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.

Enantiodivergent [4+2] Cycloaddition of Dienolates by Polyfunctional Lewis Acid/Zwitterion Catalysis

“…The previously not available endo product was obtained with an ee of 98 %. Prior to this study, only the exo isomer of 11 was accessible with moderate dr by chiral amine catalysis with TONs <20 [24, 25] …”

“…Prior to this study, only the exo isomer of 11 was accessible with moderate dr by chiral amine catalysis with TONs < 20. [24,25] To learn more about the role of the aprotic betaine, experiments with several control catalysts were conducted (Table 4). Cs 2 CO 3 (2.5 mol %) in the absence of a Cu complex formed racemic product 3 aB in 95 % yield as an endo/exo mixture (84:16).…”

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, (24) 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.…”

Aminocatalytic Privileged Diversity‐Oriented Synthesis (ApDOS): An Efficient Strategy to Populate Relevant Chemical Spaces

“…Although enamine catalysis has been widely used with aldehydes as precursors, α‐enolizable α,β‐unsaturated ketones such as 46 have been also incorporated to form cross‐dienamine intermediates. Using this approach, Jørgensen et al developed a simple but important strategy for access to norcamphor derivatives in good yields and with high levels of stereocontrol (Scheme ) . Bicyclo[2.2.1]heptane scaffolds 48 are present in a large number of natural and synthetic compounds with a variety of biological activities, including antiviral, antifungal, antidiabetic, etc.…”