Alkene derivatives intermolecular mechanisms

The unexpected formation of cyclopenta[b]indole 3-339 and cyclohepta[b]indole derivatives has been observed by Bennasar and coworkers when a mixture of 2-in-dolylselenoester 3-333 and different alkene acceptors (e. g., 3-335) was subjected to nonreductive radical conditions (hexabutylditin, benzene, irradiation or TTMSS, AIBN) [132]. The process can be explained by considering the initial formation of acyl radical 3-334, which carries out an intermolecular radical addition onto the alkene 3-335, generating intermediate 3-336 (Scheme 3.81). Subsequent 5-erafo-trig cyclization leads to the formation of indoline radical 3-337, which finally is oxidized via an unknown mechanism (the involvement of AIBN with 3-338 as intermediate is proposed) to give the indole derivative 3-339. 

The mechanism of Scheme 5 accounts for these observations. Both excited diazirine 29 and carbene 20 are regarded as product precursors. A strict partition is postulated, whereby cyclobutene 30 comes only from 29, while the carbene reacts only intermolecularly, either with the freon solvent or added alkene. In Scheme 5, the excited diazirine pathway is expanded by interposition of the opened diazirine biradical, 29, as the proximate partitioning intermediate.46-48 Of course either an excited diazirine or a diazirine-derived biradical, would satisfy the need for a second intermediate in cases where curved correlation of addn/rearr vs. [alkene] require expansion of the kinetic scheme. 

Kinetics is used to investigate mechanisms of radical additions to alkenes. Outside the solvent cage, the initiator-derived radicals may undergo the desired bimolecular reaction with the substrate, or side reactions. When the substrate is an alkene, the exothermic intermolecular addition of the reactive radical (R ) to the double bond results in the formation of two new single carbon-carbon bonds in place of the double bond. This reaction represents conversion of an initiator into a propagating radical in radical polymerisations, and is becoming increasingly important in a number of synthetically useful intermolecular small molecule reactions. The addition of R to monosubstituted and 1,1-disubstituted alkenes is nearly always at the unsubstituted carbon atom (tail addition), and thus is normally not affected by the individual steric demand of the alkene substituents. Equation 10.4 is the expression for the rate of addition (R ) of R to an alkene where [M] is the monomeric alkene concentration ... 

The palladium-catalyzed reaction of allyl chloride 11 with the benzyne precursor 104 to produces phenanthrene derivatives 131 is also known [83]. A plausible mechanism for this intermolecular benzyne-benzyne-alkene insertion reaction is shown in Scheme 38. Initially n-allyl palladium chloride la is formed from Pd(0) and 11. Benzyne 106, which is generated from the reaction of CsF and 104, inserted into la to afford the aryl palladium intermediate 132. A second benzyne insertion into 132 produce 133 and subsequent carbopalladation to the alkene afford the cyclized intermediate 134. f>- Iydride elimination from 134 followed by isomerization gave 9-methylphenanthrene 131. 

In contrast to the preferred meta mode of intramolecular photoaddition of 5-phenyl-l-pentenes, where the alkene and benzene groups are separated by three atoms, irradiation of the styrene (64) yields a single stereoisomer of the ortho adduct (65). In (64), not only are the reacting units separated by 4 atoms, but also it is the styrene rather than the benzene which is excited. Comparable photoreactivity is seen for phenanthrene-styrene systems such as (66) which yield 2+2 adducts (67) along with products derived from competing Paterno-Btichi reaction of the ester carbonyl with the alkene side chain. The photochemical cycloaddition also proceeds in an intermolecular fashion between the ester of 9-phenanthrene carboxylic acid and para-methoxy-0-methylstyrene. The mechanism of this reaction is shown to involve addition of the styrene to the singlet excited state of the phenanthrene derivative. °... 

General discussion of intra- and intermolecular interactions 3 van der Waals interactions 3 Coulombic interactions 5 Medium effects on conformational equilibria 5 Quantum mechanical interpretations of intramolecular interactions 7 Methods of study 8 Introduction 8 Nmr and esr spectroscopy 8 Microwave spectroscopy (MW) 12 Gas-phase electron diffraction (ED) 12 X-ray crystallographic methods 13 Circular-dichroism spectroscopy and optical rotation 14 Infrared and Raman spectroscopy 18 Supersonic molecular jet technique 20 Ultrasonic relaxation 22 Dipole moments and Kerr constants 22 Molecular mechanic calculations 23 Quantum mechanical calculations 25 Conformations with respect to rotation about sp —sp bonds 27 Carbon-carbon and carbon-silicon bonds 28 Carbon-nitrogen and carbon-phosphorus bonds 42 Carbon-oxygen and carbon-sulphur bonds 48 Conformations with respect to rotation about sp —sp bonds Alkenes and carbonyl derivatives 53 Aromatic and heteroaromatic compounds 60 Amides, thioamides and analogues 75 Conclusions 83 References 84... 

Three different approaches to the synthesis of five-membered cyclic ureas have recently been described that involve Pd-catalyzed alkene diamination reactions. In a series of very interesting papers, Muniz has described the conversion of alkenes bearing pendant ureas to imidizolidin-2-one derivatives using catalytic amounts of Pd(OAc)2 in the presence of an oxidant such as PhI(OAc)2 or CuBr2 [61, 62]. For example, these conditions were used to effect the cyclization of 79 to 80 in 78% yield (Eq. (1.34)) [62aj. These reactions proceed via a mechanism similar to that shown above in Eq. (1.33), except that the heteropalladation may occur in a syn- rather than anti- fashion, and the reductive elimination occurs with intramolecular formation of a C—N bond rather than intermolecular formation of a C—O bond. The alkene diamination reactions have also been employed for the synthesis of bisindolines (Eq. (1.35)) [63] and bicyclic guanidines (Eq. (1-36)) [64]. 

In 2004, Wolfe et al. used a carboamination reaction for the first time for the stereoselective synthesis of substituted pyrrolidine derivatives via a Pd-catalyzed intermolecular iV-arylation followed by intramolecular cyclization reaction sequences. The reaction proceeds via an innersphere mechanism with the formation of the Pd(Ar)(NRR ) complex. In this reaction, a -(A-arylamino) alkene was treated with an aryl or heteroaryl bromide in the presence of NaO Bu as the base and Pd catalyst the corresponding 2,3- or 2,5-disubstituted pyrrolidine derivatives (Scheme 40.4) were obtained in good yields and excellent diastereoselectivity. ... 

The mechanism of intermolecular Au(I)-catalysed cyclopropanation of alkenes with 1,6-enynes, leading to biscyclopropylated derivatives (64) in a highly stereospecific manner, has been explored experimentally and theoretically. The results are consistent with the participation of cyclopropyl gold carbene species (65) as a key intermediate. 

A review of recent developments in 1,3-dipolar cycloaddition of nitrones with sila-, thia-, phospha-, and halo-substituted alkenes has been reported. A DFT study of solvent effects on the intermolecular 3-l-2-cycloaddition reaction of norbornadiene with 3,4-dihydroisoquinoline A(-oxide at 398.15 K indicated that the reaction proceeds via a synchronous concerted mechanism. Chiral imidazolidinone salts, in the absence of water, promote the 1,3-dipolar cycloaddition reaction of alanine-derived ketonitrones... 

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