Acid chlorides dehydrohalogenation

The first /3 -lactam was produced by addition of a ketene to an imine and there are now many examples of this type of approach. The ketenes are most frequently generated in situ from acid chlorides by dehydrohalogenation, but have also been produced from diazo ketones, by heating of alkoxyacetylenes and in the case of certain cyanoketenes by thermolysis of the cyclic precursors (162) and (163). 

Triethylamine has been found to dehydrohalogenate acid chlorides having a-hydrogens to give ketenes according to the reaction. In an interesting variation on this... 

The cycloaddition of a series of reactive haloketenes with tetramethylallene has been investigated.9 The ketencs were generated by triethylamine dehydrohalogenation of the corresponding acid chlorides in the presence of excess atlene. 

Ketene reactivity in intramolecular cycloadditions parallel those in intermolecular reactions in which chloro-, vinyl-, aryl- and alkoxyketenes are more reactive than the alkylketenes. In most instances the ketene is generated by amine dehydrohalogenation of an acid chloride. There are, however, a few examples of ketenes prepared along less conventional routes as by the examples for the formation of 11.150 12,151 and 13.151... 

The synthesis of chlorocyanoketene presented here has advantages over other routes such as dehydrohalogenation of the appropriate acid chloride.5 The most obvious advantage is that the ketene is generated slowly during thermolysis. Thus, its concentration is always low. In addition, since it is generated by pyrolytic means, the presence of tert-amines and/or metals is avoided. No other method for the synthesis of chlorocyanoketene has been reported. However, we have found that it can be prepared with difficulty from chlorocyanoacetyl chloride. 

Such ring closures have been effected by a variety of methods generally involving either the direct cyclodehydration of the acids or the cyclo-dehydrohalogenation of the acid chlorides by an intramolecular Friedel-... 

Ketenes and derived products. Triethylamine dehydrohalogenates an acid chloride having an a-hydrogen atom to give a ketene isolable as the ketene dimer, which can be converted into a j8-ketoacid or a symmetrical ketone (Sauer An example is the preparation of laurone from lauroyl chloride. An ethereal solution of the acid... 

Cycloaddition of vinylketenes, produced in situ from the dehydrohalogenation of appropriately substituted unsaturated acid chlorides, with alkenes provides a convenient source of 2-vinyl-cyclobutanones. Oxidation with ruthenium(III) chloride trihydrate gave the corresponding P-oxo acid, which by treatment with oxalyl chloride and diazomethane, successively, led to the desired 2-(2-diazoacetyl)cyclobutanones. These diazo ketones are thermally labile and rearrange upon brief heating in refluxing xylene to give the spiro[cyclopropane-l,5 -furan-2 (5 i/)-ones] 2 (Table 2). ... 

Modified Darzens reaction. The original Darzens synthesis of u./3-unxaturated ketones3 involved the addition of acid chlorides to cyclohexenes in the presence of aluminum chloride or stannic chloride followed by dehydrohalogenation. For example, the addition of acetyl chloride to cyclohexene affords l-acetyl-2-chlorocyclohexane, which on dehydrohalogenation (dimethylaniline) gives methyl cyclohexenyl ketone. 

A 1-endo reaction forming a Prins-type product has been described43. The cyclization of acid chloride 19 leads to a mixture of the chlorides 20 a consecutive dehydrohalogenation results in the cycloheptenone 21 in about 67% overall yield. 

An alternative method of preparing ketenes is to dehydrohalogenate acid chlorides by tertiary amines. 

Benzoyl quinidine (BQ) (3) catalysed p-lactam synthesis from acid chloride and tosyl imine, as reported by Taggi et al. [23]. In this reaction, ketene generated from the acid chloride with BQ (3) via dehydrohalogenation reacted with imine to give cw-p-lactam selectively with quite high ee (Table 8.3). The BQ (3)-HCl was regenerated to BQ (3) with Proton Sponge (1). 

The Inifer process developed by Kennedy can be used to functionalize vinyl monomers via a cationic route by initiating a polymerization with an alkyl halide-boron trichloride mixture R BCl. The termination by transfer to an alkyl halide leaves a halide-terminated polymer. This can be transformed to a hydroxyl terminal unit via the sequence (1) dehydrohalogenation, (2) hydroboration, and (3) oxidation and hydrolysis (Equation 5.24). These co-functional blocks may be coupled to form diblock copolymers using standard reaction techniques, e.g., diisocyanate will couple cohydroxy and co-amine blocks together. Direct reactions can also occur, and co-acid chlorides combine readily with co-hydroxy units. 

Peters and co-workers developed a tertiary amine-catalyzed enantioselective [4+2] cycloaddition of a,p-unsaturated acid chlorides 76a-e and electron-poor aldehyde chloral (77) to provide 5-lactones 79a-e, Scheme 3.27 [42], Vinylketene, which was formed in situ by dehydrohalogenation of a,p-unsaturated acid chloride... 

Mixed dimers are obtained in good yield by the generation of two different ketens in situ by dehydrohalogenation of acid chlorides. These cross-additions lead regio-... 

Preparative Methods conveniently prepared as outlined in eq 1. Treatment of l-(trimethylsilyl)propyne (2) with 1.1 equiv of diisobutylaluminum hydride (25 °C, 21 h) and 1.1 equiv of methyllithium (0 °C, 0.5 h) in ether-hexane, followed by reaction of the resulting vinylalanate with anhydrous carbon dioxide, yields (Z)-2-(trimethylsilyl)-2-butenoic acid (3) in 68% yield. Exposure of the potassium salt of this acid (4) to 1.1 equiv of oxalyl chloride in pentane containing a catalytic amount of iVW-dimethylfonnamide (0-25 °C, 1.5 h) then produced a mixture of the acid chloride (5) and its geometric isomer, which was dehydrohalogenated without further purification. A solution of (5) in pentane was added dropwise over 1-2 h to a solution of 0.9 equiv of triethylamine in pentane... 

One of the oldest methods of preparing diphenylketene consists in the dehydrohalogenation of diphenylacetyl chloride with tertiary amines. The yield of the ketene was reported as quantitative when tripropylamine was the dehydrohalogenating agent, and considerably less with quinoline, whereas thermal dehydrohalogenation of the acid chloride... 

Polymeric amines can be proton acceptors, acyl transfer agents, or ligands for metal ions. The 2- and 4-isomers of poly(vinylpyridine) (11) and (12) and the weakly basic ion exchange resins, p-dimethylaminomethylated PS (2) and poly(2-dimethylaminoethyl acrylate), are commercial. The ion exchange resins are catalysts for aldol condensations, Knoevenagel condensations, Perkin reactions, cyanohydrin formation and redistributions of chlorosilanes. " The poly(vinylpyridine)s have been used in stoichiometric amounts for preparation of esters from acid chlorides and alcohols, and for preparation of trimethylsilyl ethers and trimethylsilylamines from chlorotrimethylsilane and alcohols or amines. Polymer-suppored DBU (l,8-diazabicyclo[5.4.0]undec-7-ene) (52) in stoichiometric amounts promotes dehydrohalogenation of alkyl bromides and esterification of carboxylic acids with alkyl halides. The protonated tertiary amine resins are converted to free base form by treatment with aqueous sodium hydroxide. 

Staudinger and Klever first noted the propensity for selfcondensation reactions in their landmark series of publications on the structure and reactivity of ketenes [48]. However, it was not until almost half a century later that Sauer undertook more exhaustive studies into the dimerization of ketenes via tertiary amine mediated dehydrohalogenation of acid chlorides [49]. While Sauer s studies represent a... 

The literature in the field of controlled ketene cross-dimerization is relatively sparse, with the lack of suitable catalysts to preferentially enable heterodimerization as opposed to homodimerization a recurring problem in establishing a useful synthetic protocol. Sporadic reports of controlled heterodimerization of unusual ketene classes exist in the literature, but are limited to halogenated [64] and cyano-ketenes [65]. Nevertheless, the laboratory of Romo was able to successfully dehydrohalogenate acid chlorides to generate racemic ketene heterodimers used as intermediates in the preparation of salinosporamide A and cinnabaramide A [42b]. 

Two syntheses of the trail pheromone, neocembrene (435), of Nasu-titermes spp. termites have been reported. Kodama et al. 185) (Scheme 78) prepared the allylic phenyl thioether (430) from trans,trans-gQX iny linalool (429). Terminal epoxidation of (430) followed by intromolecular cyclization, desulfurization, and dehydration led to (435). Kitahara et al. 186) cyclized fra 5-geranylgeranic acid chloride (436) with SnCU to afford chloroketone (437) (Scheme 79). Dehydrohalogenation of (437) and subsequent reduction of ketone (438) via acetate (441) gave neocembrene (435). 

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