Alkene substitution

Table 12.8. Relative Rates of Radical Addition as a Function of Alkene Substitution"...

Fig. 8.16 The different approaches of an alkene substituted with an electron-donating group (EDG) to nitroethene...

The Michael addition of nih oalkanes to alkenes substituted with two elecbon-withdrawing groups at the a- and 3-positions provides a new method for the preparation of functionalized alkenes. Although reactions are not new, Ballini and coworkers have used this sbategy in the synthesis of polyfunctionalized unsaturated carbonyl derivatives by Michael addition of nih oalkanes to enediones as shown in Eqs. 7.124-7.126. Success of this type of reaction depends on the base and solvent. They have found that DBU in acetonihile is the method of choice for this puipose. This base-solvent system has been used widely in Michael additions of nitroalkanes to elechon-deficient alkenes (see Section 4.3, which discusses the Michael addition). ... 

The metathesis of acyclic alkenes substituted with other hydrocarbon groups, such as cycloalkyl, cycloalkenyl, or aryl groups, has also been observed. For instance, styrene is converted into ethene and 1,2-diphenyl-ethene (stilbene) (9, 9a). 

The alkene substituted with the electron accepting group has the LUMO (it ) lowered by the interaction with the vacant orbital of the substituent. The high-lying SOMO interacts with the LUMO of the alkene more effectively than with the HOMO. The interaction is the symmetry-allowed it - n interaction (Scheme 30a). The configuration of the alkene is retained. 

Scheme 30a,b [2 + 2] Cycloaddition reactions of excited carbonyl compounds with the alkenes substituted by electron-accepting (a) and -donating (b) groups... 

The reaction gives better yield with dienes, styrenes, or alkenes substituted with EWGs than with simple alkenes. These groups increase the rate of capture of the aryl radical. The standard conditions for the Meerwein arylation employ aqueous solutions of diazonium ions. Conditions for in situ diazotization by f-butyl nitrite in the presence of CuCl2 and acrylonitrile or styrene are also effective.115... 

Most recently new applications for substrate-controlled branched-selective hydroformylation of alkenes substituted with inductively electron-with drawing substituents have emerged. A recent example is the hydroformylation of acrylamide with a standard rhodium/triphenylphosphine catalyst, which yields the branched aldehyde exclusively (Scheme 4) [40]. Reduction of the aldehyde function furnishes 3-hydroxy-2-methylpropionamide, which is an intermediate en route to methyl methacrylate. 

Scheme 32 Dependence of enyne cyclizations on alkene substitution...

In the nineteen sixties, there was some confusion about the value of p, the reaction constant for polar effects of alkyl groups on bromination rates, as calculated according to Taft s equation, log (k/k0) = p a. For 22 alkenes substituted by one, two or three linear alkyl groups, there is a satisfactory relation (16) between their reactivities, log k, in methanol and the sum of their... 

A variety of functionalities, tether lengths, and alkene substitution patterns were tolerated (Equation (35)).52,53 Of particular significance is the synthesis of a-methylene-y-butyrolactone 55, as only Zhang had reported successfully using Alder-ene chemistry to gain access to this novel system (see Section 10.12.4.3). The reaction was sensitive to the length of the tether, since there was a marked decrease in yield for the formation of the six- and seven-membered carbocycles (53 and 54, respectively) compared to the five-membered case 52. 

As the steric bulk of the propargylic substituents increased, the preference for the formation of the seven-membered ring increased as well. Formation of a ruthenacyclopentene intermediate with sterically hindered substrates involves a large amount of A(1,3) strain, leading to preferential formation of a 7r-allyl species. This novel cycloisomerization process is very sensitive to alkene substitution the requirement for a m-methyl group was evidenced by the failure of 70 to give... 

For each case we will also present catalytic analogues, namely (1) the activation of methane to form methanol with platinum, the reaction of certain aromatics with palladium to give alkene-substituted aromatics, and (2) the alkylation of aromatics with ruthenium catalysts, and the borylation of alkanes and arenes with a variety of metal complexes. 

The reaction is versatile and proceeds with a variety of cyclic and acylic alkenes substituted with alkyl, aryl, vinyl and heteroatom substituents. Allene derivatives also undergo cycloaddition with nitrones ". A variety of cyclic and acyclic aliphatic nitrones bearing aliphatic and aromatic substituents has been tested. The reaction is, however, relatively sensitive to steric constraints and proceeds easily only for mono- and disubstituted alkenes. Steric requirements for a nitrone molecule are similar and, although several reactions with R, R2 are known, good yield has been achieved only with R = H (equation 105). 

A very useful class of chiral auxiliaries has been developed for alkenes substituted with a heteroatom. These auxiliaries, attached to the heteroatom, allow for the preparation of enantiomerically enriched cyclopropanols, cyclopropylamines and cyclopropylboronic acids. Tai and coworkers have developed a method to efficiently generate substituted cyclopropanol derivatives using the cyclopropanation of a chiral enol ether (equation 78) . The reaction proceeds with very high diastereocontrol with five- to eight-membered ring sizes as well as with acyclic enol ethers. The potential problem with the latter is the control of the double bond geometry upon enol ether formation. A detailed mechanistic study involving two zinc centers in the transition structure has been reported. ... 

Alkenes substituted by capto-dative groups such as 5 and 7 undergo cyclodimerization under milder conditions. Mixtures of head-to-head stereoisomers are also obtained in these cases.5,6... 

Ketene acetals and thioacetals can be used as ketene equivalents in cyclobutanone synthesis in situations where ketene to alkene cycloadditions are inefficient such as in the case of electron-deficient alkenes.14 Although thermal cycloadditions of ketene acetals and thioacetals with electron-deficient alkenes have been observed (see Section 1,3.2.1.), such cycloadditions proceed more efficiently and under milder conditions with metal catalysts. Efficient cycloadditions between ketene dimethyl acetal and alkenes substituted by a single electron-withdrawing group have been reported.15... 

Chiral cyclobutanes can be prepared by cycloaddition of alkenes substituted with one or more chiral auxiliary groups. A diastereofacial selectivity of 95% was observed in the diethylalu-minum chloride catalyzed cycloaddition of 1,1-dimethoxyethene (36) with ( — )-dimenlhyl-3-yl fumarate (37).16 The chiral cyclobutane 38 has been used as an intermediate in the synthesis of carbocyclic oxetanocin analogs. 

Alkenes substituted with potential leaving groups are masked alkynes and are thus useful alternative dipolarophiles. They react with diazo compounds, producing pyrazolines, which can undergo elimination to give 3//-pyrazoIes. 

Reductive coupling of alkenes and l -dienes. In the presence of Hg(OAc), or Hg(OAc), HgO (I 1) and NaBH(OCH,), 1,3-dienes undergo reductive coupling in methanol with alkenes substituted with election-withdrawing groups (CN, CCXX H, ( C)C ll 1) to form the methyl ether of allyl alcohols. ... 

Support-bound alkenes substituted with at least one electron-withdrawing group can react with primary or secondary amines (Table 10.6). If acrylates are used as Michael acceptors, the products (fl-alanine derivatives) are generally stable and do not undergo [l-elimination either upon N-acylation or upon treatment with TFA (for a longer synthetic sequence with a support-bound 2-(l-piperazinyl)propionate, see [42]). Suitable solvents for the addition of amines to electron-poor alkenes are THF, NMP, and DMSO. DMF is less suitable because it often contains dimethylamine, which also adds to Michael acceptors [112],... 

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