Mechanism and Origins of Enantioselectivities in Spirobiindane-Based Hypervalent Iodine(III)-Induced Asymmetric Dearomatizing Spirolactonizations

Abstract

The work of Kita et al. on asymmetric oxidative dearomatization of naphthol carboxylic acids to spirolactones mediated/catalyzed by a novel, conformationally rigid μ-oxo-bridged hypervalent iodine­(III) species is a landmark discovery in enantio­selective iodine­(III) catalysis [Kita, Y.; et al. Angew. Chem., Int. Ed. 2008, 47, 3787. DOI: 10.1002/anie.200800464; J. Am. Chem. Soc. 2013, 135, 4558. DOI: 10.1021/ja401074u]. We have investigated the detailed mechanism of this important transformation using density functional theory. Calculations revealed that proton transfer from the pendant carboxylic acid of naphthols to the bridging oxygen atom or the ligand of iodine­(III) species, which enhances the nucleophilicity of the carboxylic oxygen and the nucleofugality of the iodoarene, is crucial for the dearomatizing spirolactonization. Halogen bonding between the resulting carboxylate and the electron-deficient iodine­(III) center further stabilizes the dearomatizing spirolactonization transition states. Calculations also revealed a long-neglected cleaved μ-oxo iodine­(III) species that is more reactive but less selective than the μ-oxo-bridged hypervalent iodine­(III) species itself for the oxidative dearomatization of naphthols. The coexistence of two sequential dearomatizing spirolactonization processes in the reaction system results in a lower enantio­selectivity. A new stereochemical model that is able to reproduce and rationalize the observed apparent enantio­selectivities is proposed.

Mechanism of Iodine(III)‐Promoted Oxidative Dearomatizing Hydroxylation of Phenols: Evidence for a Radical‐Chain Pathway

“…This, due to the strongly electron‐withdrawing nature of the hypervalent iodine, primes the attack of the nucleophile on the ring (pathway 1; TS1 ), resulting in simultaneous dearomatization and reduction of iodine. Such a mechanism has been supported by the recent computational study by Houk and Xue on the asymmetric spirolactonization, wherein it has been shown to proceed via a feasible energy barrier (≈21 kcal mol −1 ) and to reproduce the experimentally observed enantioselectivity . In the second mechanistic pathway, often referred to as dissociative, intermediate A undergoes a unimolecular fragmentation, reducing iodine and yielding phenoxenium ion B (pathway 2; TS2 ).…”

“…In particular, the substantial rate enhancement with the increaseo fw ater content speaks strongly against the dissociative mechanism (Scheme 2, pathway 2), in which H 2 Oi se ngaged only after the rate-determining dissociation of intermediate A.T his is furtherr einforced by the large negative entropyo f activation,u nlikely for ad issociative process.T he measured experimental free energy barrier (22-23 kcal mol À1 )i sa lso considerably lower than that determined computationally for pathway 2( > 28 kcal mol À1 ), [7] but in agreement to those computed for pathways 1a nd 3( 21-24 kcal mol À1 ). [6,9] However,t he computational studies on the associativem echanisms have shown that in both the transition states of type TS1 and TS3 (Scheme 2, pathways 1a nd 3) for the barriers to be feasible, the attack of nucleophile must proceed with as imultaneous deprotonation by an acetate anion (not shown in the scheme). [6,9] This is, however,inconsistent with the lack of asolvent kinetic isotope effect upon the exchange of H 2 Of or D 2 O. Overall,t he data allows with high confidence to discard the pathways shown in Scheme 2a st he correct reactionm echanisms.…”

“…[6,9] However,t he computational studies on the associativem echanisms have shown that in both the transition states of type TS1 and TS3 (Scheme 2, pathways 1a nd 3) for the barriers to be feasible, the attack of nucleophile must proceed with as imultaneous deprotonation by an acetate anion (not shown in the scheme). [6,9] This is, however,inconsistent with the lack of asolvent kinetic isotope effect upon the exchange of H 2 Of or D 2 O. Overall,t he data allows with high confidence to discard the pathways shown in Scheme 2a st he correct reactionm echanisms.…”

“…Such am echanism has been supported by the recent computational study by Houk and Xue on the asymmetric spirolactonization, wherein it has been shown to proceed via a feasible energy barrier(% 21 kcal mol À1 )a nd to reproduce the experimentally observed enantioselectivity. [6] In the second mechanistic pathway,o ften referred to as dissociative, intermediate A undergoes au nimolecular fragmentation, reducing iodine and yielding phenoxenium ion B (pathway 2; TS2). The latter subsequently reacts with the nucleophile to afford the dearomatized product.…”

Natural and Synthetic Spirobutenolides and Spirobutyrolactones

“…Later, they reported that the slight modification in catalyst backbone enhanced the enantioselectivity of the dearomatizing‐spirolactonization of naphthols . Recently, Houk and coworkers studied a thorough mechanism of this significant protocol by density functional theory (DFT) . In this study, it was found that the proton transfer occurred from the tethered acid of naphthols to the linking oxygen atom or the ligand of iodine(III).…”