A,3-Unsaturated acyl chlorides

Reaction of the enamino ester 224 with a,/3-unsaturated acyl chlorides 222 or anhydride 223 in boiling THF gave 4-phenyl-l,6-dioxo-l,3,4,6,7,8-hexahydropyrido-[2,l-c][l,4]oxazine-9-carboxylates (225) (95TL1657 ... 

Acyl-ylides, e.g. (58), prepared from a)3-unsaturated acyl chlorides and ethoxy-carbonylmethylenetriphenylphosphorane, undergo Michael addition reactions with... 

Unusual Friedel-Crafts reactions, IX. One-step ortho-acylation of phenols with a,(3-unsaturated acyl chlorides. Synthesis of 2 -hydroxychalcones and sorbicillin analogues. Tetrahedron 40 4081-4084. 

Acylation takes place similarly with a,/3-unsaturated acid chlorides such as 92 (260) and with ethylmalonyl chloride (93) (130) (Scheme 65). 

There are three possible active sites in a,(3-unsaturated acylzirconocene chlorides with respect to nucleophiles, namely the (3-unsaturated carbon, the acyl carbon, and the Zr—chlorine bond. The reactions of a, (3-unsaturated acylzirconocene chlorides with nucleophiles indicate bimodal reactivity (nucleophilic or electrophilic) at both the acyl and P-carbons (Scheme 5.37) [40],... 

Two papers describing the intramolecular ene cyclization for the preparation of C6 functionalized pteridines has appeared. Thus 4-amino-5-nitrosopyrimidines such as 249 reacted with a,/3-unsaturated acid chlorides acylating at the 6-amino group group to afford nitrosoamides 250 which on thermolysis in toluene underwent the pericyclic cyclization and subsequent loss of water to afford a mixture of the E- and Z-isomers of the 6-oxopteridine 251 in good yield <2006HCA1140, 2007HCA521>. 

Cyclohexane can be acylated with acetyl chloride and AICI3 to yield l-acetyl-2-methylcyclopentene in 37% yield.127 Alkanes, such as 2-methylbutane, cyclohexane, methylcyclopentane, and methylcyclohexane, are easily acylated with a,p-unsaturated acyl chlorides in the presence of A1C13 and a hydride acceptor to afford mono- or bicyclic products after secondary transformations.128 Isoalkanes (isopentane, 2-methylpentane, 3-methylpentane, 2,3-dimethylbutane) undergo diacylation and eventually form pyrilium salts under Friedel-Crafts acylation conditions with acetyl chloride or acetic anhydride.129... 

In another simple procedure, deprotonation of methoxy bis(trimethylsilyl)methane with butyl lithium and addition of the resulting anion to aldehydes induces Peterson elimination (Scheme 27). The product methyl enol ethers could be hydrolysed to the parent acyl silanes with hydrochloric acid-THF or could be treated with electrophiles such as M-halosuccinimides to give a-haloacyl silanes105. Alternatively, treatment with phenyl selenenyl chloride, oxidation at selenium and selenoxide elimination afforded a,/3-unsaturated acyl silanes. 

Acyclic a,/3-unsaturated acid chlorides do not undergo this acylation. However, cyclic vinylsilanes also undergo Friedel-Crafts acylation with a,/S-unsaturated acid chlorides to give dienones of type a, which are cyciized by SnCl to cyclopentenones. A typical example is formulated for the reaction of 5-methyl-l-tri-methylsilylcyclopentene (3) with j3,iS-dimethylacryloyl chloride. The first step is conducted with AICI3 and gives 4, which after isolation is cyciized with SnCU to a mixture of 5 and 6. The cyclopentenone 6 is obtained in 55% overall yield after isomerization with RhCU. 

Acylations by a,3-unsaturated acyl halides provide routes to a,3,a, 3 -unsaturated ketones. Care must be taken in choice of reaction conditions, since Lewis acids are excellent catalysts for Nazarov cy-clizations to cyclopentenones (Scheme 2). Indeed, this can be exploited as a synthesis of the five-mem-bered ketones without isolation of the intermediate divinylic ketones. Cyclizations are also observed after acylations of cyclohexenes with vinylacetyl chloride derivatives (equation The acylation-cycloalkylation sequence provides a complement for the Robinson annelation, since the carbonyl function is located adjacent to the bridgehead position. This potential has been realized in natural product syntheses. ... 

Aromatic, aliphatic and heterocyclic acid chlorides all give high yields of ketones, [1,4] addition not being observed with a,3-unsaturated acid chlorides. This leads to a potentially very useful synthesis of divinyl ketones since, in contrast to Lewis acid catalyzed acylations of alkenes, under the neutral reaction conditions for the acylation of alkenylstannanes, cyclizations to cyclopentenones do not occur. 

Aromatic or a,3-unsaturated acid chlorides were found to undergo rapid oxidative addition with these palladium complexes, and the subsequent acylation of an organotin prooeeded smoothly in HMPA (1-60 nun) or in acetone. Formation of simple aliphatic acylpalladium(II) complexes proceeds at markedly reduced rates and the acylation of organotins is slower but still use (10-24 h). 

With these conditions in hand, the development of a one-pot four-component synthesis of pyrrolopyridine was straightforward (Scheme 15.18). Thus, heating a toluene solution (60 °C) of an aldehyde, an amine, and an a-isocyanoacetamide (23) in the presence of ammonium chloride (1.5 equiv) for 4 h afforded the oxazole. After cooling the above reaction mixture to 0°C, an a,fi-unsaturated acyl chloride and triethylamine were introduced to it. Heating to reflux the resulting solution produced then pyrrolo[3,4-b]pyridin-5-one (52). In this one-pot four-component reaction, two C-N bonds and three C-C bonds were created with the formation of a bicyclic core. 

Enantioselective organocatalytic synthesis of 3,4-dihydro-2H-pyran-2-ones can be accomplished through a nucleophile-catalyzed Michael addition-proton transfer—enol lactonization of a,P-unsaturated acyl chlorides and 1,3-dicarbonyl compounds (Scheme 47) (13AGE13688). 

Aldehydes and ketones condense with ketene in the presence of 1 equiv of boron trichloride to give a,p-unsaturated acyl chlorides. Aryl isocyanates are converted into allophanyl chlorides, which are precursors for industrially important 1,3-diazetidinediones (eq 7). ... 

The acylpalladium complex formed from acyl halides undergoes intramolecular alkene insertion. 2,5-Hexadienoyl chloride (894) is converted into phenol in its attempted Rosenmund reduction[759]. The reaction is explained by the oxidative addition, intramolecular alkene insertion to generate 895, and / -elimination. Chloroformate will be a useful compound for the preparation of a, /3-unsaturated esters if its oxidative addition and alkene insertion are possible. An intramolecular version is known, namely homoallylic chloroformates are converted into a-methylene-7-butyrolactones in moderate yields[760]. As another example, the homoallylic chloroformamide 896 is converted into the q-methylene- -butyrolactams 897 and 898[761]. An intermolecular version of alkene insertion into acyl chlorides is known only with bridgehead acid chlorides. Adamantanecarbonyl chloride (899) reacts with acrylonitrile to give the unsaturated ketone 900[762],... 

Acylation of the enamine (113) with a,/9-unsaturated acid chlorides has been shown (57) to give bicyclo(3.3.1)nonan-2,9-diones. Acryloyl ehloride on reaction with the enamine (113) and subsequent hydrolysis gave bicyelo-(3.3.1)nonan-2,9-dione (123). Mechanistic studies suggest that C alkylation by the olefin precedes acylation (87). 

A strategy involving sequential 1,3-dipolar cycloadditions has been reported for the synthesis of novel bis-isoxazolo substituted piperidines 192a and 192b (Eqs. 18 and 19) [53]. It consists of the Michael addition of an unsaturated alkox-ide 185 to )3-nitrostyrene 184 followed by an INOC or ISOC reaction to provide isoxazolines 187-189 (Eq. 18 and Table 18). A polymer supported acyl chloride... 

Reactions of allylzinc halides with carbon nucleophiles are rare examples of uncatalyzed transformations of organo-zinc compounds. Allylzinc bromide, formed in situ, reacted with a number of structurally diverse acyl chlorides furnishing the corresponding ketones 222 in high yields (Scheme 129).330 No isomerization to the corresponding a,(3-unsaturated ketones was observed under the conditions used (RT, 5min-6h). 

The acyl anion chemistry of acylzirconocene chlorides has also been applied to the stereoselective preparation of ( )-a,(3-unsaturated selenoesters and telluroesters (Scheme 5.35) [38]. Although no carbon—carbon bond was formed, this reaction reflects the synthetic interest in ( )-a,(3-unsaturated selenoesters and telluroesters, which are well-known precursors of acyl radicals and acyl anions, respectively. 

While attempting to prepare an T71-(vinylcarbene)iron complex121 by the alkylation or acylation of an a,/3-unsaturated acylferrate, Mitsudo and Wa-tanabe found122 that the major isolated product was in fact an -vinylketene complex (178), formed presumably by the carbonylation of an intermediate V-vinylcarbene, which may then undergo olefin coordination to the vacant metal site. All attempts to isolate such intermediates, or to observe them by 13C NMR spectroscopy, failed. Only in the reaction between potassium tetracarbonyl -cinnamoy ferrate (179.a) and pivaloyl chloride (180.b) was a side product (181) isolated in appreciable yield. In other reactions, only a trace (<1%) of such a compound was detected by spectroscopy. The bis(triphenylphosphine)iminium(l + ) (PPN) salts of 179.a and 179.b also reacted with 2 equiv of ethyl fluorosulfonate to give 178.g and 178.h in 21 and 37% yield, respectively. All products were somewhat unstable to silica gel, hence the low isolated yields in some cases. 

In order to modulate the reactivity of intermediate 331, it was transformed into its copper derivative by treatment with copper(I) bromide or iodide in THF at —78 °C, and then was allowed to react with a,/3-unsaturated carbonyl compounds (to give compounds 343 resulting from a conjugated addition), acyl chlorides (to give ketones 344) and copper(II) chloride (to dimerize giving compounds 345) (Scheme 100)"° ". ... 

Zinc was effectively activated from zinc chloride using lithium and a catalytic amount (10%) of naphthalene in order to prepare secondary or tertiary alkylzinc bromides 517 (starting from the corresponding aUcyl bromides 516). These reagents react with acyl chlorides or a,/3-unsaturated ketones to give the expected ketones 15 and 518 (Scheme 143). 

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