Asymmetric Diels−Alder Reactions of a New Enantiomerically Pure Sulfinylquinone:  A Straightforward Access to Functionalized Wieland−Miescher Ketone Analogues with (R) Absolute Configuration

Abstract

An efficient and highly stereocontrolled preparation, on a large scale, of two new Wieland−Miescher-type diketones is described. The approach centers on a diastereoselective Diels−Alder reaction using a new enantiomerically pure sulfinylquinone. Mechanistic investigations of this cycloaddition on several dienes are described.

Enantioselective Access to Key Intermediates for Salvinorin A and Analogues

“…The following known compounds were isolated as pure samples and showed data matching those of reported compounds: (S)-2, [16] 3, [15] (Ϯ)-7b, [19a] 8a and 8b, [14] 9b. [31] General Procedure for ZnBr 2 -Catalyzed Diels-Alder Reactions: To a solution of freshly prepared sulfinylquinone (S)-2 (0.75-1.00 mmol, 1 equiv.)…”

“…By analogy with our previous study, [16] we anticipated that precomplexation of the sulfinylquinone 2 with ZnBr 2 would be necessary to obtain good conversion in reasonable time. Thus, by mixing (S S )-sulfinylquinone 2 with 2 equiv.…”

“…We have already demonstrated that (S S )-6-methoxy-2-(p-tolylsulfinyl)-3-methyl-1,4-benzoquinone (2) is a very efficient building block for the construction of functionalized decalins with an angular methyl group, and we have disclosed a new access to Wieland-Miescher diketone analogues. [16] (S S )-Sulfinylquinone 2 was prepared on large scale within 10 days from methylhydroquione.…”

“…[16] The decomposition observed when cycloadduct 6 was warmed to room temperature (Scheme 2) was attributed to a reaction between the sulfenic acid (p-TolSOH) -resulting from the syn-elimination of the sulfoxide moiety -and the newly formed cycloadduct 4. Classical sulfenic acid scavengers (Michael acceptors, PPh 3 ) failed to trap p-TolSOH.…”

Synthesis and Biological Evaluation of ABCD Ring Fragments of the Kibdelones

“…To access hydroxystyrene 9, commercially available bromovanillin 13 was demethylated with AlCl 3 in pyridine and selectively methylated with Li 2 CO 3 and MeI in DMF [8] which was followed by silyl protection to afford aldehyde 14 (55 % yield, 3 steps). Dakin oxidation of 14 with m-CPBA, [9] followed by hydrolysis of the intermediate formate, provided a phenol intermediate which was directly subjected to Stille coupling with vinyl tributylstannane to afford hydroxystyrene 9 (63 %, 3 steps). [10] Unfortunately, attempted thermal and catalyzed DielsAlder cycloaddition of quinone 12 and hydroxystyrene 9 were unsuccessful, largely due to instability and decomposition of the quinone 12.…”