Electrophilic addition, selectivity between alkenes

From the point of view of both synthetic and mechanistic interest, much attention has been focused on the addition reaction between carbenes and alkenes to give cyclopropanes. Characterization of the reactivity of substituted carbenes in addition reactions has emphasized stereochemistry and selectivity. The reactivities of singlet and triplet states are expected to be different. The triplet state is a diradical, and would be expected to exhibit a selectivity similar to free radicals and other species with unpaired electrons. The singlet state, with its unfilled p orbital, should be electrophilic and exhibit reactivity patterns similar to other electrophiles. Moreover, a triplet addition... 

The course of addition reactions of ROH-XeF2 to alkenes has been elucidated using norbomene, 2-methylpent-2-ene and hex-l-ene as model substrates. It turned out that the alkoxyxenon fluoride intermediates (ROXeF) can react either as oxygen electrophiles (initially adding alkoxy substituent) or as apparent fluorine electrophiles (initially adding fluorine), depending on the reaction conditions. Simple addition of poorly nucleophilic alcohols to norbomene was also observed in certain instances. Selectivity between the various reaction pathways (simple fluorination, alkoxyfluorina-tion, or alcohol addition) proved to be sensitive to various reactions conditions, especially solvent, temperature, and catalyst.27... 

Unlike the carbohydrates with double bonds at positions other than between C-1 and C-2 ( isolated alkenes ), which exhibit normal alkene chemistry, glycals are vinyl ethers and therefore undergo a number of highly selective addition reactions due to the strongly polarized double bonds and the presence of bulky substituents at the C-3 allylic centers. Straightforward addition reaction includes initial electrophilic addition at the double bond, followed by the addition of a nucleophile at C-1 to give the 1,2-trans adduct (O Scheme 19). 

The N+ relationship, as discussed above, is a systematization of experimental facts. The equation of Scheme 7-4 has been applied to nearly 800 rate constants of over 30 electrophiles with about 80 anionic, neutral, and even cationic nucleophiles covering a range of measured rate constants between 10-8 and 109s 1 (Ritchie, 1978). Only about a dozen rate constants deviated from the predicted values by more than a factor of 10, and about fifty by factors in the range 5-10. It is therefore, very likely that this correlation is not purely accidental. Other workers have shown it to be valid for other systems, e.g., for ferrocenyl-stabilized cations (Bunton et al., 1980), for coordinated cyclic 7r-hydrocarbons (Alovosus and Sweigart, 1985), and for selectivities of diarylcarbenes towards alkenes (Mayr, 1990 Mayr et al., 1990). On the other hand, McClelland et al. (1986) found that the N+ relationship is not applicable to additions of less stable triphenylmethyl cations. 

Cyclopropane formation occurs from reactions between diazo compounds and alkenes, catalyzed by a wide variety of transition-metal compounds [7-9], that involve the addition of a carbene entity to a C-C double bond. This transformation is stereospecific and generally occurs with electron-rich alkenes, including substituted olefins, dienes, and vinyl ethers, but not a,(J-unsaturated carbonyl compounds or nitriles [23,24], Relative reactivities portray a highly electrophilic intermediate and an early transition state for cyclopropanation reactions [15,25], accounting in part for the relative difficulty in controlling selectivity. For intermolecular reactions, the formation of geometrical isomers, regioisomers from reactions with dienes, and enantiomers must all be taken into account. 

Because systematic variations in selectivity with reactivity are commonly quite mild for reactions of carbocations with n-nucleophiles, and practically absent for 71-nucleophiles or hydride donors, many nucleophiles can be characterized by constant N and s values. These are valuable in correlating and predicting reactivities toward benzhydryl cations, a wide structural variety of other electrophiles and, to a good approximation, substrates reacting by an Sn2 mechanism. There are certainly failures in extending these relationships to too wide a variation of carbocation and nucleophile structures, but there is a sufficient framework of regular behavior for the influence of additional factors such as steric effects to be rationally examined as deviations from the norm. Thus comparisons between benzhydryl and trityl cations reveal quite different steric effects for reactions with hydroxylic solvents and alkenes, or even with different halide ions... 

In the second example, the electrophile is an anhydride with two reactive carbonyl groups tha nearly but not quite the same. This is a recipe for bad selectivity - reaction will occur at carbonyls. In addition, stereoselectivity will not be so good as the alkenes are trisubstituted there is not as much difference in stability between cis and trans as there was in the disubstitc enal. 

It is often difficult to make a comparison between the various results obtained for the same polyenes as different reaction conditions (ratio of reactants, temperature, time) were used in each case. The addition of dichlorocarbene (chloroform/base/phase-transfer catalysis) to straight chain and cyclic unconjugated di- and trienes, carried out under identical conditions but varying the catalysts, showed the peculiar properties of tetramethylammonium chloride. Under precisely tailored conditions, either highly selective mono- or polyaddition of dichlorocarbene to the polyenes is possible tetramethylammonium chloride was the most efficient catalyst for monocyclopropanation. (For the unusual properties of tetramethylammonium salts on the phase-transfer catalyzed reaction of chloroform with electrophilic alkenes see Section 1.2.1.4.2.1.8.2. and likewise for the reaction of bromoform with allylic halides, see Section 1.2.1.4.3.1.5.1.). For example, cyclopropanation of 2 with various phase-transfer catalysts to give mixtures of 3, 4, and 5, ° of 6 to give 7 and 8, ° and of 9 to give 10 and 11. °... 

The first syntheses of dendralenes by C2-C3 bond formation (Scheme 1.25) were reported by Tsuge and coworkers in 1985 and 1986, and proceed via substitution at either a bromide 160 or an epoxide 163, followed by elimination (Scheme 1.26) [116, 117]. Similar addition/elimination sequences to carbonyl groups or epoxides [120], and substitution reactions [121], followed. Such methods have been superseded by cross-coupling techniques that take place between a 2-functionalized 1,3-butadiene and an alkene (each can be either electrophilic or nucleophilic) or a 4-functionalized 1,2-butadiene and alkene, and occur with allylic transposition (Scheme 1.25). No doubt due to the ready availability of alkenyl halides and allenes, and the variety of increasingly mild and selective reaction variants, cross-coupling has provided access to a large number of diversely substituted dendralenes over the past 20 years, some of which have even been part of natural product syntheses [14,122,123]. 

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