Copper(I)-Catalyzed Enantioselective Incorporation of Ketones to Cyclic Hemiaminals for the Synthesis of Versatile Alkaloid Precursors

Abstract

A general catalytic enantioselective method that can produce five-, six-, and seven-membered N-heterocycles possessing various ketone moieties starting from stable and easily available cyclic hemiaminals and ketones was developed. The method involves three successive steps in one pot (aldol addition, dehydration, and enantioselective intramolecular aza-Michael reaction), all of which are promoted by a chiral copper(I)-conjugated Brønsted base catalyst. This method is useful for rapid access to versatile chiral building blocks for the synthesis of drug-lead alkaloids.

Metal‐Free Activation of C(sp3)–H Bond, and a Practical and Rapid Synthesis of Privileged 1‐Substituted 1,2,3,4‐Tetrahydroisoquinolines

“…Consequently, and given the low acidity of phenylacetylene, the alternative mechanism proposed by Kanai and co‐workers in the case of cyclic hemiaminals, does not seem a likely explanation (Scheme ). More precisely, cotarnine as a cyclic hemiaminal would exist in equilibrium with linear amino aldehyde II .…”

Synthesis, Reactivity, Functionalization, and ADMET Properties of Silicon-Containing Nitrogen Heterocycles

“…It is noteworthy that similar simple dihydroquinolones require half the reaction time and remain in cyclic form. 18 The isomers converged on the stable cyclic hemiaminal 37 in the presence of acidic methanol (Scheme 7). The hemiaminal could then react cleanly with mild nucleophiles in the presence of a Lewis acid such as BF 3 ·OEt 2 , although this could be substituted with anhydrous ZnOTf 2 with equal effect (Table 3).…”

Enolizable Carbonyls and N,O‐Acetals: A Rational Approach for Room‐Temperature Lewis Superacid‐Catalyzed Direct α‐Amidoalkylation of Ketones and Aldehydes

“…We have developed a room‐temperature catalytic direct α‐amidoalkylation of ketone donors . The reaction proceeds under remarkably mild reaction conditions under the guidance of 0.5–2 mol % of the Lewis superacid Sn(NTf 2 ) 4 as an optimal catalyst without any amino additive.…”

“…This prompted us to investigate the reaction in more detail with the aim of establishing in a more rational manner the identity of the reaction partners that are able to productively combine in this milder and more appealing room temperature variant, thereby providing a breakthrough in N ‐acyliminium ion chemistry [Scheme , Eq. (2)] …”