Branched alkyl iodides

All alkyl halides used in the couplings were primary, although some of them were branched or had an ester functionality. Some of the dialkylzincs had a functional group without affecting the outcome of the reaction. For example, organozinc derivative 302 with a silyl enol ether group reacted with alkyl iodide 303, affording the desired product 304 in 65% yield (Scheme 153). 

Primary alkyl iodides and bromides are excellent substrates for the Victor Meyer reaction, providing a route to both substituted and unsubstituted nitroalkanes (Table i. i).63,65,70,7i formation of the corresponding nitrite ester is a side-reaction and so the nitroalkane is usually isolated by distillation when possible. The reaction of primary alkyl chlorides with silver nitrite is too slow to be synthetically useful. Secondary alkyl halides and substrates with branching on... 

As stated above, intermolecular coupling reactions between carbon atoms are of limited use. In the classical Wurtz reaction two identical primary alkyl iodide molecules are reduced by sodium. n-Hectane (C100H202), for example, has been made by this method in 60% yield (G. Stallberg, 1956). The unsymmetrical coupling of two alkyl halides can be achieved via dialkylcuprates. The first halide, which may have a branched carbon chain, is lithiated and allowed to react with copper(I) salts. The resulting dialkylcuprate can then be coupled with alkyl or aryl iodides or bromides. Although the reaction probably involves radicals it is quite stereoselective and leads to inversion of chiral halides. For example, lithium diphenyl-cuprate reacts with (R)-2-bromobutane with 90% stereoselectivity to form (S)-2-phenylbutane (G.M. Whitesides, 1969). 

The superior nucleophilicity and excellent thermal stability of pseudoephedrine amide enolates make possible alkylation reactions with substrates that are ordinarily unreactive with the corresponding ester and imide-derived enolates, such as (3-branched primary alkyl iodides. Also, alkylation reactions of pseudoephedrine amide enolates with chiral (J-branched primary alkyl iodides proceed with high diastereoselectivity for both the matched and mismatched cases (Table 3). ... 

Appropriate alkyl iodides or bromides were reacted with 57 and 2-epi-Sl in the presence of Ag20 in CH3CN with yields ranging from 36 to 77% (74, Scheme 10) [34, 51]. However, with these conditions preparation of branched alkyl ethers was unsuccessful [51]. Reacting 57 with chloromethyl methyl ether, diisopropylethy-lamine, and catalytic DMAP in CH2CI2 afforded 75 in a 72% yield and was the first 1 derivative reported to have increased affinity at the KOP receptor relative to 1. [41, 52]. Based on the successful increase in affinity of derivative 75, additional simple alkoxymethyl ethers were obtained using appropriate alkyoxymethyl chloride with diisopropylethylamine in DMF (76-78). However, more complex alkoxymethyl derivatives were synthesized from the common methylthiomethyl ether intermediate (79), which was obtained from reaction of 57 with acetic acid, acetic anhydride, and dimethylsulfoxide (DMSO) [52]. Compound 79 was then... 

With the exception of 4-(1,1,3,3-tetramethylbutyl)phenol prepared from diisobutylene, all the mutti-branched alkylphenols discussed consist of isomeric mixtures. In the pursuance of structure/property interests several studies have aimed to synthesise pure compounds. Thus by Wurtz-type methodology the reaction of the isomeric chloroanisoles with (i) alkyl iodides in ethereal solution in the presene of sodium and (ii) demethylation of the resultant alkylanisoles with aluminium bromide, a range of C5, Cg and Cg alkylanisoles has been synthesised (ref. 14). Numerous other methods are available for the synthesis of the isomeric n-, iso-, sec- and tert-alkylphenols some of which are referred to in Chapter 13. Reaction of a mixture of the appropriate alkyl chloride and 2-,... 

For aliphatic halogen compounds, the molecular ion peak is strongest with alkyl iodides, less strong for alkyl bromides, weaker for alkyl chlorides, and weakest for alkyl fluorides. Furthermore, as the alkyl group increases in size or as the amount of branching at the [a] position increases, the intensity of the molecular ion peak decreases. 

However, 1,2,3-benzotriazines bearing various benzyl groups <1981JCM324, 1981JRM3786> or various hydroxylated branched alkyl groups at C-4 could not be quaternized by propyl iodide in ethanol or 1-butanol at reflux temperature <1986EJM87>. 

When a branching point in the skeleton falls outside the reach of a functional group, one can rely on skeletal bond-forming reactions which do not require the presence of a functional group. A nearly ideal solution to this problem is provided by the transition metal-catalyzed coupling reactions of alkylzinc or alkylmagnesium reagents with alkyl iodides [2, 3,4,5] (Scheme 3.4). 

The free-radical addition of TFE to pentafluoroethyl iodide yields a mixture of perfluoroalkyl iodides with even-numbered fluorinated carbon chains. This is the process used to commercially manufacture the initial raw material for the fluorotelomer -based family of fluorinated substances (Fig. 3) [2, 17]. Telomeri-zation may also be used to make terminal iso- or methyl branched and/or odd number fluorinated carbon perfluoroalkyl iodides as well [2]. The process of TFE telomerization can be manipulated by controlling the process variables, reactant ratios, catalysts, etc. to obtain the desired mixture of perfluoroalkyl iodides, which can be further purified by distillation. While perfluoroalkyl iodides can be directly hydrolyzed to perfluoroalkyl carboxylate salts [29, 30], the addition of ethylene gives a more versatile synthesis intermediate, fluorotelomer iodides. These primary alkyl iodides can be transformed to alcohols, sulfonyl chlorides, olefins, thiols, (meth)acrylates, and from these into many types of fluorinated surfactants [3] (Fig. 3). The fluorotelomer-based fluorinated surfactants range includes noiuonics, anionics, cationics, amphoterics, and polymeric amphophiles. 

Normant and his co-workers have described a new simple two-step procedure for the conversion of alkyl halides into the corresponding chain-elongated acetylene in good yield. The procedure involves reaction of the halide with dichloromethyl-lithium in the presence of one equivalent of HMPA. If the group R is branched, the alkyl iodide is preferred over the bromide. Treatment of the... 

The starting phosphonium salts are themselves readily obtained by reaction of triaryl- or trialkylphosphines vith an alkyl halide (Scheme 1.4). In general, primary alkyl iodides and benzyl bromides are converted to the corresponding phospho-nium salts by heating with triphenylphosphine at 50 °C in THF or CHCI3, while primary alkyl bromides, chlorides, and branched halides usually require more vigorous conditions (for example, heating to 150 °C). These reactions can be carried out neat, or in acetic acid, ethyl acetate, acetonitrile or DMF solution. 

The reaction with p-branched primary alkyl iodides provides an iterative method to prepare deoxypropionates. The alkylations are then performed at room temperature and afford high yields (>90%) and excellent diastereoselec-tivities even when the psendoephedrine carboxamide reacts with chiral p-branched primary alkyl iodides in a mismatched fashion (dr= 142 1-1 199) (Table 2.3). 

TABLE 2.3 Myers Alkylation with P-Branched Primary Alkyl Iodides... 

In the case of AE, HI or HBr fission produces the alkyl iodides or bromides derived from the starting alcohols, as well as the decomposition products from the ethoxy chain described above. The alkyl halides can be readily characterized as to chain length and isomer distribution by gas chromatography (72). An eight-laboratory collaborative study of AE characterization by HI cleavage-GC gave coefficients of variation between laboratories of 1-2% for determination of the major components of a linear alcohol initiator and about twice that for branched alcohols (77). The ethyl and propyl compounds from decomposition of the alkoxy chain may be quantified if the E/P ratio or degree of ethoxyla-tion is to be determined, but such information is more easily available from NMR analysis. 

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