Allyl bromide iodide

Allyl halides are also alkylated by zinc cyanocuprates. Allylic bromides, iodides and chlorides react successfully with these reagents, and a number of functional groups in the allylic halide (ester, sulfide, sulfoxide, ether, alkyl halides, acetals) stand up well to the conditions of reaction (equations 29 and 30)41 3. The regiochemistry of attack is predominantly Sn2. 1,3-Dichloroalkenes can be made to undergo two successive coupling reactions to this point, only two identical R group incorporations have been reported (equation 31)44. 

Nickel-allyl complexes prepared from Ni(CO)4 and allyl bromides are useful for the ole-fination of alkyl bromides and iodides (E.J. Corey, 1967 B A.P. Kozikowski, 1976). The reaction has also been extended to the synthesis of macrocycles (E.J. Corey, 1967 C, 1972A). 

Indol-2-ylcopper reagents can also be prepared from 2-lithioindoles and they have some potential for the preparation of 2-substituted indoles. 1-Methyl-indol-2-ylcopper can be prepared by reaction of 2-lithio-l-methylindole with CuBr[10]. It reacts with aryl iodides to give 2-aryl-1-methylindoles. Mixed cyanocuprate reagents can be prepared using CuCN[ll], The cyan-ocuprate from 1-methylindole reacts with allyl bromide to give 2-allyl-l-methylindole. 

Similar methodology has been used to prepare the dialkoxyphosphinyldi-fluoromethylcopper compound 242 (equation 160) Functionalization with allyl bromide, methyl iodide, and iodobenzene occurs readily, as well as stereospecific syn addibon to hexafluoro-2-butyne [243. ... 

Few other reactions of series of substituted pyridines have been investigated extensively. Dondoni, Modena, and Todesco have measured the rate of N-oxidation of a limited series of pyridines and found a good correlation with normal u-values with a p-value of — 2.23. The A-alkylation of pyridines with alkyl iodides in nitrobenzene has been studied by Brown and Cahn and by Clarke and Rothwell. Unfortunately, the only data available are for the parent compound and for alkyl derivatives, and, since the a-values for the various alkyl groups in a given position are substantially constant, this leaves a correlation of only three independent points. However, the rates of A-alkylation of the j8- and y-alkyl derivatives are so nearly equal that it appears as if no correlation existed. Clarke and Rothwell have also studied the alkylation with allyl bromide in nitromethane at various temperatures, and in this case a more extensive series is available. The authors state that no overall Hammett correlation is obtained however, the j8-substituted derivatives fall on one straight line and the y-derivatives on another one with a different slope. The data are shown in Fig. 2. The line for the j8-compounds, p = — 2.53 0.31, r = 0.95, is seen not to be very good the line for the y-derivatives, p = — 1.42 0.06, r = 0.99, is much more satisfactory. It does not seem likely that the discrepancy is due to the intervention of resonance effects, since in this case one would expect the correlation for the y-derivatives to be poorer than that for the j8-analogs. More extensive studies with a wider variety of substituents would seem very desirable. 

We first tried to prepare 1-hydroxyyohimbine (23) and its derivatives. With 23 in hand (as described in Section II.D), its methylation with CH2N2 is carried out to provide 1-methoxy derivative 304 (77%) (Scheme 47). Utilizing K2CO3 as a base in DMF, allyl bromide, butyl iodide, and p-nitrobenzyl bromide react successfully with 23, resulting in the formation of 305 (93%), 306 (99%), and 307 (90%), respectively. All of these compounds, including 23 itself, are found to exhibit potent Q 2-blocking activity (2001H1237), and the details will be reported in due course. 

Allylation of the 7-hydroxyquinoline derivative 242 with allyl bromide gave the corresponding 7-allyl ether 243 which underwent Claisen rearrangement to give the 8-allyl derivative 244. Acylation and subsequent bromination afforded the dibromopropyl derivative 245. Treatment of 245 with KOH/EtOH gave 8-hydroxypyrroloquinoline 246 that was methylated with methyl iodide to afford 247 (91JOC980) (Scheme 44). 

In the preparation of the thiazides containing more highly functionalized side chains (183-185), an acetal of the aldehyde is usually used rather than the free carbonyl compound. Thus, trichlomethiazide (183) is prepared by reaction of 160 with the dimethyl acetal from dichloroacetaldehyde. In a similar vein, alkylation of the acetalthiol, 190, with allyl bromide affords 191. This yields altizide (184) on condensation with 160. Alkylation of 190 with 2,2,2-trifluoroethyl iodide gives 192. This leads to epithiazide (185) on condensation with 160. 

Alkylation reactions are subject to the same constraints that affect all Sn2 reactions (Section 11.3). Thus, the leaving group X in the alkylating agent R—X can be chloride, bromide, iodide, or tosylate. The alkyl group R should be primary or methyl, and preferably should be allylic or benzylic. Secondary halides react poorly, and tertiary halides don t react at all because a competing E2 elimination of HX occurs instead. Vinylic and aryl halides are also unreactive because backside approach is sterically prevented. 

Allyl cyanide has been found in oil of mustard 1 and has been prepared from allyl chloride and potassium cyanide,2 allyl bromide and potassium cyanide,3 allyl iodide and potassium cyanide4 and silver cyanide.5 The method described in the procedure is essentially that of Bruylants, who has shown that the yields are much better when dry cuprous cyanide is treated with allyl bromide.6... 

Both sides of acetone have been alkylated with different alkyl groups, in one operation, by treatment of the Al,lV-dimethylhydrazone of acetone with n-BuLi, followed by a primary alkyl, benzylic, or allylic bromide or iodide then another mole of n-BuLi, a second halide, and finally hydrolysis of the hydrazone. ... 

E = I2, H2O, allylic bromide, ethyl propiolate, aryl iodide... 

The first synthesis, by method a, of amylostatin (XG) was reported by Kuzuhara and Sakairi. The synthon for the cyclohexene moiety was the benzylated allyl bromide 382, derived from D-glucose by the sequence 378 — 382 of the Perrier reaction. The coupling reaction of 382 using an excess of 4-amino-T,6 -anhydro-4,6-dideoxymaltose tetrabenzyl ether (383), and sodium iodide in DMF for 3 days produced a mixture of the epimeric monocarba-trisaccharide derivatives, separation of which gave the protected derivatives in 15% yield. 

Secondary benzylic bromides, allylic bromides, and a-chloro ethers can undergo analogous reactions using ZnBr2 as the catalyst.1 2 Primary iodides react with silyl... 

A modification of this method, related to the Beckmann rearrangement, entails treatment of a ketoxime with one equivalent of CDI, then four to five equivalents of a reactive halide such as allyl bromide or methyl iodide (R3X) under reflux in acetonitrile for 0.5-1.5 h. Quatemization of the imidazole ring effectively promotes the reaction by increasing the electron-withdrawing effect. The target amides then are obtained by hydrolysis. High yields, neutral conditions, and a very simple procedure make this modification of the synthesis of amides by azolides a very useful alternative. 1243... 

Alone, or Air, or Hydrogen, or Carbon monoxide or Allyl bromide, or Trifluoromethyl iodide... 

Catalysts can also be immobilized through nonphosphine ligands. A new type of immobilized Pd° complex with a macrocyclic triolefin ligand (L30) has been successfully used for simple crosscoupling reactions of aryl iodides and allyl bromide with arylboronic acids, in both aqueous and anhydrous media.498... 

R3X = Aryl iodide, methyl 3-iodopropenoate, substituted allyl bromide... 

Functionalized organozinc halides are best prepared by direct insertion of zinc dust into alkyl iodides. The insertion reaction is usually performed by addition of a concentrated solution (approx. 3 M) of the alkyl iodide in THF to a suspension of zinc dust activated with a few mol% of 1,2-dibromoethane and MeaSiCl [7]. Primary alkyl iodides react at 40 °C under these conditions, whereas secondary alkyl iodides undergo the zinc insertion process even at room temperature, while allylic bromides and benzylic bromides react under still milder conditions (0 °C to 10 °C). The amount of Wurtz homocoupling products is usually limited, but increases with increased electron density in benzylic or allylic moieties [45]. A range of poly-functional organozinc compounds, such as 69-72, can be prepared under these conditions (Scheme 2.23) [41]. 

A more traveled route to the absolute configuration represented by cyclohexa-1,4-diene 8 involves Birch reduction-alkylation of benzoxazepinone 9.2.5 heterocycle is best prepared by the base-induced cyclization of the amide obtained from 2-fiuorobenzoyl chloride and (5)-pyrrolidine-2-metha-nol. o The molecular shape of enolate 10 is such that the hydrogen at the stereogenic center provides some shielding of the a-face of the enolate double bond. Thus, alkylation occurs primarily at the 3-face of 10 to give 11 as the major diastereomer. The diastereoselectivity for alkylation with methyl iodide is only 85 15, but with more sterically demanding alkyl halides such as ethyl iodide, allyl bromide, 4-bromobut-1-ene etc., diastereoselectivities are greater than 98 2. 

Reduction of allyl bromides and iodides at vitreous carbon in an aptotic solvent generally gives good yields of the dimer. This product arises by rapid substitution by the allyl carbanion, formed in an overall two-electron reaction, onto a second molecule of allyl halide [55, 56]. 

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