Chloroacylation

The first report of oxidative carbonylation is the reaction of alkenes with CO in benzene in the presence of PdCh to afford the /3-chloroacyl chloride 224[12,206]. The oxidative carbonylation of alkene in alcohol gives the q, f3-unsaturated ester 225 and /3-alkoxy ester 226 by monocarbonylation, and succinate 111 by dicarbonylation depending on the reaction conditions[207-209]. The scope of the reaction has been studied[210]. Succinate formation takes... 

The placement of a nitrogen atom directly on the benzilic carbon atom is apparently consistent with antispasmodic activity. Esterification of 2 (iV-piperidyl)ethanol by means of chloroacyl chloride (68) gives the basic ester (69). Displacement of the remaining halogen by piperidine gives dipiproverin (70). ... 

A radical cyclization of a 2-chloroacyl enamine 157 was used to synthesize 2-substituted pyroglutamates 160. Usually, the radical 158 undergoes an initial 5-endo cyclization (path a) and the resulting intermediate 159 attacked electrophiles like methyl acrylate to give the pyroglutamate 160. Unexpectedly, the reaction with methyl methacrylate took another course and a seven-membered... 

Abstract The use of A-heterocyclic carbene (NHC) complexes as homogeneous catalysts in addition reactions across carbon-carbon double and triple bonds and carbon-heteroatom double bonds is described. The discussion is focused on the description of the catalytic systems, their current mechanistic understanding and occasionally the relevant organometallic chemistry. The reaction types covered include hydrogenation, transfer hydrogenation, hydrosilylation, hydroboration and diboration, hydroamination, hydrothiolation, hydration, hydroarylation, allylic substitution, addition, chloroesterification and chloroacylation. 

Chloroacylation of terminal aryl, alkyl or alkenyl alkynes [Le. the addition of RC(=0)-C1 across the CC triple bond] with aromatic acyl chlorides was catalysed by [IrCl(cod)(lPr)] (5 mol%) in good conversions (70-94%) in toluene (90°C, 20 h). Z-addition products were observed only, hitemal alkynes were umeactive. Surprisingly, a phosphine/[lr(p-Cl)(l,5-cod)]2 system under the same conditions provides decarbonylation products (Scheme 2.34) [117]. 

Scheme 2.34 Chloroacylation of alkynes catalysed by iridium NHC complexes...

Bicyclic alkaloids. Nagao et al. have developed a general synthesis of chiral bicyclic alkaloids with a nitrogen atom at the ring juncture, such as pyrrolizidines [5.5], quinolizidines [6.6], and indolizidines [6.5], based on a highly diastereose-lective alkylation of 3-a>-chloroacyl-(4S)-isopropyl-l,3-thiazolidine-2-thiones (1, m = 1,2) with 5-acetoxy-2-pyrrolidinone (2, n = 1) or 6-acetoxy-2-piperidinone (2, n = 2). Thus the tin enolate of 1 (m = 1), prepared with Sn(OTf) and N-... 

An S-acetylated 2-aminothiol was reacted with 2-chloroacyl chlorides (Equation 85) <1989JPS937>. The reactions of 2-aminoethanethiol with 2,3-butanedione <1998JFA2278>, alkynyl cyanide 279 <1993TL5681>, and cyclic hemiacylal 281 <1992FI(34)2131> are shown in Scheme 59. Mechanisms for the formation of products 277, 278, and 280 were suggested, but not however for the unexpected product from 281. 

Carbonylation-Decarbonylation. These reactions constitute a large and important segment of the homogeneous catalytic literature. Catalysis by most of the group VIII noble metals has been found, and a variety of substrates have been converted. For example, olefins react with CO and PdCl2 or (< 3P)2PdCl2 to yield -chloroacyl chlorides (58) and unsaturated acyl chlorides (59), respectively, a, w-Dienes, such as... 

Chlorine may be placed on the a-carbon of a side chain on the oxadiazole ring by allowing an amidoxime to react with an a-chloroacyl chloride.11,37 The chloromethyl group in 64 has reactivity of the order of... 

Oxalyl chloride yields COCl radicals on photolysis and this reaction has been used to directly substitute alkanes with the chloroacyl group (equation 30). Similarly, biacetyl reacts with alkanes in a benzoyl peroxide-initiated chain reaction to give ketones in ca. 60-70% yield (equation Cyanogen... 

Some other olefins are carbonylated similarly carbon monoxide is introduced at the terminal position to form )3-chloroacyl halides (10). In addition, it was found that metallic palladium is a versatile catalyst for carbonylating various olefins. Saturated esters are prepared by carbonylating simple a-olefins and some cyclic olefins when the reaction is carried out in alcohol containing hydrogen halide and a catalytic amount... 

The following mechanism was proposed for the carbonylation of olefin-palladium chloride complex (10). The first step is coordination of carbon monoxide to the complex. Insertion of the coordinated olefin into the palladium-chlorine bond then forms a -chloroalkylpalladium complex (IV). This complex undergoes carbon monoxide insertion to form an acylpalladium complex (V), as has been assumed for many metal carbonyl-catalyzed carbonylation reactions. The final step is formation of a )8-chloroacyl chloride and zero-valent palladium by combination of the acyl group with the coordinated chlorine. 

The similarity in the mechanisms of the two carbonylations is apparent. In the / -chloroacyl chloride formation, the first step is the insertion of olefins into the palladium-chlorine bond. For the catalytic carbonylations, the insertion of olefins takes place to the palladium hydride complex formed in situ. In both cases, divalent palladiums react with olefins. 

The overall reaction and product stoichiometries for the degradation of chloroalkene substrates by O2 - in DMF are summarized in Table 7-1.20 Within the limits of a reaction time of 10 min or less, chloroethene, frflws-1,2-dichloroethene, Aldrin, and Dieldrin are not oxidized by O2 - in DMF. A reasonable mechanism for these oxidations is an initial nucleophilic addition of superoxide to the chloroalkenes [e.g., tetrachloroethene (Scheme (7-7)]. Subsequent loss of chloride ion would give a vinyl peroxy radical, which can cyclize and decompose to a chloroacyl radical and phosgene. t These would undergo subsequent facile reactions with O2 - to give bicarbonate and chloride ions. 

In contrast to the behavior of (chloroacyl)- and (bromoacyl)silanes, which react according to the Perkow rearrangement, the corresponding iodoacylsilane reacts ahnost completely with trimethyl phosphite in a Michael-Arbuzov reaction to afford dimethyl 2-(fcrt-butyldimethylsilyl)-2-oxoethylphosphonate in 96% yield. - ... 

It is possible to directly chloroacylate an aniline using chloroacetonitrile and boron trifluoride, ortho to the nitrogen. After (V-acylation, ring closure produces iV-acetyl-indoxyls. The Sugasawa synthesis of indoles utilises these same orf/to-chloroacetyl-anilines, via borohydride reduction and ring closure. ... 

If nucleophilic attack is slowed down by steric hindrance, for example in the formation of a trans decalin system (Table 13, entry 17)14, stereoscrambling can occur but otherwise complete retention of configuration is observed (Table 13, entries 15, 16 and 18). The starting material is readily available by palladium-catalyzed 1,4-chloroacylation of 1,3-dienes followed by chemo- and stereoselective substitution of the allylic chloride. 

Sulfuryl chloride, in the presence of an organic peroxide, can also be effectively used for the preparation of chloroaliphatic carboxylic acids, their alkyl esters, and chloroacyl halides. 

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