Chloromethyl olefination

Figure 34 A polymer-supported metallocene catalyst (51) with a weakly coordinating anion, [B(C6F5)4] , produced from lightly cross-linked, chloromethylated polystyrene beads for olefin polymerization. (Adapted from ref. 75.)...

The next four procedures describe the preparation of strained ring systems. Preparation of 3-CHLORO-2-(CHLOROMETHYL)-l-PROPENE provides a facile approach to the olefin required for the synthesis of [1.1.1 [PROPELLANE, one of the most strained hydrocarbons prepared to date. The ready availability of this hydrocarbon should prove particularly useful to those interested in the development of the chemistry of this fascinating compound. Preparation of N-BENZYL-2,3-AZETIDINEDIONE provides an efficient approach to the unadorned a-keto-/3-lactam, a potential... 

The reaction of chloromethyl aryl ethers with nucleophilic reagents has been described by Barber et al Thus, by reaction with thiourea, potassium thiocyanate, or sodium cyanide, there arc obtained aryloxyalkylisothiouronium salts, aryloxyalkyl thiocyanates, and aryloxyalkylacetonitriles, respectively. The reaction of chloromethyl aryl ethers with butyllithium leads to an aryloxycarbene which on reaction with olefins gives aryloxy-cyclopropanes. The ethers react with triphenylphosphine and a base to give phcnoxymethylene ylides which arc useful in con-... 

Metal-Halogen Compounds. An unusual example of the addition of a metal halide to a conjugated diene has been reported. The complex formed from palladium chloride and butadiene has been shown to be a dimer of 1-chloromethyl-7r-allylpalladium chloride, (85). Whether this is a true insertion reaction or some type of ionic reaction has not been determined, but its close analogy with the olefin-palladium chloride insertion reaction mentioned above would suggest an insertion mechanism for the diene reaction also. 

Carbamate esters also produced 2-oxo compounds, e.g., the esters of 3-aminopropanol88 and of 3-halogenopropanol.87 A few compounds have thus been prepared from carbamates, e.g., 20, with an aromatic substituent88 [Eq. (10)] or a heterocyclic one.89 Ethyl 7V-(3-hydroxy-propyl) urethanes cyclize to 2-oxo compounds with sodium methoxide.78 An interesting novel approach was to react an A-(chloromethyl)-carbamate with olefins to yield 2190 [Eq. (11)]. 

For 43, a new olefination reaction was discovered. 2-[4-(chloromethyl)phe-nyl]benzoxazole is treated in polar aprotic solvents with strong bases [76],... 

S l substitution of different compounds by nitronate anions followed by elimination of nitrous acid is a good method for the synthesis of various substituted olefins. A clear example is the base-promoted HN02 elimination from the C-alkylation products formed by the S l reaction between 2-chloromethyl-3-nitroimidazo[l,2-a]pyridine (11) and various aliphatic, cyclic and heterocyclic nitronate anions87, affording new potential pharmacological derivatives with a trisubstituted double bond at the 2-position. A representative example is shown in equation 32. 

A similar procedure can be applied to the synthesis of a series of 5-nitroimidazoles83 with antibacterial properties.The S l reaction of various l-alkyl-2-chloromethyl-5-nitroimidazoles (23) with heterocyclic nitronate anions prepared from 3-nitrolactams, under phase transfer catalysis, afforded trisubstituted olefins (equation 33). 

The formation of norcaradiene derivatives with naphthalene [reaction (22)] lends some support to this scheme. This mechanism resembles a bimolecular two-step process suggested for the reaction of chloromethyl-aluminum compounds with olefins (199-201). On the other hand, a bimolecular one-step methylene transfer mechanism is generally accepted for the formation of cyclopropane derivatives by the reaction of halo-methylzinc compounds with olefins. This difference between the mechanism proposed for the cyclopropane formation from olefin and that for the ring expansion of aromatic compound may be ascribable to the difference in the stability of intermediates the benzenium ion (XXII) may be more stable than an alkylcarbonium ion (369). 

The addition of a chloromethyl ether to olefinic linkages takes place under conditions similar to the Friedel-Crafts reaction and leads to y-chloro ethers. Substitution of zinc chloride for mercuric chloride as catalyst has improved the yields. Allyl chloride and chloromethyl ether react to give a high yield of l-methoxy-3,4-dichlorobutane (98%). ... 

Reactive halogen compounds such as benzyl chloride, 2-thenyl chloride, 2-bromoacetylthiophene, (C HjS)COCH,Br , and 2-chloromethyl-thianaphthene (C,H5S)CHjCl are readily converted to esters by treatment with the sodium salts of carboxylic acids. A small amount of tri-ethylamine has proved to be an effective catalyst. Acetates are oftentimes made by heating halides with fused sodium acetate in glacial acetic acid, e.g., p-ethylbenzyl acetate (93%). The reaction is of little value for the preparation of simple aliphatic esters. Secondary and tertiary halides give increasing amounts of olefin by dehydro-halogenation. 

Preparation of (R)-l involves the chlorination of (R)-l,l-bina-phthyl-2,2-dicarboxylic acid with scc-BuLi and hexachloro-ethane. Condensation of the resulting dichorinated product with 3-chloro-2-chloromethyl-l-propene, followed by oxidative cleavage of the olefin moiety with ruthenium trichlorde affords (R)-l in modest yields. 

Both benzyltriethylammonium chloride (1) and benzyltriethylammonium hydroxide (2) partition between the aqueous and organic phases. In the aqueous phase, the quaternary ammonium chloride (1) reacts with concentrated hydroxide to give the quaternary ammonium hydroxide (2). In the chloroform phase, 2 reacts with chloroform to give the tri-chloromethyl anion (3), which eliminates chloride ion to give dichlorocarbene, iCClj, (4), and 1. The carbene (4) reacts with the olefin to give product (5). 

Significantly increased ee values were obtained by using the new chiral PTCs 31 and 32, which can be easily prepared starting from 2-hydroxy-3-chloromethyl-5-methyl benzaldehyde and cinchonine or cinchonidine, respectively [30]. By using 31 or 32, up to 95% ee was achieved in the reaction of electron-deficient olefins with N-acyl-N-arylhydroxylamines as nitrogen transfer reagents under biphasic conditions (toluene/aqueous NaOH) at room temperature (Scheme 5.24). 

Olefin additions Bromine azide. Bromine chloride. Bromine (chlorine) dipyridine nitrate. N-Bromoacetamine. N-Bromoacetamide-DMSO-Water. N-Bromoacetamide-Hydrogen fluoride. n-Butyllithium. Dichloroketene. Dichloromethyl 2-chloromethyl ether. N,N-Dichlorourethane. Dichlorovinylene carbonate. Difluoramine. Ethyl azidoformate. Ethyl bromoacetate. Iodine azide. Iodine isocyanate. Iodine nitrate, lodobenzene dichloride. 1-lodoheptafluoropropane. Mercuric acetate. Nitrosyl chloride. Nitrosyl fluoride. Nitryl iodide. Rhodium trichloride. Silver fluoride. 

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