Allyl bromide nitrile from

Organozinc reagent prepared from the 2-(trimethylsilyl)allyl bromide 156 and zinc react with alkynes or carbonyl compounds as well as nitriles to give the corresponding coupling products in moderate to good yields (equation 130)225. 

We shall end this section with a beautiful illustration of an intramolecular 1,3-dipolar cycloaddition of a nitrile oxide that was used in the synthesis ofthe vitamin biotin. Starting at the beginning of the synthesis will allow you to revise some reactions from earlier chapters. The starting material is a simple cyclic allylic bromide that undergoes an efficient 5 2 reaction with a sulfur nucleophile. In fact, we don t know (or care ) whether this is an 5 2 or S 2 reaction as the product of both reactions is the same. This sort of chemistry was discussed in Chapter 23 if you need to check up on it. Notice that it is the sulfur atom that does the attack—it is the soft end of the nucleophile and better at Sn2 reactions. The next step is the hydrolysis ofthe ester group to reveal the thiolate anion. 

Bromomethyl)isoxazolines, prepared from a nitrile oxide and an allyl bromide, may be reductively ring opened to y-enoximes XIV) XIV may be reduced in aqueous THF with Al(Hg) to the homoallylamine (XV), as in Eq. (6) [98] ... 

Eliminations. Unsaturated oximes are obtained from 5-bromomethylisoxazolidines that are the cycloadducts of nitrile oxides with allyl bromide. At temperature >0°, the double bond moves to conjugation with the oxime. ... 

Table 3.19. Results from Barbier-type reactions of allylic bromides and organic nitriles with Zn/Ag [104]...

An interesting new route to %5-unsaturated a-amino-acids involves ring cleavage of 2-isoxazolines prepared from allyl bromides and nitrile oxides (Scheme 51). The prospects of extending this process to other substrates seem to be good. 

Li and coworkers reported the conjugate addition of alkyl groups to enamides mediated by zinc in aq. NH4CI to generate a -amino acid derivatives (Eq. 4.73). No reaction was observed in the absence of water. Both secondary and tertiary alkyl groups such as linear (2-butyl, 2-propyl, 2-pentyl), cyclic (cyclohexyl, cyclopentyl, cycloheptyl), and bulky ones (tert-butyl) were all transferred to the substrate successfully. Even simple primary iodides and methyl iodide provided the desired products in good yields. Miyabe et al. as well as Jang and Cho reported the addition of alkyl radicals from alkyl iodide to a,p unsaturated ketones, esters, and nitriles mediated by indium in aqueous media. Indium-mediated Michael addition of allyl bromide to l,l-dicyano-2-arylethenes also proceeded well in aqueous medium. ... 

The conversion of the polystyrene-supported selenyl bromide 289 into the corresponding acid 290 allowed dicyclohexylcarbodiimide (DCC)-mediated coupling with an amidoxime to give the 1,2,4-oxadiazolyl-substituted selenium resin 291 (Scheme 48). Reaction with lithium diisopropylamide (LDA) and allylation gave the a-sub-stituted selenium resin 292, which was then used as an alkene substrate for 1,3-dipolar cycloaddition with nitrile oxides. Cleavage of heterocycles 293 from the resin was executed in an elegant manner via selenoxide syn-elimination from the resin <2005JC0726>. 

Allyl alcohols readily react with trichloroacetonitrile to give the corresponding trichloroacetimidates 145. Activation of the double bond with electrophilic reagents results in ring closure to yield oxazolines 146. The most commonly employed electrophiles include iodine, iodine monochloride, phenylselenyl chloride, and mercuric trifluoroacetate. Other nitriles including cyanogen bromide and N,N-dimethylcyanamide can also be used. Since oxazolines readily hydrolyze to amides, the net effect of this reaction sequence is to produce p-amino alcohols 147 from an allyl alcohol. This strategy has been employed in numerous total syntheses of natural products. Examples are listed in Table 8.18 (Fig. 8.7 Scheme 8.43). ° ... 

Alkyl halides (particularly bromides) undergo oxidative addition with activated copper powder, prepared from Cu(I) salts with lithium naphthalenide, to give alkylcopper species10. The alkyl halides may be functionalized with ester, nitrile and chloro functions ketone and epoxide functions may also be tolerated in some cases11. The resulting alkylcopper species have been shown to react efficiently with acid chlorides, enones (conjugate addition) and (less efficiently) with primary alkyl iodides and allylic and benzylic bromides (equations 5 and 6). If a suitable ring size can be made, intramolecular reactions with epoxides and ketones are realized. 

Tt-Allylnickel halides. Billington has reviewed the preparation of these complexes from allylic halides using Ni(CO)4 or Ni(COD)2, and their use in synthesis, mainly of natural products (54 references). These complexes react with a wide range of both aliphatic and aryl bromides or iodides as well as aldehydes, ketones, epoxides, and quinones. One advantage is that both allyl ligands react. They do not react with acid chlorides, esters, ethers, nitriles, or acetals. 

As an alternative to electrophilic substitution as a means for introducing functional groups into the calixarenes, a reaction sequence has been developed that involves the conversion of calix[4]arene (59) to the tetraallyl ether 63. When 63 is heated in diethylaniline it undergoes a four-fold p-Claisen rearrangement to afford p-allyl-calix[4]arene (62) in excellent yield 126). From the tetra-tosyl ester of 62 (i.e. compound 66 a) a variety of functionalized calixarenes have been obtained, including the aldehyde 66b, alcohol <56 c, bromide 66 d, azide 66 e, amine 66f, and nitrile 66g. Removal of the tosyl group occurs under mildly basic conditions to yield, for example, p-(2-hydroxyethyl)calix[4]arene (66 h). 

There is one more way for conversion of ort/to-nitroarylacetonitriles into indoles. Alkylation of such nitriles with allyl or benzyl halides followed by treatment of the compounds obtained with basic agents results in a multistep transformation, which is likely to proceed via intermediate nitrosoarenes, to produce 1-hydroxyindoles. For instance, alkylation of ort/io-nitroarylacetonitriles with 3-phenylallyl bromide gives the compounds that in the presence of chlorotri-methylsilane and triethylamine undergo cyclization into 3-cyano-l-hydroxy-2-vinylindoles (Scheme 70) [188]. Presumably, this reaction proceeds via 0-silylation of the nitronate anion and 1,5-elimination of trimethylsilanol from the intermediate trimethylsilyl nitronate, followed by cyclization and a hydrogen shift. 

Tertiary amines are also known to effect the phase transfer addition of cyanide ion to primary, allylic, and benzylic halides [9]. The reported effect of amine structure on catalytic efficiency closely parallels that reported by Hennis for ester formation in a two-phase system (see Sect. 1.7). Both the nitrogen of the amine and the carbon bearing halide of the alkyl bromide must be sterically accessible for the reaction to succeed. Thus, -hexylamine is effective in concert with -butyl bromide but the combinations of either 5-butyl bromide and -hexylamine or -butyl bromide and cyclohexylamine are not. Tertiary amines are generally more effective than secondary or primary amines. In addition, the yields of primary nitriles decrease dramatically with the size of the primary alkyl bromide from quantitative with n-butyl to only 6% with -decyl bromide when -hexylamine is used as phase transfer catalyst. On the other hand, tributylamine was equally useful as a catalyst for the quantitative conversion of either 1-bromohexane or 1-bromodecane to the corresponding nitriles [9]. In general, these observations accord with those of Hennis and coworkers indicating that this reaction is an example of in situ formation of and catalysis by quaternary ammonium salts [10]. 

---