Isomerization contrathermodynamic

Several years ago, we developed a contrathermodynamic isomerization of a- to 3-pinene via diethylmyrtenylborane obtained from a-pinene by metalation-transmetalation.11 Later, (+)-p-pinene of > 99 % ee was prepared by this method.22 Extending this work to other bicyclic monoterpenes, the isomerization of (+)-2-, (+)-3-carene, and (-)-a-thujene, was studied.13 Among bicyclic monoterpene olefins with an exocyclic double bond, 3(10)-carene is a rare compound reported only a few times in the long history of terpene chemistry, and its rotation is still controversial.23,24 Sabinene is isolated from the oil of savin, and no convenient synthesis of an optically active sabinene is known. 

On heating, alkylborons may undergo isomerization by migration of the boron to a less sterically encumbered position by a series of reversible j8-hydride elimina-tion-hydroboration steps. Displacement of the isomerized olefin may be effected by addition of a second olefin, which forms a more stable alkylboron than the one displaced. This reaction has been used to effect the contrathermodynamic isomerization of olefins. 

A further example is the contrathermodynamic isomerization of e.w-3,6,6-trimethylbicy-clo[3.1.1]heptan-2-one to the eWo-isomer. The e.vo-isomer is first converted to the enamine. Kinetically controlled protonation furnishes the e.vo-salt which isomerizes quantitatively to the endo-isomer on standing. Final hydrolysis then gives the endo-ketone 2132. 

Figure 6.1. (a) Contrathermodynamic isomerization of a trisub-stituted alkene to a disubstituted one. (b) Thermodynamically favored isomerization of an allylic amine to an enamine. 

This process is synthetically important because a sacrificial alkene such as 1-decene or 1-hexadecene can be added to bias the overall reaction toward a specific target alkene. Mechanistically, thermal isomerization apparently involves a series of reversible elimination reactions of borane followed by re-addition in an anti-Markovnikov manner.2 If the sacrificial alkene has a significantly higher boiling point, then the desired alkene can he distilled from the reaction medium.22a xhe sacrificial alkene must not boil < 160°C, however, which is the temperature required for borane isomerization. This process makes it possible to isomerize the double bond of an alkene to a less substituted isomer, a process that Brown termed contrathermodynamic isomerization.29,30 methylenecyclohexane (41) was prepared from 1-methylcyclohexene by... 

A rapid acid-catalyzed contrathermodynamic isomerization of the 2-phenylseleno-l,3-selenanes 43 has been reported (Equation 4) <1996TL8015>. 

The formation of isomeric aldehydes is caused by cobalt organic intermediates, which are formed by the reaction of the olefin with the cobalt carbonyl catalyst. These cobalt organic compounds isomerize rapidly into a mixture of isomer position cobalt organic compounds. The primary cobalt organic compound, carrying a terminal fixed metal atom, is thermodynamically more stable than the isomeric internal secondary cobalt organic compounds. Due to the less steric hindrance of the terminal isomers their further reaction in the catalytic cycle is favored. Therefore in the hydroformylation of an olefin the unbranched aldehyde is the main reaction product, independent of the position of the double bond in the olefinic educt ( contrathermodynamic olefin isomerization) [49]. 

An important and frequently observed phenomenon in alkene pyrolysis is the ready equilibration of E and Z isomers at FVP temperatures above 500 °C. The apparently contrathermodynamic conversion of the E into the Z isomer has been quantified over the range 500-900 °C for stilbene, cinnamyl alcohol and cinnamonitrile37. In the last case, the proportion of Z isomer increases to 38% at 900 °C. In certain cases the diradical implicit in the isomerization process can be trapped by an intramolecular reaction and this is exemplified by the formation of 2-phenylindane in low yield from FVP of 56 at 700 °C37. The cis cyclobutene diester 58 is assumed to be formed as an intermediate in the FVP of the bicyclic sulphone 57 at 775 °C by loss of SO2 and ethylene. Under these conditions, however, it reacts further to give equal proportions of the E diesters 59... 

Selective isomerization of the ( )-alkene to (Z)-alkene has also been carried out via infrared multiphoton excitation [70]. Upon IR laser irradiation at MOOO/cm of 2-butene 19a and 2-pentene 19b, essentially quantitative contrathermodynamic conversion (i>to-Z) can be achieved (Sch. 9). It is concluded that small differences in cross-section may be amplified in the multiphoton up-pumping process. However, the quantum yield was too small to measure (<10-6). 

The influence of adjacent stereogenic centers on the diastereoselectivity of the cyclization is addressed in entries 4 13. Alkyl or aryl substituents in the homoallylic position lead only to a moderate preference for the 4,6-m-product (Table 14, entries 4 7)9. Surprisingly, the triflu-oromethyl group exerts complete stereocontrol, which is attributed to its steric and additional electronic repulsion of the enolate moiety in the cyclization transition state (for a detailed discussion see the preceding section). The intramolecular reactions of the bissulfone derivatives (Table 14, entries 11 -14)19 feature a contrathermodynamic production of mainly civ-substituted vinylcyclopentanes. Epimerization of the zr-allyl complex is faster than cyclization, so that an equilibrium between the different isomeric zwitterions is established. Due to unfavorable steric interactions with the substituent R, palladium is preferentially located irunx to R in the cyclization transition state favoring the m-product. The use of toluene, tetrahydrofuran, and acetonitrile as solvents results in poorer diastereoselectivities. Some restrictions apply to the kind of nucleophile employed, thus 2-oxo esters may only give the 0-alkylated product (cf. Table 12)2 19-20. 

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