Lewis Acid Catalysed [4+2] Heterocycloadditions between Ketone Enol Ethers and β-Ethylenic α-Oxo Esters

Abstract

The [4+2] heterocycloaddition reaction between (E)-γ-substituted β-unsaturated α-oxo esters 1a−d and cyclic and acyclic ketone enol ethers 2a−l afforded heteroadducts 3−5 in high yields when either [Eu(fod) 3 ] or SnCl 4 were used as the catalyst. With methyl (E)-benzylidenepyruvate (1a), the two catalytic modes displayed divergent stereoselectivities. In the case of the heterocycloaddition of silyl enol ether 2h, X-ray investigations established the relative configurations of the bicyclic adducts 3h and 5h, each obtained as the major isomer with [Eu(fod) 3 ] and with SnCl 4 , respectively. These as- [a] signments provided valuable information concerning the concerted vs. nonconcerted mechanism of these acid-catalysed reactions. With methyl (E)-tert-butoxymethylenepyruvate (1d), the scope of the reaction proved to be restricted to alkyl enol ethers as the dienophiles. In this case, the stereochemical process followed a different pathway, exemplified by the X-ray structure of the adduct 4q, obtained with total stereoselectivity from 1d and 1-methoxycyclohexene (2f) when SnCl 4 was the catalyst. present a survey of these results, and Ϫ from stereochemical assignment of representative structures Ϫ to deduce a set of significant arguments concerning the concerted vs. nonconcerted mechanisms that can be ascribed to [Eu(fod) 3 ]vs. SnCl 4 -catalysed reactions.

The Asymmetric Formal Hetero‐Diels–Alder Reaction of Methyl (E)‐4‐Aryl‐2‐oxo‐3‐butenoates Catalyzed by [Sc(OTf)3/pybox] Complexes

“…A comparison of its 1 H NMR spectrum with the data reported in the literature [29] confirmed that the adduct was methyl (4S*,4aS*,8aS*)-4-phenyl-8a-trimethylsiloxy-4a,5,6,7,8,8a-hexahydro-4H-chromen-2-carboxylate (7aa) ( Table 1, entries 1, 3, 4, 6 and 7). A comparison of its 1 H NMR spectrum with the data reported in the literature [29] confirmed that the adduct was methyl (4S*,4aS*,8aS*)-4-phenyl-8a-trimethylsiloxy-4a,5,6,7,8,8a-hexahydro-4H-chromen-2-carboxylate (7aa) ( Table 1, entries 1, 3, 4, 6 and 7).…”

“…[29] If Sc III coordinates the chromen oxygen atom, a ring-opening reaction occurs with loss of the C4a proton and formation of the assumed intermediate reported in An alternative desilylating reagent is trifluoroacetic acid, which was tested on enantiomerically pure (4S,4aS,8aS)-7ba in CH 2 Cl 2 . If Sc III , acting as a Lewis acid, coordinates the TMSO oxygen atom, then epimerisation at C8a may occur and (4R,4aR,8aS)-5ba can form.…”

“…[29] The enantioselective variant of the reaction requires three steps of stereocontrol to give enantiomerically pure 7. This formal hetero-Diels-Alder reaction has been interpreted as being the result of a stepwise sequence of two reactions: a Mukaiyama-Michael addition, in which the C4-C4a bond is formed, and an intramolecular ring closure in which the Lewis acid coordinated oxygen atom of 1 attacks the carbon atom of the oxonium intermediate to give the C1-C8a bond.…”

“…[29] The third step is the intramolecular cyclization of the oxygen atom to the oxonium carbon atom of 12. Formation of the second stereocentre as (4aS) to give the Michael intermediate 12 stems from a minimization of the steric interaction that is feasible with an "anti" attack of the Re-face of 2, with the trialkylsilyloxy group removed from the congested core of complex 11.…”

“…HPLC analysis, column, eluant, experimental conditions, and retention times, as well as the IR, 1 H-, 13 C NMR, the [α] D values, and the elemental analyses are given for each specific product. [29] IR (nujol): ν = 1744 (C=O) cm -1 . Table 1, entries 1-6 were performed by following the general method described above.…”