Acid chlorides vinyl substitutions

Formation of a vinyl-substituted pyrrolizidine derivative is also observed in case of an allylstan-nane cyclization94. Since the allylstannane moiety is acid sensitive, the iV-acyliminium ion is generated by exposure of the hydroxylactam to methanesulfonyl chloride and triethylamine in dichloromethane. The very rapid cyclization produces the endo-vinyl compound with very high stereoselectivity. 

For example, a proline-based chiral ligand was attached to a vinyl-substituted monomer (Fig. 42.15) by reacting vinylbenzoyl chloride with the amine functionality of the ligand [106]. As mentioned previously, the apolar Merrifield resin as a support is not swollen in polar solvents. Hence, in order to match the polarity of the resin with that of the typically used substrates in enantioselective hydrogenation, the functionalized monomer was copolymerized with polar units of methacrylic acid 2-hydroxyethyl ester. 

Scheme 3.42. Substitution reactions between a-aminoalkyl-cuprates and acid chlorides [166], vinyl triflates [167], and vinyl iodides (Boc = t-butoxycarbonyl) [168].

The procedure described here offers a general route to a variety of unsymmetrically substituted y-pyrones from Meldrum s acid.2 Substitution at the 2-position depends on the acid chloride chosen, while substitution at the 5-position is derived from the vinyl ether. A variety of substituted y-pyrones have been synthesized by utilization of this method as illustrated in the Table. The intermediate pyrandione is believed to arise through the addition of the vinyl ether to an acyl ketene that results... 

VINYL SUBSTITUTION WITH ORGANIC HALIDES, DIAZONIUM SALTS, ACID CHLORIDES, 842... 

Vinyl Substitutions with Carboxylic Acid Halides, Aryl Sulflnates and Arylsulfonyl Chlorides 856... 

Normally, the most practical vinyl substitutions are achieved by use of the oxidative additions of organic bromides, iodides, diazonium salts or triflates to palladium(0)-phosphine complexes in situ. The organic halide, diazonium salt or triflate, an alkene, a base to neutralize the acid formed and a catalytic amount of a palladium(II) salt, usually in conjunction with a triarylphosphine, are the usual reactants at about 25-100 C. This method is useful for reactions of aryl, heterocyclic and vinyl derviatives. Acid chlorides also react, usually yielding decarbonylated products, although there are a few exceptions. Likewise, arylsulfonyl chlorides lose sulfur dioxide and form arylated alkenes. Aryl chlorides have been reacted successfully in a few instances but only with the most reactive alkenes and usually under more vigorous conditions. Benzyl iodide, bromide and chloride will benzylate alkenes but other alkyl halides generally do not alkylate alkenes by this procedure. 

The same reactions, carried out with potassium carbonate as base in place of a secondary amine, yield exocyclic dienes in good yield, although double-bond isomerization sometimes occurs (equation 38).93 Inclusion of tetra-zi-butylammonium chloride in the reaction mixture stops the double-bond isomerization. Thus, the reaction in equation (38) with the chloride yields only the bis(exomethylene) product in 45% yield in a slow reaction. Some N- and O-heterocyclic products, also, have been prepared by the intramolecular vinyl substitution reaction.94 A 16-membered ring lactone was made by the ring closure of a vinylic iodide group with a vinyl ketone group. The yield, based upon the reactant, was 55% but a stoichiometric amount of bis(acetonitrile)palladium dichloride was employed. The catalyst was prereduced with formic acid so that the reaction proceeded at 25 C (equation 39).95... 

Highly substituted amides (29) have been prepared in a three-component reaction of an imine, an acid chloride, and trialkylindium.79 Proceeding under mild conditions and high metal efficiency, the alkyl group on indium can also be aryl, heteroaryl, or vinyl. 

Vinylic substitutions in otherwise unreactive systems can take place easily in the presence of metal salts. The chlorine atom of vinyl chloride is replaced by acetic acid, isopropyl alcohol and n-butylamine in the presence of catalytic amounts of PdCl2 in iso-octane (Stern et al., 1966). 

Like other acid chlorides and cyanogen bromide, vinyl chloroformate brings about fission of benzylic and allylic amines e.g. hydrastine is converted into the enol lactone (145).169 Normorphine and norcodeine give substituted thioureas (146) with alkyl isothiocyanates.170... 

The chemistry of iron vinylidene complexes is dominated by the electrophilicity of the carbon atom adjacent to the iron organometallic unit. While addition of water leads to an acyl complex (i.e., the reverse of the dehydration shown in equation 10), addition of an alcohol leads to a vinyl ether complex. Similarly, other iron vinyl complexes can be prepared by the addition of thiolate, hydride, or an organocuprate (Scheme 33). " The nucleophilic addition of imines gave enaminoiron intermediates that could be further elaborated into cyclic aminocarbenes. This methodology has been used to provide access to /3-lactams and ultimately penicillin analogs, and good diastereoselectivities were observed (6 1-15 1) (Scheme 34). 04 Iso, vinylidene complexes are intermediates in cyclizations of alkynyl irons with substituted ketenes, acid chlorides, and related electrophiles an example is shown (equation 11). These cyclizations led to the formation of a series of isolable and characterizable cyclic vinyl iron complexes. 

Numerous aryl bromides, iodides [203], borates [204] and triflates [205, 206] have been successfully carbonylated. Triflates could serve as a route for the synthesis of arenecarboxylic acid derivatives from phenols. This carbonylation using dppf in a catalytic mixture generally shows higher efficiency than PPhj or P(o-Tol)3 [207]. Poor performance is also noted for PPhj in a Pd-catalyzed vinyl substitution of aryl bromides [208]. Side-reactions involving the formation of [PPhjAr]Br and ArH are responsible. A system which is catalyzed effectively by PdCljfdppf) under 10 atm CO is the desulfonylation of 1-naphthalenesulfonyl chloride 58 in the presence of Ti(OiPr)4. Formation of isopropyl 1-naphthoate 59 can be explained in a sequence of oxidative addition, SOj extrusion, carbonylation and reductive elimination (Fig. 1-27) [209]. A notable side-product is di-l-naphthyl disulfide. 

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). ... 

The application of the aliphatic Friedel-Crafts reaction (chapter 5) to alkynes is a stereoselective approach to vinyl-lithiums that forms a bridge between the Shapiro reaction and the next section-hydrometallation. Acid chlorides 64 react with alkynes under Lewis acid catalysis to give E-P-chloroenones -65 stereoselectively. The chlorine can be replaced by more reactive iodine by conjugate substitution.11... 

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