Organocatalytic Enantioselective Higher‐Order Cycloadditions of In Situ Generated Amino Isobenzofulvenes

Abstract

The [8+2] cycloaddition of indene‐2‐carbaldehydes and nitro olefins is described to provide benzonorbornene scaffolds in a highly peri‐, diastereo‐, and enantioselective fashion in the presence of a C2‐symmetric aminocatalyst. This reaction, which proceeds through a transient semi‐aromatic amino isobenzofulvene, represents the first example of catalytic formation and transformation of these species. Quantum chemical calculations suggest a kinetically controlled stepwise mechanism where the stereochemistry is determined in the first bond‐forming event. Beyond the useful [8+2] cycloadducts, [10+4] cycloadducts have been identified in silico as potential off‐pathway intermediates.

Enantioselective Synthesis of Tropane Scaffolds by an Organocatalyzed 1,3‐Dipolar Cycloaddition of 3‐Oxidopyridinium Betaines and Dienamines

“…[20b,25b] However, a concerted rearrangement TS from Int-IIa-(5 + 4) to Int-IIa-(5 + 2) could not be located (see Supporting Information), but formation of Int-IIa-(5 + 2) from Int-IIa-(5 + 4) via Int-Ia can be mechanistically classified as a stepwise Cope rearrangement. [36] As similarly reported by Harmata and Krenske, [20b] a furan forming (3 + 2) pathway can be accessed after a larger dihedral rotation around the newly formed bond in Int-Ia. This pathway has an associated activation energy of 8.2 kcal mol À 1 for TS-IIa-(3 + 2) to form the endergonic product Int-IIIa-(3 + 2) (ΔG = 2.4 kcal mol À 1 ) after hydrolysis of the catalyst.…”

“…As reported by Harmata, Krenske, and Burns, direct interconversion between (5+4) and (5+2) cycloadducts may also be possible via a Cope rearrangement [20b,25b] . However, a concerted rearrangement TS from Int‐IIa‐(5+4) to Int‐IIa‐(5+2) could not be located (see Supporting Information), but formation of Int‐IIa‐(5+2) from Int‐IIa‐(5+4) via Int‐Ia can be mechanistically classified as a stepwise Cope rearrangement [36] …”

Palladium‐Catalyzed Asymmetric [4+3] Cycloadditions of Indene‐2‐carbaldehydes with 4‐Vinylbenzoxazinanones Toward Polycyclic 5H‐Benzo[b]azepines

“…Indene‐2‐carbaldehydes are fundamental cyclic polyene building blocks for organic synthesis [12] . Because indene‐2‐carbaldehyde is a versatile substrate for a variety of 8π‐ and 10π‐electron components higher‐order cycloadditions, [13] we were curious about how it would behave when confronted with vinyl benzoxazinanones. On the basis of our previous work, [14] we envisaged the application of chiral phosphines in Pd(0)‐catalyzed [4+3] cycloadditions of 4‐vinyl benzoxazinanones and indene‐2‐carbaldehydes for the enantioselective construction of 5 H ‐benzo[ b ]azepines (Scheme 1c).…”

The Game of Electrons: Organocatalytic Higher‐Order Cycloadditions Involving Fulvene‐ and Tropone‐Derived Systems

“…This concept wasi ndependently elaborated by Jørgensen and co-workers,w ho proposed the use of indene-2-carbaldehydes 13 as ahigherene precursors and presented the first catalytic formation of amino isobenzofulvene systems and transformationo ft hese species via higher-order cycloaddition with olefins 14 (Scheme8). [17] Structurally related, achiral amino isobenzofulvenes were previously reported to participate in [10+ +2]-cycloadditions with N-phenylmaleimide. [18] In Jørgensen's report, the reactionw as performed in presence of a C 2 -symmetric aminocatalyst 4b to provide highly peri-, diastereo-, and enantioselective formation of chiral benzonorbornene scaffolds 15.T he aldehyde moietyi nt he originally formed products was reduced in ao ne-pot manner with NaBH 4 to provide more stable alcohols 15 and to ease the isolation.…”