Direct Access to Multifunctionalized Norcamphor Scaffolds by Asymmetric Organocatalytic Diels–Alder Reactions

Abstract

A general organocatalytic cross‐dienamine activation strategy to produce chiral multifunctionalized norcamphor compounds having a large diversity in substitution pattern is presented. The strategy is based on a Diels–Alder reaction of an amino‐activated cyclopentenone reacting with most common classes of electron‐deficient olefins, such as nitro‐, ester‐, amide‐, and cyano‐substituted olefins, chalcones, conjugated malononitriles, CF3‐substituted enones, and fumarates. The corresponding norcamphor derivatives are formed in good yield, excellent enantioselectivities, and with complete diastereoselectivity. Furthermore, it is demonstrated that quaternary stereocenters and spiro norcamphor compounds can be formed with high stereoselectivity. The present development provides a simple, direct, and efficient approach for the preparation of important norcamphor scaffolds.

Synthesis of Simplified Azasordarin Analogs as Potential Antifungal Agents

“…The endo/exo diastereoselectivity could also be modified by using suitable Lewis acids. The second approach uses as the key step an asymmetric organocatalytic Diels-Alder reaction reported by Jørgensen, 19 which could also provide highly enantiomerically-enriched products via the catalytic enamine intermediate 7. This approach would also have the advantage of avoiding the need to preactivate the diene component via silylenol ether formation.…”

“…In order to achieve an endo-selective Diels-Alder reaction and avoid the acid sensitivity of diene 14, we examined the organocatalytic asymmetric Diels-Alder reaction reported by Jørgensen 19 The quinidine-derived amine catalyst 25 worked smoothly with cyclopentenone (Table 2, entry 1), as was reported. However, we weren't able to extend the scope to include 4-substituted cyclopentenones (entries 2, 3).…”

A theoretical study of an electronically mismatched Diels–Alder cycloaddition

“…6,7 Therefore, it is common to apply [4 + 2] cycloaddition in the drug synthesis, such as those of the chalconoid natural products and the pre-nylavonoid D-A natural products. [8][9][10][11][12][13][14][15] Generally, the classic D-A cycloadditions are reacted by electronic-decient diene and electronic-rich dienophile synergetically. [16][17][18][19] However, there are a series of untraditional D-A reactions [20][21][22][23][24][25][26][27][28][29][30][31] between electronically mismatched components, such as the addition between 1,3-butadiene and ethylene (both electron-decient components) or trans-1,3-butadiene and C60 or C70 (both electron-rich components).…”

Gold(I)‐Catalyzed Cycloisomerization of 3‐Alkoxyl‐1,6‐diynes: A Facile Access to Bicyclo[2.2.1]hept‐5‐en‐2‐ones

“…[2] One of the most commonly employed strategies relies on [4+2] Diels-Alder cycloadditions with their particular efficiency. [2,3] However, high regioselectivity remains problematic in complex unsymmetrical reagents. Efficient and rapid routes for the assembly of bicyclo [2.2.1]heptanes will be beneficial for synthesis.…”