Diels–Alder addition of the fumarate and acrylate of S-methyl lactate to α-hydroxy orthoquinodimethanes

Abstract

. 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...

The mechanism of stereoselectivity in the cycloaddition reactions of α-hydroxy-ortho-quinodimethanes with the fumarate of methyl lactate and mandelate

“…Presumably the exo cycloadduct readily closes to the lactone 14 as has been noted in similar cycloadducts (4). The endolexo ratio given in Table 1 for dienophile 11 is calculated using the ratio of the nrnr integration for the presumed endo doublet at 5.13 ppm to the sum of the other two doublets.…”

“…For all cycloadducts H1 appear between 4.6 and 5.2 ppm (in CDCl,) and endo (cis-1,2) coupling constants, J,,, are 2-5 Hz, while exo (trans-1,2) coupling constants are 7-12 Hz (for previous examples see refs. [2][3][4][5][6]17). The results of the product study are shown in Table 1.…”

“…Their ratios, measured by hplc, were 9:15:34:42 (presumed exo-si, exo-re, endo-1, and endo-2 respectively. The exo-re isomer was identified by comparison to an authentic sample (4,5). The two endo adducts were both separated and characterized, although it could not be determined -which was the erzdo-re and which was the endo-si isomer.…”

“…The organic phase was dried (Na2S04) and the solvent evaporated, leaving a viscous oil (1.51 g). The oil was chromatographed on silica (80% ethyl acetate/hexanes) to give a semicrystalline product (1 .Ol g, 54%); mp 52-53°C; ir (CH2Cl2): 1728 cm-I; 'H nrnr (300 MHz, CDCI,) 6: 6.92 (s, 2H), 4 …”

“…We recently published several accounts of the stereoselective and asymmetric Diels-Alder reactions of a-hydroxy-ortho-quinodimethanes (a-hydroxy-o-QDMs) with the fumarate of methyl lactate or methyl mandelate (1)(2)(3)(4)(5).…”