Three‐Component Multi‐Catalytic Enantioselective Oxa‐Michael/Aldolization Sequence and Application to (+)‐Yashabushitriol Synthesis

Abstract

By a selective three-component multi-catalytic sequence, amino-catalyzed oxa-Michael addition of oximes to α,-unsaturated aldehydes has been combined with a coppercatalyzed decarboxylative aldolization. This one-pot procedure enables the rapid construction of functionalized ketodiol scaffolds in 85 to 94% ee. Simple reduction of both the resulting Polyketides are ubiquitous in natural products and drugs with unique properties resulting from their ability to form selective hydrogen-bonding frameworks (Figure 1). [1] Therefore, the discovery of efficient and selective methods for the preparation of such complex organic scaffolds has exalted scientific curiosity for decades. [2] However, despite the considerable progress observed in catalytic enantioselective synthesis notably through [a

Copper Catalyzed Decarboxylative Functionalization of Ketoacids

“…[27] Once again, we hypothesized that, upon suitable multicatalytic activation, decarboxylative aldolization using ketoacids could unlock the access to other highly useful nonsymmetric polyols (Scheme 16). [28] Among the numerous catalysts tested for the aldolization step, Cu(i-BuCOO) 2 provided the best efficiency and the adducts of the multicomponent assembly could be isolated in 48-67 % yield.…”

Development of Multi‐Catalytic Strategies Based on the Combination between Iron‐/Copper‐ and Organo‐Catalysis

“…Using (Cu(i-butyrate)2) as simple copper catalyst, [13] the aldehydes 9 formed using cat2 were efficiently transformed in the presence of keto-acids 8 to the aldolization products 10 (Scheme 3). [14] Secondary amine Cat2 efficiently controlled the formation of the first stereogenic center through iminium activation. Use of the copper complex for the decarboxylative aldolization avoided any racemization and the final aldol products were isolated in 85 to 94 % ee albeit with moderate diastereocontrol.…”

Cinchona‐Based Hydrogen‐Bond Donor Organocatalyst Metal Complexes: Asymmetric Catalysis and Structure Determination

“…[36][37][38][39][40][41][42][43][44][45] This way, multicomponent or multistep reactions could take place that cannot be realized without their combined application. [46][47][48][49][50][51][52][53][54][55][56][57] Consequently, based on our previous work, procuring the corresponding knowledge in the field of organocatalysis, we aimed to combine cinchona (thio)squaramide and thiourea organocatalysts with copper(II), nickel(II), and silver(I) salts in reactions that are relevant in pharmaceutical aspects, such as Michael addition, Friedel-Crafts reaction and A 3 coupling reaction. Furthermore, we have found explanations for the formation and activity of the prepared organocatalyst-metal complexes via the applied quantum chemical calculations linked to analytical techniques.…”

“…Transition metals combined with organocatalysts can merge their superior qualities to promote reaction systems that can lead to new transformations [36–45] . This way, multicomponent or multistep reactions could take place that cannot be realized without their combined application [46–57] …”

“…[ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ] This way, multicomponent or multistep reactions could take place that cannot be realized without their combined application. [ 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ]…”