Catalytic Enantioselective Approaches to the oxa-Pictet–Spengler Cyclization and Other 3,6-Dihydropyran-Forming Reactions

Abstract

This Short Review provides an analysis of the state-of-the-art in catalytic enantioselective oxa-Pictet–Spengler cyclizations. Also discussed are other catalytic reactions providing access to enantio­enriched isochromans and tetrahydropyrano[3,4-b]indoles. Context is provided and remaining challenges are highlighted.

The Pictet-Spengler Reaction Updates Its Habits

“…For instance, in the oxa-Pictet-Spengler cyclization, that is an oxygen variation of the P-S reaction, an aromatic alcohol component, usually a β-arylethyl alcohol, reacts with a carbonyl compound (aldehyde, ketone, or their masked derivatives) to yield polysubstituted isochromans (Scheme 88) [303,304]. Recently a minireview on the catalytic enantioselective approaches to the oxa-P-S cyclization has been published by Zhu et al [305]. On the other hand, arylamines linked to an activated aromatic nucleus, such as imidazole, might be treated with aldehydes to give imidazo-quinoxalines (n = 0) after DDQ oxidation [306] or triazabenzoazulenes (n = 1) [307] (Scheme 89).…”

Mechanism and origins of selectivity in the enantioselective oxa-Pictet–Spengler reaction: a cooperative catalytic complex from a hydrogen bond donor and chiral phosphoric acid

“…Unlike many other reactions proceeding through the oxocarbenium ion, the oxa-Pictet-Spengler reaction has been curiously resistant to enantioselective catalysis. 1,2 This reaction, which has the potential for broad applicability to pharmaceutical and material sciences, 3 has only recently been rendered enantioselective, 4 with excellent contributions from Seidel, 5,6 List, 7 and our own laboratory 8 (Fig. 1A).…”

Metallaphotoredox-Catalyzed Decarboxylative sp3–sp3 Cou-pling with Iso(thio)chroman and Tetrahydroisoquinoline Cores

“…3 Traditionally, these motifs are formed via the Pictet-Spengler (PS) reaction and variants, the oxa-Pictet-Spengler (OPS) and thia-Pictet-Spengler (TPS) reactions. A key requirement of these reactions, including recently-reported asymmetric versions of the PS [4][5][6][7][8][9][10][11][12] and OPS reactions, [13][14][15][16][17] is that the β-aryl ring of the nucleophile is electron-rich. [18][19][20] This requirement severely limits the scope of possible products that can be easily synthesized, which prompted us to seek alternatives.…”