The synthetic power of pericyclic reactions has greatly increased with the emergence of catalytic variants. Indeed, catalysis in cycloadditions [1] and sigmatropic rearrangements [2] is now well established. General methods for the catalysis of electrocyclizations, however, have remained elusive, with the notable exception of the Nazarov cyclization.[3] The development of such methods would enable electrocyclizations to occur under milder conditions and create the possibility of catalytic asymmetric variants. Herein, we report the first examples of catalytic 6p electrocyclizations and provide a detailed investigation into the mechanism of these reactions.Experimental and computational studies have shown that the rate of 6p electrocyclizations can be influenced by varying the electronics of the substituents on the triene. [4][5][6][7] Electronwithdrawing groups located in the 2-position of hexatriene systems have been observed to lower their electrocyclization energy barriers, [6,7] sometimes by as much as 10 kcal mol À1 . [7,8] We envisioned exploiting this effect to catalyze 6p electrocyclizations by the coordination of a Lewis acid to a Lewis basic electron-withdrawing group located in the 2-position of a hexatriene system. This coordination should increase the electron-withdrawing effect of the substituent, thereby decreasing the electrocyclization energy barrier. We began our investigations by computationally assessing the viability of this approach in the catalysis of 6p electrocyclizations. Hexatriene systems with methyl ester substituents at all possible positions and orientations were modeled by density functional theory (Figure 1). A proton, serving as the simplest Lewis acid, was bonded to the carbonyl oxygen atom at the lone pair anti to the hexatriene.[9] As seen in Figure 1, these calculations predict a slight increase and decrease of the electrocyclization energy barrier for the (E,Z)-and (Z,Z)-1-carbomethoxy-substituted hexatriene systems (Figure 1 A and B), respectively. Calculations additionally predict a small decrease of the electrocyclization energy barrier for the 3-substituted system (Figure 1 D). However, we found that the electrocyclization energy barrier is predicted to decrease by 10 kcal mol À1 upon protonation of the 2-carbomethoxy-substituted triene system (Figure 1 C). An intrinsic reaction coordinate search in both directions from the protonated electrocyclization transition state of this system suggests that the catalyzed pathway is a concerted process, as no stationary points other than the transition state were located between the protonated triene and protonated cyclohexadiene.

[reaction: see text] The total synthesis of bicyclo[4.2.0]octane natural products elysiapyrones A and B is described.

[reaction: see text] The stereoselective cyclization of delta-hydroxy nitriles to afford N,O-acetals and the application of this reaction toward the synthesis of glycosylamines is described.

The synthetic power of pericyclic reactions has greatly increased with the emergence of catalytic variants. Indeed, catalysis in cycloadditions [1] and sigmatropic rearrangements [2] is now well established. General methods for the catalysis of electrocyclizations, however, have remained elusive, with the notable exception of the Nazarov cyclization. [3] The development of such methods would enable electrocyclizations to occur under milder conditions and create the possibility of catalytic asymmetric variants. Herein, we report the first examples of catalytic 6p electrocyclizations and provide a detailed investigation into the mechanism of these reactions.Experimental and computational studies have shown that the rate of 6p electrocyclizations can be influenced by varying the electronics of the substituents on the triene. [4][5][6][7] Electron-withdrawing groups located in the 2-position of hexatriene systems have been observed to lower their electrocyclization energy barriers, [6,7] sometimes by as much as 10 kcal mol À1 . [7,8] We envisioned exploiting this effect to catalyze 6p electrocyclizations by the coordination of a Lewis acid to a Lewis basic electron-withdrawing group located in the 2-position of a hexatriene system. This coordination should increase the electron-withdrawing effect of the substituent, thereby decreasing the electrocyclization energy barrier.We began our investigations by computationally assessing the viability of this approach in the catalysis of 6p electrocyclizations. Hexatriene systems with methyl ester substituents at all possible positions and orientations were modeled by density functional theory (Figure 1). A proton, serving as the simplest Lewis acid, was bonded to the carbonyl oxygen atom at the lone pair anti to the hexatriene. [9] As seen in Figure 1, these calculations predict a slight increase and decrease of the electrocyclization energy barrier for the (E,Z)-and (Z,Z)-1-carbomethoxy-substituted hexatriene systems (Figure 1 A and B), respectively. Calculations additionally predict a small decrease of the electrocyclization energy barrier for the 3-substituted system (Figure 1 D). However, we found that the electrocyclization energy barrier is predicted to decrease by 10 kcal mol À1 upon protonation of the 2-carbomethoxy-substituted triene system (Figure 1 C). An intrinsic reaction coordinate search in both directions from the protonated electrocyclization transition state of this system suggests that the catalyzed pathway is a concerted process, as no stationary points other than the transition state were located between the protonated triene and protonated cyclohexadiene. Figure 1. Relative electronic energies (kcal mol À1 ) of the thermal (numbers above line) and cprotonated carbonyl group (numbers below line) electrocyclization pathways computed at the B3LYP/6-31G** level of theory. 1-substituted trienes (A and B); 2-substituted triene (C); 3-substituted triene (D). [10]

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