Thermal generation of alpha-hydroxy-orthoquinodimethane and reaction with the fumarate, maleate and acrylate of S-methyl lactate

Charlton, James L.; Koh, Kevin; Plourde, Guy L.

doi:10.1016/s0040-4039(00)99221-9

Cited by 24 publications

(11 citation statements)

References 10 publications

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“…11) and 1-hydroxy-1,3-dihydrobenzo[c]thiophene-2,2-dioxide (9, ref. 12), and determined the diastereoselectivity of its reaction with both the fumarate and acrylate of S-methyl lactate, 2 and 10 (5).…”

Section: Resultsmentioning

confidence: 99%

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Asymmetric synthesis of podophyllotoxin analogs

Charlton¹,

Plourde²,

Koh³

et al. 1990

Can. J. Chem.

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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...

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Section: Resultsmentioning

confidence: 99%

“…Hydroxy diacid, 5 To a solution of (S)-lactyl lactone 4 (57.6 mg, 0.15 mmol) in tert-butyl alcohol (7 mL) was added aqueous HC1 (lo%, 15 mL). The solution was heated for 3 days using a sand bath maintained at 80°C.…”

Section: Methodsmentioning

confidence: 99%

Asymmetric synthesis of podophyllotoxin analogs

Charlton¹,

Plourde²,

Koh³

et al. 1990

Can. J. Chem.

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“…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.…”

Section: Resultsmentioning

confidence: 99%

“…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.…”

Section: Resultsmentioning

confidence: 99%

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

Charlton¹,

Maddaford²

1993

Can. J. Chem.

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The Diels-Alder cycloaddition reaction of the fumarate of methyl lactate or methyl mandelate with a-hydroxy-orthoquinodimethane produces an unexpected exo product with very high asymmetric induction. Experiments and calculations have been carried out that show that the origin of the stereoselectivity in these reactions is related to hydrogen bonding between the a-hydroxy-o-quinodimethane and the lactate or mandelate group in the dienophile. La reaction de cycloaddition de Diels-Alder du fumarate du lactate de mCthyle ou du mandelate de methyle avec l'ahydroxy-ol-tho-quinodimethane conduit a un produit exo inattendu, avec une induction asymCtrique trks ClevCe. On a effectuC des experiences et des calculs qui montrent que l'origine de la stCrCosClectivitC de ces rkactions est relike a la liaison hydrogkne entre 1'a-hydroxy-ortho-quinodimethane et le groupe lactate ou mandClate du dienophile.[Traduit par la redaction]

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