/-alkyl formamide was subsequently dehydrated with tosyl chloride in pyridine to give rise to the desired tertiary isocyanide which indeed was identical with the natural product. 

Analogously to conventional reactions 201-203), bis(trimethylsiloxy) alkenes form heterocycles of different classes l,2-bis(trimethylsiloxy)-l-cyclohexene (305) reacts with formamide urea malodinitrile and ethyl (J-amino-crotonate to afford 4,5,6,7-tetrahydrobenzunidazole (309) ° 2-oxo-l, 3,4,5,6,7-hexahydrobenzimidazoIe (317) , 2-aniino-3-cyano-4,5,6,7-tetra-hydro-coumarone (312) and 2-methyl-3-ethoxy-carbonyl-4,5,6,7-tetrahydro-in-dole (373) respectively. 

These reactions are typified by Bredereck s formamide synthesis . This has been applied to the synthesis of 4,5-dimethylimidazole (as its formic acid complex) from acetoin and formamide <91JHC1819>. A similar reaction leads to 5-methylhistamine (243) <8lJHC83l>. 1-Hydroxyimidazoles are accessible in high yield from reaction of nitrosonium fluoroborate with acetonitrile and appropriate alkenes (Scheme 177) <84TL1319>. 

The Ritter reaction proceeds by a nucleophilic addition of hydrogen cyanide followed by the hydrolysis of the intermediate formamide. Higher tertiary alkyl amines are produced using the same method with higher alkenes and alcohol. This is considered the most practical way to produce tertiary amines [99]. 

The reaction is an equilibrium that can be shifted to the right by introduction of a base sodium acetate is one of the reagents of choice with branched olefins.4 For unbranched alkenes, dimethyl-formamide is preferred.5 Inorganic bases have also been used6 but are less satisfactory. Addition of copper(I) chloride7 improves the yields, since any Pd (II) that is reduced by the olefin (which in turn is converted into an aldehyde or ketone) is reoxidized. 

The reaction in Entry 12 is related and uses thioglycolate esters as a chain transfer agent. In this particular reaction involving an electron-rich alkene, the yield is only 8% in the absence of the thioglycolate. Entry 13 is another example of the addition of an acyl radical to relatively electrophilic alkene. Entry 14, involving the addition of formamide was done with acetone photosensitization. The 2-dioxolanyl radical involved in Entry 15 would be expected to be nucleophilic in character and higher yields were obtained with diethyl maleate than with typical terminal alkenes. The addition of 1,3-dioxolane to various enones has been done using benzophenone sensitization.The radicals in Entries 17 and 18 are electrophilic in character. Entries 19 and 20 are examples of thiol additions. 

As noted in the introduction to this section, under UV light irradiation, carbonyl groups [42] and alkenes [43] will add photochemically in a 2 + 2 sense across the 2- and 3-positions of indole, but only if an acyl or aroyl group is present on the indole nitrogen atom. The photocycloaddition reaction of carbonyl compounds with acylindoles was first reported by Julian and Tringham in 1973 [42], They found that irradiation of N-acetylindole or N-para-chlorobenzoylindole with benzophenone, benzoyl-formamide, or methyl benzoylformate gave oxetane products, as shown in Scheme 12. The stereochemistry of the products was not reported. No products were obtained when the indoles were irradiated with acetophenone, benzaldehyde, acetone, or propionaldehyde. This observation... 

The mechanisms of dehalogenations have been reviewed by Miller and in a series of papers , the stereoselectivity of the dehalogenation of the stilbene dibromides with a wide variety of reagents has been discussed. The meso-stilbene dibromide always eliminates to give the thermodynamically more stable alkene, namely tra 5-stilbene which is product of apparent a t/-elimina-tion. However, the J/-stilbene dibromide gives both cis- and rm i-stilbenes, and the ratio of these products can provide useful mechanistic information. One-electron reductants, such as chromous ion, give rise to intermediate radical formation in which rotation about the Ca-Cg bond allows thermodynamic control of the reaction. Two-electron reductants, such as iodide ion in dimethyl formamide, induce highly stereoselective a i-elimination. In protic solvents, carbonium ion intermediates were proposed to explain the trend towards thermodynamic control. Miller has proposed a reaction mechanism which embraces elimination, substitution, and electrophilic addition to alkenes. 

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