Claisen solvent-free

A solvent-free synthesis of benzo[b]furan derivatives 10-79, a class of compounds which is often found in physiologically active natural products, was described by Shanthan Rao and coworkers. These authors heated phosphorane 10-71 for 8 min in a microwave oven and obtained the benzo[b]furan 10-74 in 73% yield (Scheme 10.18) [25]. The sequence is initiated by an intramolecular Wittig reaction, providing alkyne 10-72 this underwent a subsequent Claisen rearrangement to give the intermediate 10-73. Also in this case, normal oil-bath heating gave much lower yields (5%) of the desired product the authors hypothesize that the micro-... 

Scheme 10.18. Solvent-free domino Wittig-Claisen cyclization-process.

Kasi SV, Raja TK (2006) A rapid microwave assisted claisen rearrangement of 4-allyloxy-2-methylquinolines under solvent free condition. Ind J Heterocycl Chem 16 195-196... 

As with ketone enolate anions (see 16-34), the use of amide bases under kinetic control conditions (strong base with a weak conjugate acid, aprotic solvents, low temperatures), allows the mixed Claisen condensation to proceed. Self-condensation of the lithium enolate with the parent ester is a problem when LDA is used as a base, ° but this is minimized with LICA (lithium isopropylcyclohexyl amide).Note that solvent-free Claisen condensation reactions have been reported. ° ... 

Yoshizawa, K., Toyota, S., Toda, F. Solvent-free Claisen and Cannizzaro reactions. Tetrahedron Lett. 2001,42, 7983-7985. 

A few solvent-free examples of Claisen rearrangement reactions under the action of microwave irradiation have been described. One involves the double Claisen rearrangement of bis(4-allyloxyphenyl)sulfone into bis(3-allyl-4-hydroxy-phenyl)sulfone (Scheme 8.43) [111]. Similarly, 3 -allyl-2 -hydroxyacetophenone has been obtained in quantitative yield from 2 -allyloxyacetophenone by Bennett et al. [112]. 

Many reports have focused on the functionalization and derivatization of cyclo-pentadienyl groups bound to iron in ferrocene complexes. As an example, a series of ferrocenyl esters have been prepared via solvent-free reactions of ferrocenoyl fluoride with substituted phenols after microwave heating for just 1 min. " In the case of 4-bromophenol, the YIF was 1.2, but most substrates gave somewhat lower yields than the conventional method. However, the microwave approach did not require the addition of A, A -dimethylaminopyridine that was necessary conventionally. Other reports include a green approach to the acylation of ferrocene using the polymeric sulfonic acid Nation as an acid catalyst " and a one-pot approach to the synthesis of l,5-dioxo-3-substituted[5]ferrocenophanes from l,T-diacetylferrocene and aldehydes via a Claisen-Schmidt reaction. " " ... 

Chalcones (123) are commonly prepared by Claisen-Schmidt or aldol condensation. An important way to synthesize chalcones (123) is the Friedel-Crafts acylation involving treatment of acid chlorides (121) with arenes (122). Such a protocol for the synthesis of chalcones (123) was developed by More et al. (2012) using nano-ZnO heterogeneous catalyst under solvent-free conditions at room temperature (Scheme 9.38). Arenes (122) of all sorts, activated as well as unactivated, reacted smoothly to afford the chalcones (123) in excellent yield. High regioselectivity was observed during the course of reaction, which occurred selectively at the para-position of OMe, Br, Me, and Cl. 

Nolan and coworkers have recently reported the gold-catalysed transformation of allqmes and allylic alcohols to homoallylic ketones. This reaction involved the hydroalkojqrlation of the allq ne followed by Claisen rearrangement. It proceeded in solvent-free conditions, at veiy low catalyst loading. Internal and terminal allq nes were successfully used as well as different allylic alcohols. The recyclability of the catalyst was studied by conducting the reaction with model substrates (diphenyalcetylene and allyl... 

Solvent-free Claisen rearrangement of bis(4-allyloxyphenyl) sulfone under micro-wave irradiation gave high yields of bis(3-allyl-4-hydroxyphenyl) sulfone in 5 min (Yamamoto et al., 2003). It takes 2-30 h under conventional heating. It is used as a color developer for a heat- or pressure sensitive recording in industry. 

The differences in the rate constant for the water reaction and the catalyzed reactions reside in the mole fraction of substrate present as near attack conformers (NACs).171 These results and knowledge of the importance of transition-state stabilization in other cases support a proposal that enzymes utilize both NAC and transition-state stabilization in the mix required for the most efficient catalysis. Using a combined QM/MM Monte Carlo/free-energy perturbation (MC/FEP) method, 82%, 57%, and 1% of chorismate conformers were found to be NAC structures (NACs) in water, methanol, and the gas phase, respectively.172 The fact that the reaction occurred faster in water than in methanol was attributed to greater stabilization of the TS in water by specific interactions with first-shell solvent molecules. The Claisen rearrangements of chorismate in water and at the active site of E. coli chorismate mutase have been compared.173 It follows that the efficiency of formation of NAC (7.8 kcal/mol) at the active site provides approximately 90% of the kinetic advantage of the enzymatic reaction as compared with the water reaction. 

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