Nucleophilic additions carbanion intermediates, alkenes

What can follow with an alkene is an ionic chain reaction with the following two propagating steps. First, the nucleophile attacks at carbon to form a carbon anion (carbanion) intermediate (Equation 10-8). Second, electrophilic transfer of a proton from HX to the carbanion forms the adduct and regenerates the nucleophile (Equation 10-9). The overall reaction is the addition of HX to the double bond ... 

Reactions which are apparently stereospecific occur in the nucleophilic displacement of vinylic iodide [31] in the electron-deficient alkenes E- and Z-24 shown in Scheme 9.14. With ethanolic toluenethiolate, the sole detectable product from the reaction of -24 is -25. However, -25 is also the sole detectable product from the reaction of Z-24. This stereoconvergence demands that the stereoisomers react through a common intermediate, and it was reasonably suggested that initial nucleophilic addition of the thiolate anion yields a resonance-stabilised carbanion (26) whose stereoisomerisation, again by rotation about a carbon-carbon single bond, is much faster than the loss of iodide to yield the substitution product ( fy). 

The fruitfulness of the idea of a stepwise addition with an independent variation of the addends was brilliantly illustrated by Normant s studies, which resulted in the elaboration of a general method of alkene synthesis based on the reaction of alkyne carbometallation. Basically this reaction represents a case of the well-known nucleophilic addition to a carbon-carbon triple bond. In the Normant reaction, however, the initial addition of a nucleophile (an organome-tallic reagent) across the triple bond results in the formation of a stabilized carbanion-like intermediate equivalent to a vinyl carbanion. This intermediate can similarly be further reacted with an external electrophile. Most typically, copper-modified Mg or Li reagents, which are unable to react with acidic acetylenic hydrogens, are used in this sequence. 

Nucleophilic additions to alkenes and alkynes are also possible, but these reactions generally require that the substrate have substituents that can stabilize a carbanionic intermediate. Therefore, nucleophilic additions are most likely for compoimds with carbon-heteroatom multiple bonds, such as carbonyl compounds, imines, and cyano compounds. We may distinguish two main types of substituents that activate alkenes and alkynes for nucleophilic attack. The first type consists of those activating groups (labeled AG in equation 9.79) that can stabilize an adjacent carbanion by induction. ... 

The previously accepted pathway consisted of P-H oxidative addition to Pt(0) to form 19 followed by coordination and insertion of the alkene in the Pt-P bond to form 20 and a final reductive elimination to furnish the product and regenerate the catalyst. Another possibility is the nucleophilic attack of phosphido complex 19 to the alkene ( Michael addition mechanism, as in anionic polymerisation) to generate the zwitterionic intermediate 21. This complex can yield the hydrophosphination product 11 via one of two complementary pathways. Carbanion attack at the cationic platinum hydride i.e. intramolecular hydrogen transfer) would yield the final phosphine complexed to Pt(0) that would be displaced by an equivalent of PHR R to furnish, after oxidative addition, starting complex 19. Alternatively, the anionic carbon atom in 21 could attack the platinum centre directly, forming the cyclic intermediate 22. From here Pt-P bond dissociation would generate 20, which would furnish the product after reductive elimination. 

We noted in this chapter that nucleophilic addition to alkenes occurs when groups capable of electron withdrawal by both induction and resonance are attached to the alkene. The addition of alkoxide anions to 2,2-dichloro-l,l-difluoroethylene occurs on the carbon with the fl uorines. Why does the addition occur to place the negative charge of the carbanion intermediate on the carbon with the chlorines, rather than on the carbon with the more electronegative fluorines ... 

As indicated vide supra), the classical mechanism for the Wittig reaction involves the initial nucleophilic addition of the ylide carbanion (resonance structures 1 and 2) to the electrophilic carbon of the carbonyl in 3 to afford betaine intermediate 4. Rotation about the central C-C bond provides for ring closure to 1,2-oxaphosphetane 5. These species are thermally unstable and readily decompose, via a concerted electrocyclic process, to generate the corresponding phosphine oxide 8 and the ( )-alkene 6 or (Z)-alkene 7. 

The intramolecular addition of carbon nucleophiles to alkenes has received comparatively little attention relative to heterocyclization reactions. The first examples of Pd-catalyzed oxidative carbocyclization reactions were described by Backvall and coworkers [164-166]. Conjugaled dienes with appended al-lyl silane and stabilized carbanion nucleophiles undergo 1,4-carbochlorination (Eq. 36) and carboacetoxylation (Eq. 37), respectively. The former reaction employs BQ as the stoichiometric oxidant, whereas the latter uses O2. The authors do not describe efforts to use molecular oxygen in the reaction with allyl silanes however, BQ was cited as being imsuccessful in the reaction with stabihzed car-banions. Benzoquinone is known to activate Ti-allyl-Pd intermediates toward nucleophilic attack (see below. Sect. 4.4). In the absence of BQ, -hydride eUm-ination occurs to form diene 43 in competition with attack of acetate on the intermediate jr-allyl-Pd" species to form the 1,4-addition product 44. 

Nucleophilic Aromatic Substitution. A natural extension of alkene addition processes is aromatic nucleophilic substimtion. Again, the ease of the process is highly dependent on the stability of the intermediate carbanion and strong EWGs are needed to facilitate these reactions in solution. The classic example is the... 

The intermediate carbanion from addition of CN to an alkyne has the unshared electron pair on an sp -hybridized C. It is more stable and is formed more readily than the rp -hybridized carbanion formed from a nucleophile and an alkene. 

Unsaturated fluorinated compounds are fundamentally different from those of hydrocarbon chemistry. Whereas conventional alkenes are electron rich at the double bond, fluoroal-kenes suffer from a deficiency of electrons due to the negative inductive effect. Therefore, fluoroalkenes react smoothly in a very typical way with oxygen, sulfur, nitrogen and carbon nucleophiles.31 Usually, the reaction path of the addition or addition-elimination reaction goes through an intermediate carbanion. The reaction conditions decide whether the product is saturated or unsaturated and if vinylic or allylic substitution is required. Highly branched fluoroalkenes, obtained from the fluoride-initiated ionic oligomerization of tetrafluoroethene or hexafluoropropene, are different and more complex in their reactions and reactivities. 

Nucleophiles can be added to acceptor-substituted alkenes. In that case, enolates and other stabilized carbanions occur as intermediates. Reactions of this type are discussed in this book only in connection with 1,4-additions of organometallic compounds (Section 10.6), or enolates (Section 13.6) to a,/J-unsaturated carbonyl and carboxyl compounds. 

Some authors have described the generation of boronates and stannanes bound to a support starting from the corresponding aryl haHdes [372, 6]. Boranes, boronic esters, and stannanes can furthermore be readily obtained from vinyl halides or from alkenes or alkynes by means of hydroboration or hydrostannylation (see Section 4.2). Boronates and silanes or stannanes can act as carbanion equivalents. Thus, support-bound boronates can release aryl alkenyl groups upon transmetala-tion to Rh. The intermediately formed Rh species can act as nucleophiles, and react with aldehydes to give alcohols (618) or can perform Michael additions (621, 622) [437, 438, 439] (Scheme 129) (see also Sections 4.7.15 and 4.2). 

We know how stabilized carbanions such as enols and enolated enamines are key intermediates in biological isomerization reactions and in carbon-carbon bond-forming and bond-breaking events. In this chapter, we will look at two more important reaction types, called Michael additions and -eliminations, which involve stabilized carbanion species as intermediates. In a Michael addition, a nucleophile and a proton are added to the two carbons of an alkene that is conjugated to a carbonyl group. The reverse of a Michael addition is called a -elimination. 

The mechanism involves addition of the carbanion nucleophile to the electrophilic carbon of the carbonyl, followed by a breakdown of the resulting oxa-phosphetane intermediate. A molecule of triphenylphosphine oxide (Ph3P=0) is generated along with the alkene product. 

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