Asymmetric Cascade Assembly of 1,2-Diaza-1,3-dienes and α,β-Unsaturated Aldehydes via Dienamine Activation

Abstract

A cascade vinylogous 1,6-Michael addition/1,4-proton shift/aza-Michael addition/hemiaminal formation sequence of 1,2-diaza-1,3-dienes and β-substituted 2-butenals has been developed under the influence of dienamine activation of a chiral secondary amine. This method exhibits high regio- and chemoselectivity and provides an efficient and straightforward approach to bicyclic l,8-diazabicyclo[3.3.0]octane skeletons with a tetrasubstituted stereogenic center with fair to excellent enantioselectivity.

Recent Progress in Organocatalytic Asymmetric Domino Transformations

“…Very recently, Chen and co‐workers utilized 1,2‐diaza‐1,3‐dienes 55 and β‐substituted 2‐butenals 56 as the reaction partners in a domino asymmetric vinylogous 1,6‐Michael addition/1,4‐proton shift/aza‐Michael addition/hemiaminal formation reaction (Scheme ) . The dienamine catalysis using the chiral prolinol O ‐triphenylsilyl ether ( S )‐ 59 as the catalyst and 3,5‐difluoromandelic acid ( 60 ) as an acid additive (the same stereoselectivity was obtained with both chiral and racemic 60 ) provided the bicyclic l,8‐diazabicyclo[3.3.0]octane skeletons 58 in high stereo‐, regio‐ and chemoselectivities …”

Enantioselective Dearomatization of Indoles by an Azoalkene‐Enabled (3+2) Reaction: Access to Pyrroloindolines

“…Recently, azoalkenes have emerged as versatile building blocks for the construction of nitrogen‐containing structural motifs . In reported examples, these heterodienes have been used mainly as either Michael acceptors in conjugate addition reactions or as electron‐deficient heterodienes in (4+2) cyclizations . We hypothesize that azoalkenes may be suitable CCN 1,3‐dipoles because of the potential hydrazone–enamine tautomerization, thus providing a novel approach for the dearomatization of indoles and expedient synthesis of pyrroloindolines (Figure ).…”

“…[11] In reported examples,t hese heterodienes have been used mainly as either Michael acceptors in conjugate addition reactions or as electron-deficient heterodienes in (4+ +2) cyclizations. [12,13] We hypothesize that azoalkenes may be suitable CCN 1,3dipoles because of the potential hydrazone-enamine tautomerization, thus providing an ovel approach for the dearomatization of indoles and expedient synthesis of pyrroloindolines ( Figure 2). Foranasymmetric process to be in place,we envisioned that chiral phosphoric acids [14] (CPA) could provide efficient asymmetric control.…”

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

“…Scheme a shows an example of the reaction of di‐nucleophilic species 99 , which first react with dienals 93 by 1,6‐addition, followed by 1,4‐addition, with both steps activated by a chiral aminocatalyst ( Cat.12 ) . Scheme b shows the synthesis of a class of enantioenriched bicyclopyrazolidines 103 through a dienamine‐iminium cascade with β,β‐disubstituted enals 101 as reactants …”