Vinylcyclopropane substituent effects

The substituent effects have been quantitatively addressed in the context of specific transformations, for example the vinylcyclopropane-cyclopentene rearrangement, and will be discussed in the appropriate sections. The donor/acceptor principles have been applied to thermal, heterolytic and transition metal catalyzed rearrangements and have been reviewed. These principles take into account the possible intermediate structures listed in Table 1 and are used to explain the reactivity of a particular cyclopropane system. In the discussion that follows emphasis will be given to the processes that are uniformly selective with regard to regio-, stereo- and enantio-chemical integrity of the products. 

Table 3 Substituent Effects in the Vinylcyclopropane-Cyclopentene Rearrangement...

Usually the activation free energy required for the thermal vinylcyclopropane-cyclopentene rearrangement ranges from 48 to 53kcal mor A quantitative treatment of the substituent effect has been conducted It appears that the trimethyl-... 

Sperling, D., Fabian, J. Substituent effects on the vinylcyclopropane-cyclopentene rearrangement. A theoretical study by restricted and unrestricted density functional theory. Eur. J. Org. Chem. 1999, 215-220. 

Oxgaard, J., Wiest, O. Substituent effects in the vinylcyclopropane radical cation rearrangement A computational road to a new synthetic tool. Eur. J. Org. Chem. 2003,1454-1462. 

The dominant contributor to the reactivity of vinylcyclopropanes in any radical reaction is the form (4a), the cyclopropylcarbinyl radical system. The opening of a cyclopropylcarbinyl radical to a butenyl radical is among the fastest radical processes known, with a rate constant of 1.3 x 10 sec . The various stereoelectronic effects of this rearrangement have been reviewed. - The structure of (4a), deduced from its ESR spectrum - and in agreement with calculations (STO-36 basis set), is in the bisected conformation shown, predicted to be 1.4 kcal mol more stable than its perpendicularly oriented counterpart. Above -100 C only the butenyl radical (4b) can be detected. Substituent effects do not seem to operate here when the substituents are on the cyclopropane (i.e. product stabilization). The cyclopropylcarbinyl cation and anion have structures similar to (4a), bisected conformations (5) and (6), respectively. A concise summary of solvolytic and mechanistic data for system (5) has recently appeared. Reviews of cyclopropylcarbinyl anions and carbenes are also available. ... 

Liu, P Cheong, P.H.-Y., Yu, Z.-X., Wender, P.A. and Houk, K.N. (2008) Substituent effects, reactant preorganization, and ligand exchange control the reactivity in RhI-catalyzed (5 + 2) cycloadditions between vinylcyclopropanes and alkynes. Angewandte Chemie International Edition, 47, 3939-3941. 

The relative reactivities of a number of vinylcyclopropanes towards radical (PhS) addition have been examined and indicate that the cyclopropyl group is capable of transmitting substituent effects, a conclusion supported by Raman spectroscopic data. ... 

CM of allyltrimethylsilane with homoallylic alcohols containing both anti-al-lylic and syn-allylic substituents has been reported to proceed effectively and display enhanced E selectivity [72,73], The reaction has been proposed to be a step in the synthetic route leading to vinylcyclopropanes (Eqs. 40,41). 

Aryl substitution produces a bathochromic shift on 1,4-pentadienes so that standard reaction conditions (in solution at X > 250 nm) can be applied. The reaction of equation (4) shows one of the latest examples aimed at understanding the effect of an hydroxy or alkoxy function at the 3-position on the photorearrangement.In the case of the free hydroxy group, two secondary photoproducts were observed besides the two expected vinylcyclopropanes. At variance with this observation, no secondary photoproducts were detected for the phenyldimethylsilyloxy substituent. Direct or benzophenone-sen-sitized irradiation did not cause significant variation in the reaction products. 

Several vinylcyclopropane to cyclopentene rearrangements have been reported in which a cationic substituent appears to facilitate the reaction. For example, exposure of (150 equation 23) to excess di-ethylaluminum chloride at 0 C for 12 min furnished (151), which served as a key intermediate in Corey and Myers synthesis of the plant hormone antheridogen-An. Attempts to effect this transformation thermally were unsuccessful. In a similar fashion, treatment of (152 equation 24) with boron tribromide induced VCP rearrangement of this compound at room temperature, probably via initial cleavage to the allylic carbocation (153). The reaction of the analogous vinylcyclopropane lacking a phenyl group failed to go to completion under these conditions. 

The substituents attached to the vinylcyclopropane moiety may have a drastic effect upon the reaction path. For example, a methyl placed on the cyclopropane ring cis to the vinyl group orients the reaction to a 1,5-hydrogen shift (equation 122) °. ... 

Armesto and co-workers have reported the photochemical behaviour of the vinylcyclopropane derivatives (98) under w-methoxyacetophenone sensitisation in methylene chloride as the solvent. A variety of products are formed, the nature of which is dependent upon the substituent on the cyclopropyl ring. The key intermediate is believed to be the biradical (99) that is formed following energy transfer. A study of the effect of wavelength on the outcome of the irradiation of (100) has been reported. At short wavelengths (250 and 254 nm), it is thought that the S2 state of (100) is populated and this results in the formation of the three products (101), (102) and (103) in a ratio of 6 1 1. 

Diazopropenes bearing, for example, chloro substituents on the double bond can readily be purified by short-path distillation. Subsequent vinylcyclopropanations are carried out at low temperature using copper(II) catalysts such as bis(trifluoroacetonato)copper(II), copper(II) tri-fluorosulfonate and copper(II) trifluoroacetate in the presence of a 15-60-fold excess of the alkene. The dimer of rhodium(Il) acetate (0.1 mol%, tenfold excess of alkene), however, is generally more effective, leading to higher yields in this reaction (see Houben-Weyl, Vol. El9b, Table 100). 

The alkyl substituents in 1-alkyl-l-vinyl and /rfl/7 -l-alkyl-2-vinyl-cyclo-propanes have little effect on reactivity. A cis alkyl substituent may have a profound effect for example, the energy of activation is nearly 20 kcal.mole smaller and the entropy of activation is 10 eu more negative, for isomerization of cis-1 -methyl-2-vinylcyclopropane than for typical vinylcyclopropane rearrangements. Further, the sole product of this reaction is cis-1,4-hexadiene. This and related reactions, which occur by a concerted mechanism involving 1,5-hydrogen migration, are discussed in the next section. 

The effect of substitution at the internal carbon of the allene was examined next, driven in part by the potential use of this process in the synthesis of targets bearing an angular substituent. In the presence of a catalyst system derived from 5 mol% RhCKPPhjlj and 5 mol% AgOTf in toluene at 110 °C, allene-vinylcyclopropane provides 61 in 44% yield (Eq. 66). In contrast to the cycloaddition of 54, cycloaddition of 60 produces 61 as a single diastereomer. 

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