Allylic chlorides nucleophilic substitution

The allyl-substituted cyclopentadiene 122 was prepared by the reaction of cyclopentadiene anion with allylic acetates[83], Allyl chloride reacts with carbon nucleophiles without Pd catalyst, but sometimes Pd catalyst accelerates the reaction of allylic chlorides and gives higher selectivity. As an example, allylation of the anion of 6,6-dimethylfulvene 123 with allyl chloride proceeded regioselectively at the methyl group, yielding 124[84]. The uncatalyzed reaction was not selective. 

Allyl chloride is quite reactive toward nucleophilic substitutions, especially those that proceed by the Sn2 mechanism, and is used as a starting material in the synthesis of a variety of drugs and agricultural and industrial chemicals. 

The objective in selecting the reaction conditions for a preparative nucleophilic substitution is to enhance the mutual reactivity of the leaving group and nucleophile so that the desired substitution occurs at a convenient rate and with minimal competition from other possible reactions. The generalized order of leaving-group reactivity RSOj" I- > BF > CF pertains for most Sw2 processes. (See Section 4.2.3 of Part A for more complete data.) Mesylates, tosylates, iodides, and bromides are all widely used in synthesis. Chlorides usually react rather slowly, except in especially reactive systems, such as allyl and benzyl. 

The addition of an allyl metal to a-amino aldehydes has been used by Vara Prasad and Rich (Scheme 12)J23l After the addition step, the allyl group is oxidized to a carboxylic acid and lactonized. Then, the a-carbon of the lactone is alkylated stereoselectively. These investigators also systematically examined the addition reaction to determine its diastereo-selectivity. The highest diastereoselectivity was obtained when allyltrimethylsilane was used in the presence of tin(IV) chloride. An increase in the steric bulk of the protecting group and of the side chain also resulted in a better diastereoselection. Alternatively, Taddei and co-workers 24-26 used a 2-(halomethyl)allylsilane and the side chains were introduced by nucleophilic substitution of the halogen (Scheme 13). 

The reaction is a nucleophilic substitution in which the nucleophile (C6H5S ) becomes attached to the carbon that bore the chloride leaving group. Allylic rearrangement is not observed therefore, it is reasonable to conclude that an allylic carbocation is not involved. The mechanism is SN2. 

The reaction that leads to allylamine is nucleophilic substitution by ammonia on allyl chloride. 

It is well-established that 7r-allylpalladium is electrophilic, and no reaction with electrophiles has been observed. However, there is an evidence that bis-7r-allylpalladium (172), generated in situ, could be amphiphilic. Typically, formation of the 2-substituted 3,6-divinylpyran (175) by the reaction of butadiene with aldehyde can be explained by the amphiphilic nature of the bis-7r-allylpalladium 173 generated in situ as an intermediate, which reacts with the electrophilic carbon and the nucleophilic oxygen in the aldehyde as shown by 174 [86]. As a similar reaction, piperidone is obtained by the reaction of butadiene with isocyanate [87]. The reaction of allyltributylstannane (176), allyl chloride and benzalmalononitrile (177) in the presence of PdCl2(Ph3P)2 (3 mol %) afforded the diallylated product 178 in high yield. 

The 5n2 reactions of y-substituted allyl chlorides where the nucleophile is a free anion and an ion pair were studied theoretically at the HF/6-31+G level of theory.10 The calculations showed that the free ion, S N2 reaction proceeds through a transition state (7) with significant positive charge on Ca and little conjugation with the n-system. Placing substituents on Cy of the free ion reactions gave computed Hammett p values of -3.3 and -4.6 for the trans- and ds-conformation reactions, respectively. The transition states (8) for the ion pair reactions, on the other hand, have considerable positive charge on both Ca and Cy and the computed Hammett p value is +18.8. 

The known reactions of the perfluoroalkylsilver derivatives generally equate to nucleophilic substitution reactions and the oxidative perfluoroorganylation of group 12-16 elements.39,40 Normant and coworkers have reported the reaction of both carbon dioxide and allyl bromide with perfluoroisopropylsilver (Scheme l.ll).41 Heptafluoro-2-nitrosopropane has been prepared in good yield from perfluoroisopropylsilver by treatment with nitrosyl chloride.42... 

Allylic amination of allyl halides can also be achieved using lithium and potassium bis(trimethylsilyl)amides [34] and potassium 1,1,3,3-tetramethyldisilazide [35] as the nucleophiles. It has been found that for the reaction of alkyl-substituted allyl chlorides using lithium bis(trimethylsilyl)amides as the nucleophile the allylic amination proceeds smoothly in a SN2 fashion to give /V,Af-disilylamines in high yields when silver(I) iodide was used as an additive. Other metal complexes such as copper ) iodide and other silver(I) salts can also be used as additives for the reaction. 

The nucleophilic photosubstitution reactions of the nitro-substituted allylic bromide 13128 and allylic chloride 14129 with nitronate anion (equations 25 and 26) occur via a photo-induced radical-chain substitution process. Apparently, the allyl radical intermediate in... 

An important recent advance in the area is the demonstration that allyl chlorides readily form allylcopper species upon exposure to highly activated copper ( Rieke copper ). The resultant allylcoppers have been shown to react with a fairly wide range of nucleophiles (ketones, aldehydes, acid chlorides, enones, epoxides [after conversion to the cuprate], imines, and allyl bromides)56. Regiochemical considerations in such substitutions depend upon the cases studied, and are fairly complex. The allylcoppers formed have, in all cases, the least substituted C—Cu bond allyl transfer from these reagents is selective from the imposition of the allyl (enone electrophiles excepted)(equations 41 and 42). The allyl chloride... 

Propene is readily monochlorinated to allyl chloride, and the reactive Cl undergoes nucleophilic substitution with NH3. 

S-Orthoesters seldom appear in organic synthesis but they do occupy one useful niche. In 1967 Seebach245-246 introduced tris(methylthio)methyhithium as an acyl anion equivalent of a carboxyl group. It was sufficiently stable and nucleophilic to react with a range of electrophiles. For example, nucleophilic substitution of the allylic chloride 121,1, followed by mercury(Il)-mediated hydrolysis of the SS-orthoester intermediate 121,2, gives the p,y-unsaturated car-... 

The following two steps are used to transform the primary allylic chloride 47 into the corresponding primary allylic alcohol 23. Nucleophilic substitution of the chloride with CsOAc gives an acetate which is then saponified under basic conditions to form alcohol 23 and methyl acetate. 

Most of the early mechanistic studies that focused on the S ,j2 versus 8 2 nucleophilic substitution by an organometallic reagent were made with allylic halides. In the late 1940s, Wilson [7] showed that phenylmagnesium bromide reacted with a- and y-methylallyl chlorides 1 and 2, respectively, to afford a nearly identical mixture of primary and secondary substituted products 3 and 4, respectively, in a 75 25 ratio [Eq. (1)]. 

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