Allylic carbon, nucleophilic displacement

Another common reaction of alkenes uses diatomic halogens such as bromine (Br2) to form 1,2-dibromides (see Chapter 10, Section 10.4.1). In this reaction, the alkene reacts as a Lewis base with the bromine atom to form a bromonium ion. When 1,3-butadiene (3) reacts with bromine, both 1,2 and 1,4 addition products are formed, just as with the HBr reaction. The products are 3,4-dibromo-l-butene (32) and a mixture otE- and Z-l,4-dibromo-2-butene (33 and 34). Initial reaction with bromine gives bromonium ion 29 however, when this reacts with bromide ion, there are two sites for reaction. If bromide attacks the less stericaUy hindered carbon atom, the product is 32, but the bromine ion may also attack the C=C unit to give products 33 + 34. Nucleophilic attack of this type is called an Sj reaction (nudeophilic substitution at an allylic carbon with displacement of the leaving group). 

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. 

Efforts to cause the carbon nucleophile available at C-2 (carbohydrate numbering) of the osulose derivative 66 to displace the methoxy group with allylic rearrangement and with consequent formation of a tricyclic product by use of Pd(0) catalysts [34] were unsuccessful, but the intended reaction proceeds "smoothly when tin(IV) chloride is used together with acetic anhydride in dichloromethane. Clearly, the Lewis acid activates the allylic ether group, and the C-2 nucleophile effects its displacement. Concurrently, acetolysis of the benzylidene ring occurs and the product isolated is the cu-decalin analogue 67 [33],... 

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... 

Loss of stereospecificity in the addition of soft carbon nucleophiles can occur if the rate of nucleophilic attack is slow, due, for example, to extreme steric bulk, e.g. NaCH(SChPh>2,167 of the nucleophile (equation 154). In this case, the initially displaced OAc has sufficient time to return and attack the ir-allyl complex. Acetate anions (vide infra) are capable of either ligand or metal addition, thus scrambling the stereochemistry of the starting allyl acetate. 

Allylic carbonates produce the required alkoxide by decarboxylation of the carbonate anion that is displaced in the formation of the 7E-allyl palladium intermediate. Deprotonation creates the active nucleophile, which rapidly traps the 7t-allyl palladium complex to give the allylated product and regenerates the palladium(O) catalyst. 

Mechanistically, this homobimetallic catalytic process can be described and rationalized as a Pd(0)-catalyzed deprotection of the phenyl allylether 97 furnishing phenolate 99 that now can enter the second Pd(II)-catalyzed cycle (Scheme 34). The destiny of the 7r-allyl-Pd complex is a carbonyl insertion to furnish, after nucleophilic displacement with methanol, but-3-enoic acid methyl ester and hydroiodic acid. The phenolate 99 cyclizes to give a vinyl-Pd species that inserts carbon monoxide followed by the attack of methanol. 

Structures I and II differ only in the lactonic C-O bond. This seemingly simple transformation conceals complications derived from the oxidative process involved in the formation of this bond. Necessarily, the oxidant must be an external agent since the enone II does not show the traces (reduced fragments) that are always produced during any intramolecular redox operation. This oxidizing agent in all probability is bromine. In fact, one could predict, in the absence of any further evidence, that the reaction mechanism must proceed by way of an allylic bromination at the 7 carbon of enone I, which would provide the required functionalization for an intramolecular nucleophilic displacement of bromide by the carboxylate anion in a second step. This is shown in structure... 

Whenever you see retention of stereochemistry, you should think double inversion, and in fact double inversion occurs in this reaction. The Pd(0) complex acts as a nucleophile toward the allylic carbonate or acetate, displacing MeOCC>2 or AcO by backside attack and giving an allylpalladium(II) complex. The nucleophile then attacks the allylpalladium(II) complex, displacing Pd by backside attack to give the product and regenerate Pd(0). The regio-chemistry of attack (Sn2 or Sn2 ) is dependent on the structure of the substrate. 

Both ( )- and (Z)-allyl dithiocarbamates have been stereoselectively prepared in high yields from acetates of MBH adduets in catalyst-free one-pot three-component coupling reactions of carbon disulfide and amine in water under a mild and green procedure (Scheme 3.152). The reaction pathway involves the nucleophilic displacement (-S n2 ) of MBH acetates by dithio-carbamate anions. The utility of these allyl dithiocarbamates has been demonstrated in the synthesis of 3,5-dibenzyl-l,3-thiazines derivatives 344 and 345 (Scheme 3.153). ... 

The Pd-catalysed allylation of carbon nucleophiles with allylic compounds via Jt-aUylpaUadium complexes is called the Tsuji-Trost reaction [32]. Typically, an allyl acetate or carbonate (54) reacts with a Pd-catalyst resulting in displacement of the leaving group to generate a Jt-allylpalladium complex (55) that can undergo substitution by a nucleophile (56) (Scheme 4.14). In 1965, Tsuji reported the reaction of ti-aUylpaUadium chloride with nucleophiles such as enamines and anions of diethyl malonate and ethyl acetoacetate. A catalytic variant was soon reported thereafter in the synthesis of allylic amines [33]. In 1973, Trost described the alkylation of alkyl-substituted 7i-aUylpalladium complexes with methyl methylsulfonylacetate... 

The proposed catalytic cycle starts by coordination of rhodium to both the oxygen and alkene component of the vinyl epoxide, forming complex 69, followed by oxidative insertion of rhodium into the allylic carbon-oxygen bond with retention of stereochemistry (Scheme 10.28). The initially formed Rh species 70 undergoes isomerization via the Jt-allyl Rh " complex 71 to the less strained species 72. Subsequent intermolecular nucleophilic Sn2 displacement with inversion affords the observed product 73 with concomitant release of Rh . 

Nucleophilic Displacement. PhTMS-BF3 0Et2 system has been shown to be useful in the transformation of allylic alcohols to allylic sulfides (eq IS). Preparation of unsymmetrical diaryl sulfides can be achieved by reaction of arenediazonium tetraflu-oroborates with PhSTMS (eq 19). In some cases, addition of cupric sulfide increases the yield of the diaryl sulfides. The use of (phenylthio)trimethylsilane as a coupling partner in palladium catalyzed reactions with aUyl carbonates (eq 20) and aryl iodide (eq 21) has been explored. ... 

Sn2 reactions of allylic halides with good nucleophiles (Section 6-8) are faster than those of the corresponding saturated haloalkanes. Two factors contribute to this acceleration. One is that the allylic carbon is attached to a relatively electron-withdrawing sp hybridized carbon (as opposed to sp Section 13-2), making it more electrophilic. The second is that overlap between the double bond and the p orbital in the transition state of the Sn2 displacement (see Figure 6-4) is stabilizing, resulting in a relatively low activation barrier. 

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