Bromomethylation, arenes

Based on their interest in medium-size ring synthesis, Takahashi and co-workers used a copper(l) salt to mediate the [4+ 4]-reaction of zirconacyclopentadienes 82a, 82b and 82d and l,2-bis(bromomethyl)arenes (Scheme 31).85 The reaction works with substoichiometric amounts of copper(l) chloride (10 mol%), but in general higher yields and faster reaction times are observed with 2 equiv. 

As an extension of their work on the [4+ 4]-reaction of zirconacyclopentadienes and l,2-bis(bromomethyl)arenes (Section 10.13.2.4), Takahashi and co-workers reported a [5 + 4]-reaction based on the use of l,8-bis(bromomethyl)-naphthalene as the five-carbon component.85 As with the [4 + 4]-reaction, the [5 +4]-reaction works with a catalytic amount of CuCl, but higher yields and faster reactions result when stoichiometric CuCl and 1,3-dimethyl-3,4,5,6-tetrahydro-2(l//)-pyrimidinone(iV,iV -dimethylpropyleneurea) (DMPLJ) are used (Scheme 42). 

The vinyl triflate of Komfeld s ketone has been subjected to Heck reactions with methyl acrylate, methyl methacrylate, and methyl 3-(Af-rerf-butoxycarbonyl-lV-methyl)amino-2-methylenepropionate leading to a formal synthesis of lysergic acid [259]. A similar Heck reaction between l-(phenylsulfonyl)indol-5-yl triflate and dehydroalanine methyl ester was described by this research group [260]. Chloropyrazines undergo Heck couplings with both indole and 1-tosylindole, and these reactions are discussed in the pyrazine Chapter [261], Rajeswaran and Srinivasan described an interesting arylation of bromomethyl indole 229 with arenes [262]. Subsequent desulfurization and hydrolysis furnishes 2-arylmethylindoles 230. Bis-indole 231 was also prepared in this study. 

Bromomethylation of arenes using 1,3,5-trioxane and hydrobromic acid is catalysed by the addition of a phase-transfer catalyst. Yields in excess of 90% are attained using (tetradecyl)trimethylammonium bromide under relatively mild conditions for a range of arenes [55]. Tetra-n-butylammonium bromide is ineffective, suggesting the catalytic effect may be micellar. 

Dihydrobenzo[c]tellurophene and 2,5-dihydronaphtho[2,3-r]tellurophene, obtained from the l,2-[bromomethyl]arenes and sodium tclluride, when heated at 500° in an atmosphere of helium extruded tellurium and formed cyclobutenes in good yields2. 

Synthesis of calixspherand diols from p-f-butylcalix[4]arene and 3,3"-bis(bromomethyl)-1,1 3, 1"-terphenyls9 (Scheme 8.6)... 

Alkylation of r-butylcalix[8]arene with l,2-bis-(bromomethyl)benzene led to the doubly bridged derivative 87 in 19% yield.167 In contrast to 86 it is achiral ( >M... 

The series of arene-containing polyazamacrocycles was prepared by reaction between diethoxyphosphoryl (Dep)-protected l,3-bis(aminomethyl)benzene and l,3-bis(bromomethyl)benzene, giving cyclic products 28-30 (Equation 4) <2005S2845>. Analogous tetraaza and hexaaza macrocycles were formed by reaction of l,4-bis(bromo-methyl)benzene with the protected amine in 11% and 14% yields, respectively <2005S2845>. 

Similar reaction of tris(SES) triamines (diethylenetriamine and dipropylenetriamine) with a series of bis(bromo-methyl)arenes (naphthalene, anthracene) afforded arene-containing macrocycles in high yields <2001JOC2722>. Alternatively, o-nitrobenzenesulfonyl (nosyl, Ns) <2001BML1521> or nosyl/trifluoroacetyl <20010L3499> derivatives of ethylene-propylenetriamine and dipropylenetriamine were cyclized with methyl 3,5-bis(bromomethyl)benzoate... 

Although the situation is even more complicated with calix[8]arenes, crown ether derivatives with 1,2- 1,3-, 1,4- and 1,5- bridging have been obtained in good to excellent yields (88% and 78% for l,5-crown-2 and l,5-crown-3) ° . 1,5-Bridged derivatives have been obtained with o- and / -bis(bromomethyl)benzene °, and 1,4-bridged derivatives... 

Bromomethylation of arenes. The introduction of up to three bromomethyl groups is achievable through varying the stoichiometry of paraformaldehyde and the reaction conditions. 

The reactions between Y-(co-haloalkyl)phthalimides and sodium dialkyl phosphite were reported as early as 1949 by Chavane in the successful sytheses of several (co-aminoalkyl)phosphonic diesters. The advantage over the Michaelis-Arbuzov reaction in the preparation of (2-aminoethyl)phosphonic diesters with Y-alkyl or Y-silvl substituents is worth recalling, and several reports of its successful use may be noted, including the preparation of nitrogen-functionalized polyphosphonic esters (Scheme 17). Other substrates for the reaction have included l,3-bis(bromomethyl)benzene and 4-(co-bromoalkyl)arenes ... 

Tetrameric caHx[2]benzimidazolone[2]arenes 178a and 178b and octameric calix[4]benzimidazolone[4] arenes 179a-f, have been formed by high dilution and template induced condensation of l,3- > (bromomethyl)benzene and the trinuclear... 

For achieving deep cavities in higher level supramolecular structures, lower rim conjugates 51-53 of calix[6]arene and pyridine having larger sized linkers have been obtained by 3-fold reactions of 2-[4-(bromomethyl)phenyl]pyridine, 5-(bromomethyl)-2-phenylpyridine and 5-(bromomethyl)-2-[9,9-di-M-hexylfluorenyl]pyridine with 1,3,5-trimethyl ether of the p-bu -calix[6]arene in the presence of NaH. These conjugates elaborated mainly cone conformations (2006JCXH9589). 

The calix[6]arene 65 bridged by a 1,10-phenanthroline was synthesized from p-bu -calix[6]arene and 2,9-bis(bromomethyl)-l,10-phenan-throline (97TL4539). Its complex with Cu has been beneficially used for Cu catalyzed cyclopropanation of styrene and indene. Several chiral derivatives of 65 have been synthesized but the stereoselectivity of cyclopropanation, catalyzed with their Cu complexes, could not be enhanced (2006EJ04717). A similar bridging of calix[5]arene and calix[8]arene has also been investigated (2005EJ02330). 

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