A Catalytic Asymmetric Reaction Involving Enolizable Anhydrides

Abstract

In the presence of a highly efficient novel bifunctional organocatalyst at low loadings under mild conditions, enolizable homophthalic anhydrides can be added to a range of aromatic and aliphatic aldehydes to give dihydroisocoumarins, with excellent yields and diastereo- and enantiocontrol (up to 99% ee).

Direct Aerobic Oxidative Reactions of 2‐Hydroxyacetophenones

“…Encouraged by this outcome, we planned to perform reactions of 2‐hydroxyacetophenone with other compounds under these conditions. Initially, homophthalic anhydride was chosen as the reaction partner, because so far no reports of its reaction with phenylglyoxal are available, though a reaction with benzaldehyde was recently published . Given that homophthalic anhydride needed to be activated with a base, we screened a variety of bases for the reaction (Table ).…”

“…Initially, homophthalic anhydride was chosen as the reaction partner, because so far no reports of its reaction with phenylglyoxal are available, though a reaction with benzaldehyde was recently published. [15] Given that homophthalic anhydride needed to be activated with a base, we screened a variety of bases for the reaction (Table 1). Although there was no conversion with potassium carbonate, 1,8diazabicyclo [5.4.0]undec-7-ene (DBU) indeed provided 20 % yield of the biologically important phthalide [16] 4a (Table 1, Entry 2), the structure of which was unambiguously confirmed by X-ray crystallography.…”

Catalytic Asymmetric Tamura Cycloadditions

“…The Michael acceptor 17 was reacted with a range of enolizable anhydrides 1 and 25-30 in the presence of 24 at 30 8C ( Table 2). These reactions represent the first examples of the expansion of enantioselective cycloadditions involving enolizable anhydrides beyond either homophthalic- [10] or a-aryl succinic [11] analogues. The brominated analogue 31 was formed with comparable efficacy and stereocontrol (entry 2).…”

“…We have recently [10] shown that the bifunctional organocatalyst 9 can promote the formal cycloaddition of benzaldehyde (8) to 1 to afford the substituted dihydroisocoumarin lactone 10 with excellent yield, and enantio-and diastereocontrol (Figure 1 D). [11] We had posited that 9 both catalyzes the tautomeric equilibrium between 1 and 2 c and organizes the encounter between 2 c and the squaramide-bound 8 by general acid-base catalysis.…”

“…In preliminary experiments, the N-Boc oxindole 17 was reacted with the stable and the readily handled homophthalic anhydride (1) in the presence of squaramide 9 (the previously identified optimum catalyst for the cycloaddition of aldehydes with 1 [10] ) in MTBE at 30 8C (entry 1, Table 1). [15a] Under these reaction conditions, the Tamura cycloaddition proceeded to full conversion, thus producing the tetracyclic spiroadduct 18 with excellent diastereo-and enantiocontrol.…”