Diels-Alder reaction 8-Phenylmenthol

Lewis acid-mediated asymmetric Diels-Alder reactions between 2H-azirines 59, bearing chiral auxiliaries, with enophiles such as 60 afforded mixtures of bicyclic aziridine-2-carboxylates 61 (Scheme 3.20) [68]. 8-Phenylmenthol appeared to be the auxiliary of choice in this reaction in terms of yield and diastereoselectivity. 

Taguchi and coworkers175 studied the Lewis acid catalyzed asymmetric Diels-Alder reactions of chiral 2-fluoroacrylic acid derivatives with isoprene and cyclopentadiene. When a chiral l,3-oxazolidin-2-one and diethylaluminum chloride were used as the chiral auxiliary and the Lewis acid catalyst, respectively, a de of 90% was observed for the reaction with isoprene. The reaction with cyclopentadiene afforded a 1 1 mixture of endo and exo isomers with de values of 95% and 96%, respectively. The endo/exo selectivity was improved by using 8-phenylmenthol as the chiral auxiliary. Thus, the reaction... 

Diels-Alder reaction Cyclopentadiene, 78 Menthol, 172 8-Phenylmenthol, 243 Ene reaction 8-Phenylmenthol, 243 Epoxidation... 

By using chiral auxiliary groups derived from phenylmenthol or camphor, Lewis acid catalyzed Diels-Alder reactions gave an easy access to enantiomerically pure carbamate alcohols38,39. For example, the enantiomerically pure cycloadduct from cyclohexadiene and chiral IV-sulfinyl carbamate could be transformed into the bicyelic carbamate with complete transfer of chirality. 

Chiral Auxiliary for Asymmetric Induction. Numerous derivatives of (—)-8-phenylmenthol have been utilized for asymmetric induction studies. These include inter- and intramolecular Diels-Alder reactions, dihydroxylations, and intramolecular ene reactions of a,p-unsaturated 8-phenylmenthol esters. These reactions usually proceed in moderate to good yield with high diastereofacial selectivity. a-Keto esters of 8-phenylmenthol (see 8-Phenylmenthyl Pyruvate) have been used for asymmetric addition to the keto group, as well as for asymmetric [2 -F 2] photoadditions and nucleophilic alkylation. Ene reactions of a-imino esters of 8-phenylmenthol with alkenes provide a direct route to a-amino acids of high optical purity. Vinyl and butadienyl ethers of 8-phenylmenthol have been prepared and the diastereofacial selectivity of nitrone and Diels-Alder cycloadditions, respectively, have been evaluated. a-Anions of 8-phenylmenthol esters also show significant diastereofacial selectivity in aldol condensations and enantiose-lective alkene formation by reaction of achiral ketones with 8-phenylmenthyl phosphonoacetate gives de up to 90%. ... 

Two groups have recently examined enantioselective A -sulfinyl dienophile Diels-Alder reactions. In one case, Whitesell et al. found that a phenylmenthol derived N-sulfinyl carbamate adds to ( , )-2,4-hexadiene under Lewis acid catalysis to afford a single diastereomer (equation 52). If the Lewis acid was omitted, a complex mixture of cycloaddition products was obtained. Attack of the diene on the N-sulBnyl dienophile as shown in the equation would rationalize the observed results. The site of Lewis acid complexation, however, is unknown. 

A highly stereoselective hetero Diels-Alder reaction of achiral N-acylimines with chiral enolethers derived from 8-phenylmenthol has been applied to the synthesis of the taxol side chain as outlined below. 

Interactive mechanism for 8-phenylmenthol in Diels-Alder reaction... 

It appeared more attractive to carry out a Diels-Alder reaction with control of both, its regio- and stereo-chemistry. In 1975, Corey published a diastereose-lective Diels-Alder reaction with the use of 8-phenylmenthol as a chiral auxiliary. The Lewis acid fulfils two tasks on the one hand, it increases the reactivity by lowering the LUMO of the dienophile [219] on the other hand, it stabilises the s-trans conformation for steric reasons. The attack of the diene on the s-cis-dienophUe would lead to the opposite absolute stereochemistry in the product. The Diels-Alder reaction occurs diastereoselectively, because the Si-facial half of the prochiral double bond is effectively shielded by 7t-stacking with the phenyl ring of the auxiliary. In this reaction, four new stereogenic centres are generated all at once. The yield of the desired diastereomer amounts to 89 %. 

The initial step in Corey s prostaglandin synthesis was a Diels-Alder reaction between a substituted cyclopentadiene and the double bond of an acrylate ester. By binding the achiral acrylate reactant to enantiomerically pure 8-phenylmenthol, Corey placed the carbon-carbon double bond of the dienophile in a chiral environment. The result was that the diene approached the carbon-carbon double bond of the acrylate preferentially from one direction. 

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