Stereoselective Synthesis of Heterocyclic Cage Compounds by Domino Conjugate Additions

Abstract

Heterocyclic cage compounds have been stereoselectively synthesized from enantiopure [(S)R]-[(p-tolylsulfinyl)methyl]-p-quinols or their amine analogues and 2-(trimethylsilyloxy)furan in the presence of Bu4NF. The method is particularly valuable not only because of the stereochemical control but also because the reactions occur in an experimentally simple one-pot procedure through a domino sequence of three consecutive conjugate additions. The intermediate 1,4-adducts could be isolated when the reaction was carried out in the presence of BF3 x OEt2.

Recent developments in chiral non-racemic sulfinyl group chemistry in asymmetric synthesis

“…152 Whereas unsubstituted quinols afford a 1:1 mixture of diastereoisomers, a methyl substituent on the double bond enables a complete diastereoselection. The resulting adducts were desulfinylated to produce enantiomerically pure cage compounds.…”

Stereoselective Trimerization of [(S)R]-[(p-Tolylsulfinyl)methyl]-p-quinols and p-Quinamines

“…We demonstrated that they are able to act as both acceptor and donor in successive conjugate additions. 8,9 Having in mind the reported biomimetic approaches to bisorbicillinoids and the interest of finding enantiopure and stable analogues of quinols, which could be used as substrates in biomimetic synthesis, we decided to explore if sulfinyl (1) Evidence supporting the real intermediacy of quinols in such biosynthetic routes has been recently reported: Abe, N.; Sugimoto, O.; Tanji, K.; Hirota, A. Jautelat, R.; Vassilikogiannakis, G.; Baran, P. S.; Simonsen, K. B. Chem. Eur.…”

“…We demonstrated that they are able to act as both acceptor and donor in successive conjugate additions. 8,9 Having in mind the reported biomimetic approaches to bisorbicillinoids and the interest of finding enantiopure and stable analogues of quinols, which could be used as substrates in biomimetic synthesis, we decided to explore if sulfinyl p-quinol 1 and p-quinamine 2 could behave like the natural quinol metabolites in a dimerization process. It is known that free ortho-quinols, which are extremely reactive, dimerize instantaneously, 10 but there is not evidence of such behavior in p-quinols.…”

“…The low yield obtained suggested a significant role of the sulfoxide in the process. This result is in accordance with our previous studies related to 1,4-conjugate additions on both 4-sulfinylmethyl p-quinols 6a,b and p-quinamines, 8 where we demonstrated that the presence of the sulfoxide significantly increased the electrophilicity of the cyclohexadienone moiety.…”

“…Interest of these reactions in the biomimetic enantioselective synthesis of natural products is evident since differently substituted p-quinols and pquinamines, as well as the 4-hydroxy-4-p-(tolylsulfinyl)-methyl-2-cyclohexenones, are easily accessible in enantiomerically pure form. 6,8,9 …”