Allylic nucleophilic displacement

Abstraction of laterally situated protons followed by allylic nucleophilic displacement of ROH... 

Special cases (i) Allylic nucleophilic displacement SJ and Sn,2 (ii) Aryl (PhX) and vinylic (R2C=CRX) halides these are generally unreactive towards nucleophilic displacement, although benzylic (PhCH2X) and allylic (RCH = CHCH2X) are more reactive. 

Similar processes, both direct and allylic nucleophilic displacements, are observed when hexopyranose thioglycosides bearing a pyrimidine ring on the 6-OH group are activated with DMTS (eq 29). 2... 

Three selective methods to remove protective groups are receiving much attention assisted, electrolytic, and photolytic removal. Four examples illustrate assisted removal of a protective group. A stable allyl group can be converted to a labile vinyl ether group (eq. 4) a /3-haloethoxy (eq. 5) or a /3-silylethoxy (eq. 6) derivative is cleaved by attack at the /3-substituent and a stable o-nitro-phenyl derivative can be reduced to the o-amino compound, which undergoes cleavage by nucleophilic displacement (eq. 7) ° ... 

Interestingly, the photolysis of methyl 3-azido-2.6-difluorobenzoate (61) in diethylamine yields, in addition to the two expected 3//-azepines 62 and 63, a third azepine 64 formed by nucleophilic displacement of allylic fluorine from the 3-position by diethylamine.188 Displacement of allylic halogen from haloazepines has been noted previously.177... 

Bordwell and Cooper211 drew attention to the inertness of a-halosulfones and related compounds towards nucleophilic displacements of the halogen. Thus chloromethyl p-tolyl sulfone reacts with potassium iodide in acetone at less than one-fiftieth of the rate for n-butyl chloride. On the other hand, l-(p-toluenesulfonyl)-3-chloro-l-propene reacts about 14 times faster than allyl chloride. This contrast (and other comparisons) led the authors to attribute the inertness of a-halosulfones to steric hindrance, which was eliminated when the sulfonyl group was more remote from the reaction center. 

Pathway A shows the most common reaction where the nucleophilic substitution reaction occurs at the electron-deficient carbon atom due to the strong electron-attracting character of the sulfonyl group. Nucleophilic displacements at the allylic position (SN2 reaction) are shown in pathway B. Pathway C is the formation of a-sulfonyl carbanion by nucleophilic attack on the carbon atom p to the sulfone moiety. There are relatively few reports on substitution reactions where nucleophiles attack the sulfone functionality and displace a carbanion as illustrated in pathway D3. 

A very mild method that is useful for compounds that are prone to allylic rearrangement involves prior conversion of the alcohol to the tosylate, followed by nucleophilic displacement with halide ion. 

An explanation not easily distinguishable from the one involving resonance with a carbonium ion structure in the transition state is that the reactive species is an ion pair in equilibrium with the covalent molecule. This is quite likely in a solvent insufficiently polar to cause dissociation of the ion pairs. Examples of second order nucleophilic displacements accelerated by the sort of structural change that would stabilize a carbonium ion are of fairly frequent occurrence. Allyl chloride reacts with potassium iodide in acetone at 50° seventy-nine times as fast as does -butyl chloride.209 Another example is the reaction of 3,4-epoxy-1 -butene with methoxide ion.210... 

Acetylation occurs at the 2-position of allene systems (Scheme 8.14). The intermediate 7t-allyl complex breaks down via the nucleophilic displacement of the cobalt carbonyl group by the hydroxide ion to produce the hydroxyketone (7) [ 11 ]. An alternative oxygen-initiated radical decomposition of the complex cannot, however, be totally precluded. The formation of a second major product, the divinyl ketone (8), probably arises from direct interaction of the dicobalt octacarbonyl with the allene and does not require the basic conditions. 

Acid-induced mcemization and isomerization of chiral allylic alcohols. Bimolecular nucleophilic displacements in allylic compounds are known to proceed via the four possible pathways shown in Scheme 19. 

Allylic diacetates were converted into N,N, 0,0, and N, O-heterocycles in a palladium catalyzed two step nucleophilic displacement sequence. The reaction of o-aminophenol and cyclopentenyl-diacetate, for example, gave the cyclopentene condensed phenoxazine derivative in acceptable yield (4.21.), while o-phenylenediamine and catechol gave the corresponding phenazine and dioxine derivative in good yield.24... 

Reactivities comparable to allylic halides are found in the nucleophilic displacement reactions of benzylic halides by SN1 and SN2 mechanisms (Table 14-6). The ability of the benzylic halides to undergo SK1 reactions clearly is related to the stability of the resulting benzylic cations, the electrons of which are extensively delocalized. Thus, for phenylmethyl chloride,... 

Cyclization of allylic alcohols to form epoxides has been particularly problematical, and the reactions have been more of mechanistic than of synthetic interest. For reactions conducted under basic conditions, it is possible that epoxide formation involves initial halogen addition followed by nucleophilic displacement to form the epoxide. Early examples of direct formation of epoxides from allylic alcohols with sodium hypobromite," bromine and 1.5 M NaOH,12 and r-butyl hypochlorite13 have been reviewed previously.fr Recently it has been shown that allylic alcohols can be cyclized effectively with bis(jym-collidine)iodine(I) perchlorate (equation 3).14 An unusual example of epoxide formation competing with other cyclization types is shown in equation (4).15 In this case, an allylic benzyl ether competes effectively with a -/-hydroxyl group as the nucleophile. 

Dicarbonates of enediols have been converted to conjugated dienes on treatment with Pd° catalysts. Nucleophilic displacement of the allyl carbonate by an V-allyl complex may be responsible (equation 122).321... 

The SN21 reaction can theoretically take place by a nucleophilic attack on the allylic system either syn or anti to the leaving group (cf. 79 and 80). Although he never fully elaborated on it in print, Winstein (24-26) was the first to postulate that the nucleophilic attack should be syn. He suggested that the approach of the nucleophile displaces the n electrons in such a direction as to allow them to attack the C—X bond from the rear. The syn attack would therefore be favored for stereoelectronic reasons. 

It has been established that complex hydrides react via nucleophilic displacement of either vinylic or allylic halogen by hydrogen [121-124] (Scheme 57). 

Because of the ability of some leaving groups to stabilize an a-carbanion, the pH at which the substitution is performed can be critical. Electrophiles with such leaving groups (e.g. R-N02 [36, 37], R-S(=0)2R [38, 39], R-S(=O)R[40]) will usually undergo substitution only under neutral or acidic conditions, what limits the choice of suitable nucleophiles. Some nucleophilic displacements of nitro and sulfonyl groups, both under acidic and basic reaction conditions, are shown in Schemes 4.6 and 4.7. Allylic nitro groups can also be readily displaced by catalysis with palla-... 

---