Alkylation with 2,5-dibromo-2-methyl

Geminal substituted dibromoalkenes can be prepared by the alkylation of dibromomethyllithium with a-chloroalkyl methyl ethers. Deprotonation of the alkylation products results in the elimination of methanol and the formation of the corresponding 1,1-dibromoalkenes. Despite the lower acidity of 1 -bromo-1 -chloroalkyllithiums relative to the dibromo analogs they exhibit similar nucleophilic proper-ties. Alkyl dichloroacetates can also be deprotonated with lithium diethylamide and alkylated with a range of alkyl halides. ... 

Methylation reactions (N versus S) of 2-thiophenobarbital under various conditions have been performed [94MI(68)117]. There is also a report on the ratio of N- and 6>-alkylation of 4(3/7)-quinazolinones depending on the nature of a substituent in position 2 [93CPB(41)1114].. Quinazoline-2,4(l//,3W)-d ones have been alkylated with l,4-dibromo-2-methylbut-2-ene under phase-transfer conditions to give dialkylated as well as monoalkylated products [93JHC(30)lil71. 

Dibromo-compound (50) may be deprotonated with LDA and either alkylated with for example methyl iodide to give compound (51), as shown in eq 32, or treated with different chlorosi-lanes to yield the unsymmetrically substituted dibromodisilyl-methane (52) that may be further converted to the 1,1-disilylethene (53) upon monomethylation with lithium trimethylmagnesate and base-promoted dehydrobromination (eq 33). ... 

Early investigators adduced various kinds of chemical evidence in support of a monohydroxy-dioxo structure for barbituric acid (112) (a) reaction with diazomethane afforded a mono-O-methyl deriva- iye,i59,i6o barbituric acid and its 5-alkyl derivatives are much stronger acids than the 5,5-dialkyl derivatives, and (c) the 5-bromo and 5,5-dibromo derivatives have different chemical properties. - The early physical evidence also appeared to substantiate the monoenol structure, this formulation having been suggested for barbituric acid in 1926 on the basis of its ultraviolet spectrum and again in 1934, In the 1940 s, ultraviolet spectroscopic studies led to the suggestion of other monohydroxy and dihydroxy structures for barbituric acid, whereas its monoanion was assigned structure 113 (a clear distinction between ionization and tautomerism was not made in these papers). 

Various alkyl- and aryl-substituted [3]radialenes could be prepared from 1,1-dihaloal-kenes using organometallic pathways. Hexamethyl-[3]radialene (25), the first [3]radialene to be synthesized, was obtained in a very low yield by treatment of l,l-dibromo-2-methyl-1-propene (22) with butyllithium8,9. The lithium carbenoid 23 and the butatriene 24 are likely intermediates of this transformation (Scheme 2), the former being the source of an unsaturated carbene moiety which is transferred onto the latter. However, the outer double bonds of 24 are more readily cyclopropanated than the central one. 

In this method, Furstner converts N-BOC protected pyrrole to the 2,5-dibromo compound (122) with NBS and this is followed by metalation and carbomethoxylation with t-butyl lithium in THF and subsequent trapping of the metalated species with methyl chloroformate to yield a pyrrole diester (123). Bromination of this diester at positions 3 and 4 with bromine in water followed by Suzuki cross-coupling with 3,4,5-trimethoxyphenyl boronic acid yields the symmetrical tetrasubstituted pyrrole (125). Base-mediated N-alkylation of this pyrrole with 4-methoxyphenethyl bromide produces the key Boger diester (126) and thereby constitutes a relay synthesis of permethyl storniamide A (120). 

Methyl iodide (31) reacts with silver nitroform (32) in acetonitrile to give a 51 % yield of 1,1,1-trinitroethane (33). ° The potassium salt of nitroform in acetone has been used for the same reaction.Yields between 28 % and 65 % have been reported for the reaction of silver nitroform in acetonitrile with higher molecular weight alkyl iodides. The choice of solvent is important in some reactions, for example, silver nitroform reacts with l,4-dibromo-2-butyne (34) in solvents like dioxane and acetone to give l,l,l,6,6,6-hexanitro-3-hexyne (35) in approximately 72 % yield, whereas the same reaction in acetonitrile is reported to give a mixture of compounds. 

Boron trifluoride and boron trifluoride-diethyl ether complex can be used as a source of fluoride ions in the presence of hypobromites and hypochlorites, e.g. methyl hypobromitc, tert-butyl hypobromite, methyl hypochlorite in carbon tetrachloride at 25 C. The addition of bromine monofluoride" and chlorine monofluoride" to various alkenes is accompanied by the formation of the corresponding alkoxybromides and alkoxychlorides which hinder the isolation of the halofluorinated products.57 jV-Bromo- and A -chloro-substiluted alkyl- and arylamines. -amides, and -imides, A -chloro-A,-methylamine, A -bromo-A -methylamine, A -chloro-A, /V-dimethylamine, A-bromo-A.A-dimethylamine, ACV-dichloro-A -methylamine, V,fV-dibromo-,V-mcthylaminc, A -bromosuccinimide, -V-chlorosuccinimide, Af-bromoacct-amide, A.A -dichlorourethane, can be used in the reaction instead of the hypohalites. The reactions with various alkenes conducted in dichloromethane at room temperature in the presence of boron trifluoride-diethyl ether complex produce bromofluoro and chlorofluoro addition products in 40-80 % yield. However, the reactions are complicated by the addition of A -halo-succinimides and Af.A-dichlorourcthane to the C = C bonds.58... 

The Niki reaction474 (alkylation of dimedone by l,4-dibromo-2-methyl-2-butene, with formation of compound 218), applied to phloro-acetophenone and to 3-isopentyl-2,4,6-trihydroxyisobutyrophenone, leads respectively to 2,3-dihydrobenzofurans 219a and 219b. Furan 219b with toluene- >-sulfonic acid rearranges to the benzofuran 220b.475... 

In an application of the Niki reaction,474 the alkylation of 1,3-cyclohexanedione with trans-1,4-dibromo-2-methyl-2-butene (a reaction previously mentioned in connection with compound 218 (Section IV,A,3,c,iv) leads to a similar product, without methyl groups in position 6.721... 

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