Two analogs of podophyllotoxin, with the same absolute stereochemistry as the natural product, have been synthesized from the cycloadduct between a-hydroxy-a'-phenyl-o-quinodirnethane and the furnarate of S-methyl lactate. After initial attempts to produce the cycloadduct from photochemically generated a-hydroxy-a'-phenyl-o-quinodirnethane failed, a study of the thermal generation and reaction of a-hydroxy-o-quinodirnethane with the fumarate and acrylate of S-methyl lactate was made. A comparison was made of the diastereoselectivity of these cycloaddition reactions to those previously reported, in which the o-quinodirnethane was generated photochemically. The a-hydroxy-o-quinodirnethane was produced both by the known thermolysis of benzocyclobutenol and by therrnolysis of l-hydroxy-l,3-dihydrobenzo[c]thiophene-2,2-dioxide. The diastereorneric excess for the cycloaddition reactions was found to be greater than 95% with modest (ca. 55%) isolated yields of the major cycloadducts. Following these model studies, it was found that a-hydroxy-a'-phenyl-o-quinodirnethane produced thermally from l-hydroxy-3-phenyl-1,3-dihydrobenzo[c]thiophene-2,2-dioxide could be added to the furnarate of S-methyl lactate with high diastereoselectivity and good yield. The product of this reaction was converted to the podophyllotoxin analogs 7 and 17. Utilisant le cycloadduit obtenu par condensation de I'a-hydroxy-a'-phtnyl-o-quinodirnkthane et du fumarate du lactate de S-rnCthyle, on a synthCtisC deux analogues de la podophyllotoxine possCdant la m&rne stCrCochirnie que le produit naturel. I1 n'a pas Ct C possible de produire le cycloadduit B partir de l'a-hydroxy-a'-phenyl-o-quinodimkthane obtenu photochirniquernent; on a donc utilist une rnkthode thermique pour gCnCrer I'a-hydroxy-o-quinodirnCthane et pour rCaliser sa rCaction avec le furnarate du lactate de S-rnCthyle. On a effectuk une cornparaison de la diastkrCosClectivitC de ces rCactions de cycloaddition avec celles rapportCes antkrieurernent, alors que 1'0-quinodirnethane avait CtC gCnerC d'une f a~o n photochirnique. L'-a-hydroxy-oquinodirnkthane a CtC obtenu par la thermolyse connue du benzocyclobutCno1 ainsi que par la therrnolyse du 1-hydroxy-1,3-dihydrobenzo[c]thiophkne-2,2-dioxyde. On a trouvC que l'excks de diastCrCornkres eit plus grand que 95% alors que le rendernent en cycloadduits principaux isolCs n'est que de 55%. A la suite de ces Ctudes rnodkles, on a trouvC que I 'a-hydroxy-a'-phCnyl-o-quinodirnkthane obtenu therrniquernent B partir du l-hydroxy-3-phCnyl-l,3-dihydrobenzo[c]thiophkne-2,2-dioxyde peut &tre addition& au furnarate du lactate de S-rnkthyle avec une excellente diasterkosklectivitC et un excellent rendernent. Le produit de cette rkaction peut &tre transform6 dans les analogues 7 et 17 de la podophyllotoxine.Mots clis : o-quinodirnkthanes, asyrnetrique, Diels-Alder, lactate, podophyllotoxine, lignane.[Traduit par la revue] Introduction The synthesis of aryl tetralin ligans such as dimethyl isolariciresinol or podophyllotoxin requires the stereoselective a...

. 67, 574 (1989).The cycloaddition of a-hydroxy orthoquinodimethane, generated photochemically from 2-methylbenzaldehyde, to the fumarate and acrylate of S-methyl lactate has been found to give a single diastereomer with high asymmetric induction (>95% de). This reaction provides a new and versatile synthetic route to substituted tetralins of high optical purity. A trans stereochemistry between the vicinal hydroxyl and carboxylactyl groups has been established for these cycloadducts. This is in contrast to previous work where cis stereochemistry has always been found for major cycloadducts of a-hydroxy o-QDMs. The high asymmetric induction, unusual diastereoselectivity, and the potential use of these reactions in asymmetric synthesis are discussed. On a observC que la cycloaddition de l'a-hydroxy orthoquinodimCthane, obtenu d'une f a~o n photochimique a partir du mCthyl-2 benzaldkhyde, sur le fumarate et sur l'acrylate du lactate de S-mCthyle conduit a un seul diastCriorntre avec une induction asymktrique Clevte (>95% de). Cette rCaction s'avkre &re une route de synthese nouvelle et versatile vers les tetralines substitubes de puretk optique ClevCe. On a Ctabli que les groupements hydroxyle et carboxylactyle vicinaux de ces cycloadduits sont de stCrCochimie trans. Ce rtsultat est en opposition avec ceux obtenus au cours de travaux antCrieurs alors qu'on a toujours obtenu une stCrCochimie cis pour les cycloadduits principaux des a-hydroxy o-QDM. On discute de I'induction asymktrique tlevte, de la diastCrCostlectivitC inhabituelle et des usages possibles de ces reactions en syntheses asymCtriques.Mots cle's : o-quinodimkthanes, Diels-Alder, asymCtrique, cycloaddition, induction, diastCrCosClective.[Traduit par la revue] Introduction Developing strategies towards the synthesis of enantiomerically pure compounds is one of the goals of modem organic chemistry and the study of asymmetric Diels-Alder reactions exemplifies the pursuit of this goal (1-5). The corresponding study of asymmetric Diels-Alder reactions of orthoquinodimethanes (0-QDMs) has received much less attention although o-QDMs have been extensively utilized as intermediates in non-asymmetric syntheses of chiral molecules (6). The addition of asymmetric control to the cycloaddition reactions of o-QDMs would provide a route to a large number of optically active compounds of interest. While a few examples of the intermolecular addition of chiral o-QDMs to achiral dienophiles have been published (6-9), only one example of a chiral dienophile reacting with an achiral o-QDM has been published (10). A possible reason for the lack of reports of asymmetric DielsAlder reactions of o-QDMs is that high diastereoselectivity in such reactions is often achieved only in the presence of Lewis acid catalysts. Such catalysts are frequently incompatible with the conditions required to generate the transitory and very reactive o-QDMs.Because of our interest in the use of o-QDMs in synthesis we have searched the literature to find chiral dienophiles that give high diastereo...

An asymmetric synthesis of 2-amino-6,7-dimethoxy -1,2,3,4-tetrahydronaphthalene, which can be converted to the title compound by a literature procedure, is described. The synthesis, starting from 2-amino-4,5-dimethoxybenzoic acid and the acrylate of S-methyl lactate, was accomplished in eight steps in 11% overall yield and >97% optical purity.Key words: o-quinodimethanes, Diels-Alder, asymmetric, cycloaddition, induction, diastereoselective, ADTN. Chem. 68, 2028Chem. 68, (1990. On dCcrit une synthkse asymktrique du 2-amino-6,7-dimCthoxy-1,2,3,4-tCtrahydronaphtalkne qui peut Ctre transforme dans le composC mentionnC dans le titre par une procedure dCcrite dans la 1ittCrature. La synthkse, i partir de I'acide 2-amino-4,5-dimCthoxybenzoique et de I'acrylate du lactate de S-mCthyle, a CtC rCalisCe en huit Ctapes, avec un rendement global de 11% et une pureti optique >97%.

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Optically active -hydroxy acids and esters are important and versatile building blocks in organic synthesis.1 Various methods have been developed for their preparation. These methods include the reduction of a-oxo esters2•3 and asymmetric oxygenation of chiral imide enolates.4 Very recently Corey and Link demonstrated that reduction of -trichloromethyl ketones by catecholborane in the presence of chiral oxazaborolidine catalyst yielded optically active trichloromethyl carbinols which on treatment with 4-methoxyphenoxide afforded optically active -aryloxy acids. Treatment of the methyl esters of the -aryloxy acids with ceric ammonium nitrate (CAN) furnished the desired -hydroxy esters.5The methodology reported in this paper for the preparation of optically active -hydroxy acids and a-aryloxy acids make use of the recently discovered reaction of (R)pantolactone esters of racemic -halo carboxylic acids with amines which furnished predominantly one of the two possible diastereomeric -amino esters with diastereoselectivity ranging from 88:12 to >95: <5 and in yields up to 80%.6 The greater than 50% yield of one diastereomer is due to epimerization of the slower reacting (2S)--halo ester into the faster reacting (2ñ)-isomer by the halide generated in the displacement reaction or added to the reaction mixture.