Cyclo-isomerisation

There are rather few reactions that can be described as fully atom economical , i.e. when there are no co-products and all the atoms in the starting material(s) appear in the product(s). However, all isomerisation reactions necessarily fall into this category. The use of a transition metal to catalyse such a process with an appropriate substrate brings the possibility of effecting asymmetric isomerisation, a very efficient method to generate enantiomerically enriched products. Indeed, the asymmetric Rh-catalysed isomerisation of an allylamine to an enamine, which proceeds in over 96% ee, was scaled up a number of years ago for industrial production. The enamine product forms a multi-tonne feedstock for menthol and perfumery synthesis. In contrast, the cyclo-isomerisation of dienes, an equally atom-economical process that generates synthetically useful cyclic products, has seen relatively little development despite the reaction having been known for some 30 years. 

Scheme 12.6 Pro-catalyst-dependent regioselectivity in the Pd-catalysed cyclo-isomerisation of 1,6-dienes DCE = 1,2-dichloroethane (solvent) see the text for catalysts.

We shall consider reactions catalysed by two different types of pro-catalyst the first (type A) employs Pd-allyl cations ([Pd(a]lyl)(PCy3)]+/Et3SiH or [Pd(allyl)(MeCN)2] + ), and the second (type B) employs Pd-alkyl or chloro complexes ([(phen)Pd(Me)(MeCN)]+, where phen = phenanthroline, and [(RCN)2PdCl2]). These two types of catalysts give very different products in the cyclo-isomerisation of typical 1,6-dienes such as the diallyl-malonates (10), Scheme 12.6. Since there is known to be a clear order of thermodynamic stability 11 < 12 <13, with a difference of ca. 3-4 kcal mol 1 between successive pairs, any isomerisation of products under the reaction conditions will tend towards production of 12 and 13 from 11 and 13 from 12. Clearly, when 11 is the major product (as with pro-catalysts of type A), it must be the kinetic product (see Chapter 2 for a discussion of kinetic and thermodynamic control of product distributions). However, when 12 is generated selectively, as it is with pro-catalysts of type B, there is the possibility that this is either generated by rapid (and selective) isomerisation of 11 or generated directly from 10. 

Fig. 12.2 Evolution profiles for the cyclo-isomerisation of 10 catalysed by pro-catalysts of type A. Graph /, 5 mol% [Pd(aIlyl)(PCy3)] +/Et3SiH, DCE, 40°C. Graph //, 5 mol% [Pd(allyl)(MeCN)2]+, CHCI3, 40°C.

Scheme 12.7 Conclusions from the studies of the kinetics of the Pd-catalysed cyclo-isomerisation of 1,6-diene 10 (E = CO2R) to give 11, 12 and 13.

Scheme 12.9 Three isotopic labelling experiments to distinguish mechanisms I, II, III and IV (see Scheme 12.8) for the Pd-catalysed cyclo-isomerisation of 10 to 11 with a type A catalyst.

Compared with the previous example involving Rh-catalysed phenylation of cyclohexenone, the mechanistic investigation presented in this section involves a much less direct approach. This arises from the nature of the cyclo-isomerisation reaction, involving a single reactant and rather unstable intermediates. It is thus hard to manipulate the resting state of the catalytic cycle in order to facilitate direct study, e.g. by NMR, although Widenhoefer has... 

An example of how gold oxidation state can control the structure of the product formed has been provided recently3,10 when haloallenyl ketones were used in gold-catalysed cyclo-isomerisations to give furans (Scheme 12.2) ... 

In 2000, Hashmi reported one of the first applications of gold(m) chloride to homogeneous catalysis. In this report, several examples of intramolecular and intermolecular cyclisations involving, carbon-carbon and carbon-oxygen bond formation, were efficiently promoted by gold at room temperature and at low catalyst loading. The authors reported a cyclo-isomerisation/dimerisation of allenyl ketones and a,(3-unsaturated ketones (Scheme 16.50). This one-pot transformation was catalysed by 1 mol % of gold(m) chloride and proceeded at room temperature. 

Benzyne reacts with benzene to give a mixture of products in low yield. The original experiments 38> showed that the 1,4-cyclo-adduct (benzo-barrelene) (19), the valence-bond isomerised 1,2-cyclo-adduct (benzo-cyclo-octatetraene) (20), and the product of insertion into a carbon-hydrogen bond (biphenyl) (21), were obtained in 2,8, and 6% yields respectively. 

Tellurium sources, 22-24 Thermodynamics in cyclo-oligomerization, 185-186 butadiene insertion, 187-188 reductive elimination, 193, 194 selectivity control, 212 polysilane isomerisation, 158-160 see also Stability Thermolysis, 135, 136, 158 THF (tetrahydrofuran), 97, 150, 153 Thio-Wittig reaction, 37 Tin, 121... 

Since the addition of methylene to an olefin should be exothermic, with the evolution of about 90 kcal/mole, isomerisations of the initially formed cyclo-propanes are very likely, since they only need about 64 kcal/mole. RRKM-studies demonstrate that this isomerisation should be faster than the rearrangement of cyclopropanes 32, 33 to the pentenes 34, 35 Numerous studies of the photochemical generation in the gas phase provided conclusive evidence in favour of these findings uo.iii.iis). 

Cracking patterns for cyclo-paraffins over US-Y have recently been reported [9] where products from the conversion of methycyclohexane include C2-C6 compounds with C3 + C4 hydrocarbons as the major yields. The authors of this study have assumed that isomerisation of the initial carbenium ion is relatively facile and that a combination of hydrogen transfer, isomerisation, and beta scission generates the products. This is envisaged in Scheme 2 which uses the classification A, B, C for cracking, A, B for isomerisation f8,91 and which presumes that intramolecular hydrogen transfer is rapid [8]. 

Troe and his co-workers [27] have recently measured directly the lifetimes of excited molecules undergoing unimolecular decomposition, under essentially collision-free conditions. In these experiments, cyclo-heptatriene, 7-methylcycloheptatriene, 7,7-dimethylcycloheptatriene and 7-ethylcycloheptatriene were each excited electronically with a short pulse of laser radiation. This is followed by a rapid internal conversion to generate highly vibrationally excited, electronic ground state molecules which absorb in the ultraviolet, at longer wavelengths than the unexcited parent. Their decay (isomerisation to alkylbenzenes) was monitored directly with a continuous background source. 

The Zurich workers [51] have proposed a reaction sequence for photo-isomerisation of steroidal i,4 dienones which can account for all the major reaction products. In the cyclo-hexa-2,5-dienone (9), rearrangement of an excited triplet (probably n n ) was considered by Zimmerman [55] to... 

Greig and Thynne observed a sharp decrease in cyclo-C3Hg yield above about 186 °C, which can be attributed to the enhanced isomerisation of cyclopropyl to allyl radicals ... 

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