Alkene, -trisubstituted, formation

Many examples of insertions of internal alkynes are known. Internal alkynes react with aryl halides in the presence of formate to afford the trisubstituted alkenes[271,272]. In the reaction of the terminal alkyne 388 with two molecules of iodobenzene. the first step is the formation of the phenylacetylene 389. Then the internal alkyne bond, thus produced, inserts into the phenyl-Pd bond to give 390. Finally, hydrogenolysis with formic acid yields the trisubstituted alkene 391(273,274], This sequence of reactions is a good preparative method for trisubstituted alkenes from terminal alkynes. 

The initial step of olefin formation is a nucleophilic addition of the negatively polarized ylide carbon center (see the resonance structure 1 above) to the carbonyl carbon center of an aldehyde or ketone. A betain 8 is thus formed, which can cyclize to give the oxaphosphetane 9 as an intermediate. The latter decomposes to yield a trisubstituted phosphine oxide 4—e.g. triphenylphosphine oxide (with R = Ph) and an alkene 3. The driving force for that reaction is the formation of the strong double bond between phosphorus and oxygen ... 

Based on information accrued during the stereochemical elucidation, macrolactone 85 was identified as a viable synthetic intermediate (Scheme 12). The authors were cognizant of the potential challenges that could arise. First, the required formation of a trisubstituted alkene in a projected Horner-Emmons macrocyclization was without strong precedent. Also, this strategy would necessitate a stereoselective reduction of the Cl5 ketone, which was predicted to be feasible based on MM2 calculations. 

These catalysts were shown to have some generality beyond trisubstituted alke-nes. In particular, Z-menthyl diazoacetate leads to moderately selective cyclopropane formation with a number of alkenes. These are illustrated in Table I. 

A great deal of work has been focused on whether the ene reaction proceeds through a concerted or a stepwise mechanism. The initially proposed synchronous pathway was challenged by a biradical , zwitterionic or a perepoxide intermediate. Kinetic isotope effects in the photooxygenation of tetrasubstituted, trisubstituted and cis-disubstituted alkenes supported the irreversible formation of an intermediate perepoxide,... 

The intermolecular kinetic isotope effect for the competition of 20 with its deuteriated analogue 22 in chloroform was negligible (Scheme 10, h/ d = 1-00 0.02). Like in other trisubstituted alkenes, this result was interpreted in terms of irreversible formation of a perepoxide intermediate. 

However, the barrier to rotation does not always predict the regioselectivity of the ene reaction of O2 with alkenes. As shown latef, it is the non-bonded interactions in the isomeric transition states that control product formation and barriers to rotation are rather irrelevant. The calculated rotational barrier values, with the HF-STO-3G method, for the allylic methyls in a series of trisubstituted alkenes, as well as the experimentally observed ene regioselectivity of a series of selective substrates, are shown in Table 9. ... 

A negligible intermolecular isotope effect of %/ d = 1.03 0.02 indicated that also for trisubstituted alkenes, formation of a perepoxide-type transition state is the ratedetermining step. 

An alternative procedure for decomposing ozonides from di- or trisubstituted alkenes is to treat them with methanol (CH3OH). The use of this reagent results in the formation of an aldehyde or ketone and a carboxylic acid ... 

Of the available trisubstituted alkenes for which we have data, only three are homologous 2-methyl-2-butene, -pentene and -hexene. Three literature enthalpy-of-formation values16,21,32 for the C5H10 compound are well within the error bars and so we have used an average (—41.4 2.0 kJ mol-1). A plot of equation 4a clearly shows the enthalpy of formation for C1112 derived from Reference 26 to be the best value. 

The formation of peracids as the effective oxidizing species has often been proposed for oxidations with sodium percarbonate in the presence of organic acids or acid anhydrides30-32. It was observed that at room temperature and in dichloromethane as solvent, the addition of acetic anhydride induced the epoxidation by sodium perborate of mono-, di- and trisubstituted alkenes, including a,/i-unsaturated ketones in a slightly exothermic reaction33 (equation 6). 

There has been extensive research into electrophilic additions to 3-substituted-l,4-dihydropyridines, such as N-methyl-3-cyano-l,4-dihydropyridine 138, which readily undergoes addition across the more reactive enamine-like 5,6-alkene to give 2,3,5-trisubstituted-l,2,3,4-tetrahydropyridines (Scheme 38) <1998JOC2728, 2000CEJ1763, 2003TL8449>. In an unusual example, the reaction with sulfinyl chlorides and triethylamine results in the formation of the 1,4-dihydropyridine sulfoxide 139, where in the absence of an additional nucleophile, the iminium intermediate is deprotonated to yield the monosubstituted 1,4-dihydropyridine product 139. 

Overman has suggested a cyclic six-membered transition state 10 for the reaction [8]. The experimental result for the formation of substituted alkenes is similar to that observed for other [3,3]-sigmatropic rearrangements. Furthermore, the preferred formation of the trans-isomer of the di- and trisubstituted alkenes is consistent with transition state 10. The activation parameters for the [3,3]-sigmatropic rearrangements are similar to related rearrangement reactions. 

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