Addition to unactivated double bonds

The cyclization is highly stereoselective according to Beckwith s radical cyclization rules [73]. Thus, the allylic benzyl ether 41 (a 1 1 mixture of diastereoisomers) undergoes a 

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In this section we consider only addition to unactivated double bonds. Addition of amines to nitrothiophenes will be discussed in Section 3.14.3.5. 

Anodic addition is a valuable preparative method since nucleophiles can be oxidatively added to unactivated double bonds. The manifold of synthetic subunits in the class of anions is thus no longer limited to use in nucleophilic reactions, but can be equally well applied in radical or electrophilic additions, whereby the choice of reagents for these reactions is considerably extended. 

The insertion reactions into cyclohexane C H bonds (Table 1) give some idea of which nitteties give synthetically useful yields. However, since most other substrates will contain more than one sort of C—bond, it is important to know the selectivity of nitrenes for different types of C—bond. Several snidies of nitrene selectivity towards tertiary, secondary and primary unactivated C—H bonds have been made, although attempts to study allylic C—insertion reactions are complicated by the competing nitrene addition to the double bond. In cyclohexene it has been estimated that the allylic C—bond is only about three times more reactive than the homoallylic C—H bond towards insertion of ethoxycarbo-nylnitrene. However, the reaction is totally unsatisfactory as a means of allylic fhnctionalization since, as shown in Scheme 3, the yields are so low. 

Unactivated double bonds do not react readily with nucleophiles. However, additions are observed if the olefin is coordinated to a transition metal many organometallic complexes are known which induce such reactions (263). While this aspect has not been explored with strained olefins, a few examples of direct nucleophilic additions to distorted double bonds have been reported. 

Diamines.- The preparation of vicinal diamines by functionalisation of olefins remains an area of active research interest. Full details concerning a previously reported synthesis of vic-primary diamines via -bromosuccinimide-mediated addition of cyanamide to unactivated double bonds followed by formation and subsequent hydrolysis of a 2-ethoxyimidazoline have been published. 

Conjugate addition of organometals and enol ethers to a,fS-unsaturated carbonyl compounds is one of the backbones in organic synthesis. A less common approach is the use of free radicals, which also add to unactivated double bonds. However, the regiocontrol of such additions is best achieved by means of electronically withdrawing groups (such as carbonyls, nitriles, sulfones, and nitro), which direct the radical attack to the fi-position. 

The problem of terminal addition (anti-Markovnikov) of HCN to isolated unactivated double bonds was not solved until carbon monoxide-free, low-valent transition metal complexes became available. During the mid 1960s, W. C. Drinkard allowed 1-hexene to react with HCN in the presence of tetrakis(triethylphosphite)nickel(0) and the resulting product mixture contained a small amount of the terminal addition product n-heptanenitrile, and Drinkard and Lindsey found that the reaction with 3-pentenenitrile produced ADN (7). 

Kirby, A. J., Logan, C. J. Addition of amine nitrogen to an unactivated double bond. The mechanisms of the reverse Hofmann elimination. J. Chem. Soc., Perkin Trans. 2 1978, 642-648. 

Addition of sulfinic acids (or salts) to unactivated C=C double bonds 172... 

Addition of suifinic acids (or sails) to unactivated C—C double bonds... 

A surprising exception has been reported with evidence for a cleavage reaction in the case of divinyl sulphone. In non-aqueous and slightly acidic media, the behaviour of a., ji-unsaturated aromatic sulphones is also complex (see Table 7) since the cleavage and the saturation may compete. Strongly electrophilic double bonds undergo Michael additions in aprotic solvents by slowly protonated anions. Transfer of labile hydrogen may also lead to unactivated bases. It is noteworthy that in numerous cases (Table 6) the saturation is the preferred route. 

Organotin hydrides add across carbon-carbon triple bonds even more easily than they add across carbon-carbon double bonds. For example, the addition to the unactivated C=C bond of phenylacetylene proceeds spontaneously at 20 °C without an initiator (equation 88), whereas the addition to an unactivated olefin requires the presence of an initiator118. 

Hosokawa, Murahashi, and coworkers demonstrated the ability of Pd" to catalyze the oxidative conjugate addition of amide and carbamate nucleophiles to electron-deficient alkenes (Eq. 42) [177]. Approximately 10 years later, Stahl and coworkers discovered that Pd-catalyzed oxidative amination of styrene proceeds with either Markovnikov or anti-Markovnikov regioselectivity. The preferred isomer is dictated by the presence or absence of a Bronsted base (e.g., triethylamine or acetate), respectively (Scheme 12) [178,179]. Both of these reaction classes employ O2 as the stoichiometric oxidant, but optimal conditions include a copper cocatalyst. More recently, Stahl and coworkers found that the oxidative amination of unactivated alkyl olefins proceeds most effectively in the absence of a copper cocatalyst (Eq. 43) [180]. In the presence of 5mol% CUCI2, significant alkene amination is observed, but the product consists of a complicated isomeric mixture arising from migration of the double bond into thermodynamically more stable internal positions. 

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