Enantioselective Organocatalytic Direct Michael Addition of Nitroalkanes to Nitroalkenes Promoted by a Unique Bifunctional DMAP-Thiourea

Abstract

A new catalyst is designed, synthesized, and evaluated for the asymmetric Michael addition of nitroalkanes to nitroalkenes. The obdurate nature of this reaction has made this a formidable challenge to subdue by asymmetric catalysis. The catalyst design includes a thiourea function to activate the nitroalkene by a double H-bond and a 4-dimethylaminopyridine unit to deprotonate the nitroalkane and to bind the resulting nitronate anion also by a double H-bond. The chiral scaffold for the catalyst is 2,2'-diamino-1,1'-binaphthalene (BINAM), and a bis-conjugate is prepared by the attachment of the thiourea unit and the dimethylaminopyridine moiety (DMAP) via the two amino groups. The resulting catalyst will effect the reaction of nitroalkanes to a variety of nitrostyrenes and gives excellent asymmetric inductions (91-95% ee) over a range of 10 substrates. Remarkably, the asymmetric induction increases with decreasing catalyst loading with the optimal compromise between rate and induction at a loading of 2 mol %.

Enantioselective Michael Addition of Nitroalkanes to Nitroalkenes Catalyzed by Chiral Bifunctional Quinine‐Based Squaramides

“…The absolute configuration of the syn product 6 a was assigned as ( S , S ) by comparing HPLC data with that in the literature. The configurations of the remaining products were assigned by analogy …”

“…succeeded in the synthesis of 1,3‐dinitro compounds with excellent diastereoselectivity and enantioselectivity by using a chiral La(OTf) 3 / N , N′ ‐dioxide complex (OTf=trifluoromethanesulfonate) . In addition, Wulff et al. designed a bifunctional DMAP‐based thiourea derivative [DMAP=4‐( N , N ‐dimethylamino)pyridine], as Wang et al.…”

H‐Bond: Τhe Chemistry‐Biology H‐Bridge

“…Its potential as a catalyst has been relatively recently realized and appreciated in H donor organocatalysts. A broad range of this type of catalysts has been developed …”

Stimuli-responsive Cooperative Catalysts Based on Dynamic Conformational Changes toward Spatiotemporal Control of Chemical Reactions

“…A thiourea unit and a DMAP unit can cooperatively function in a bifunctional organocatalyst to promote a Michael reaction. 20 The molecular motor rotates the functional units in unidirectional fashion and changes their spatial arrangement. Irradiation of 312 nm light induces isomerization of the thermally stable trans-stilbene derivative, (P,P)-trans-8 to the cis-stilbene isomer ((M,M)-cis-8) at 20°C, in which the two functionalities are brought into close proximity ( Figure 7, step 1).…”