Intermolecular reactions alkene termination

Radical species derived from reduction of ketones are also trapped by alkenes in an intermolecular reaction. Reaction only occurs with terminal alkenes of the type... 

Blechert et al. succeeded in intermolecular CM of terminal alkyne and terminal alkene. A reaction carried out in CH2CI2 at RT in the presence of 5-7mol% Ic gives a mixture of ( )- and (Z)-isomers (Table 2). Because of the nonselective stereochemical course, a silyl-protected ally alcohol is employed and the resulting metathesis product is deprotected and oxidized to afford the desired diene having an -configuration (Equation (13)). 

The reaction is thought to proceed by co-ordination of the alkene with the organopalladium(II) species, followed by carbopalladation. Subsequent p-hydride elimination regenerates an alkene and releases palladium(II). This is reduced (reductive elimination) to palladium(O) in the presence of a base, to allow further oxidative addition and continuation of the cycle (1.211). The carbopalladation and p-hydride elimination steps occur syn selectively. Excellent regioselectivity, even for intermolecular reactions, is often observed, with the palladium normally adding to the internal position of terminal alkenes (except when the alkene substituent is electron-rich as in enamines or enol derivatives), thereby leading to linear substitution products. 

A new intermolecular gold(I)-catalyzed reaction of terminal alkynes with functionalized alkenes led to 8-oxabicyclo[3.2.1]oct-3-enes by a [2 + 2 + 2] cycloaddition process in which two C—C bonds and one C—O... 

The intennolecular acylpalladation corresponds to the addition of an acyl-palladium bond onto a rr-bond system of another molecule this elementary step can also be referred to as an insertion (Scheme I). This produces another organopalladium complex, which can in principle participate in subsequent propagation or termination reactions. This excludes processes that involve alkoxycarbonylation (R— = R O—) and hydrocarbonyla-tion (R— = H—). This section will focus on nonpolymeric intermolecular reactions of acylpalladium complexes with different 7r-bond systems (alkenes, imines, dienes, and alkynes). 

Scheme 10.2 gives some examples of ene and carbonyl-ene reactions. Entries 1 and 2 are thermal ene reactions. Entries 3 to 7 are intermolecular ene and carbonyl-ene reactions involving Lewis acid catalysts. Entry 3 is interesting in that it exhibits a significant preference for the terminal double bond. Entry 4 demonstrates the reactivity of methyl propynoate as an enophile. Nonterminal alkenes tend to give cyclobutenes with this reagent combination. The reaction in Entry 5 uses an acetal as the reactant, with an oxonium ion being the electrophilic intermediate. 

An interesting antibody-catalyzed intermolecular asymmetric 1,3-dipolar cycloaddition reaction between 4-acetamidobenzonitrile N-oxide and N,N-dimethylacrylamide generating the corresponding 5-acylisoxazoline was observed (216). Reversed regioselectivity of nitrile oxide cycloaddition to a terminal alkene was reported in the reaction of 4-A rt-butylbenzonitrile oxide with 6A-acrylamido-6A-deoxy-p-cyclodextrin in aqueous solution, leading to the formation of the 4-substituted isoxazoline, in contrast to the predominance of the 5-substituted regioisomer from reactions of monosubstituted alkenes (217). 

The above intramolecular diene cyclizations are likely to proceed through a similar set of reactions as shown in Scheme 6.2 for the intermolecular variants. Thus, as depicted in Scheme 6.6, formation of the zirconacyclopropane at the less hindered terminal alkene (—> ii), generation of the tricyclic intermediate iii, Zr—Mg exchange through the intermediacy of zirconate iy and 3-H abstraction and Mg alkoxide elimination in v may lead to the formation of the observed product. Additional kinetic and mechanistic studies are required before a more detailed hypothesis can be put forward. 

Since enol silyl ethers are readily accessible by a number of methods in a regioselective manner and since the trialkylsilyl moiety as a potential cationic leaving group facilitates the termination of a cyclization sequence, unsaturated 1-trialkylsilyloxy-1-alkenes represent very promising substrates for radical-cation cyclization reactions. Several methods have been reported on the synthesis of 1,4-diketones by intermolecular oxidative coupling of enol silyl ethers with Cu(II) [76, 77], Ce(IV) [78], Pb(IV) [79], Ag(I) [80] V(V) [81] or iodosoben-zene/BFa-etherate [82] as oxidants without further oxidation of the products. 

The alkenyl iodide or triflate 369 reacts in the absence of Cul with two moles of terminal alkyne 370 to form the substituted fulvene 371. The reaction can be explained by the intermolecular insertion of the alkyne twice, followed by the intramolecular insertion of the alkene, and / -elimination to form the fulvene 371(268]. 

Macro carbocyclic rings can be constructed by cyclization of nitrile oxides derived from oj-nitro-l-al-kenes (Scheme 22). If the intervening bridge is not longer than seven atoms, only fused bicyclic products are obtained. Thus, the nitrile oxide derived from nitro compound (75a) is cyclized in 44% yield to the 5,9-fused bicyclic isoxazoline (76a).38 10-Nitro-l-decene (75b) also cyclized to (76b) in unspecified yield.39 It should be noted that these results go counter to the usual regiochemistry of an intermolecular nitrile oxide cycloaddition where the five-substituted isoxazoline is usually,27 although not always,40 heavily preferred from reaction of a terminal alkene. Thus, geometric constraints have won out over the normal electronic control. 

Another useful reaction for the difunctionalization of olefins involves a group transfer carbonylation starting from a a-(phenylseleno)carbonyl (or related derivatives) and a terminal alkene under 80 atm of CO. An alkyl radical is first formed by the photocleavage of a C-SePh bond. The addition of this radical to the olefin, followed by the incorporation of CO and radical coupling with PhSe-, gave substituted selenoesters via a three-component coupling reaction [74], The intermolecular formation of C—C bonds via phenylseleno group transfer has been likewise adopted in the reaction between ester-substituted O,Se-acetals and an olefin [75],... 

Until recently, intermolecular enyne metathesis received scant attention. Competing CM homodimerisation of the alkene, alkyne metathesis and polymerisation were issues of concern which hampered the development of the enyne CM reaction. The first report of a selective ruthenium-catalysed enyne CM reaction came from our laboratories [106]. Reaction of various terminal alkynes 61 with terminal olefins 62 gave 1,3-substituted diene products 63 in good-to-excellent yields (Scheme 18). It is interesting that in these and all enyne CM reactions subsequently reported, terminal alkynes are more reactive than internal analogues, and 1,2-substituted diene products are never formed thus, in terms of reactivity and selectivity enyne CM is the antithesis of enyne RCM. The mechanism of enyne CM is not well understood. It would appear that initial attack is at the alkyne however, one report has demonstrated initial attack at the alkene (substrate-dependent) is also possible, see Ref. [107]. 

---