Robert A. Singer

Total Synthesis of Macrolactin A with Versatile Catalytic, Enantioselective Dienolate Aldol Addition Reactions

A highly convergent total synthesis of macrolactin A (1) utilizes modern asymmetric catalytic C-C coupling methods. The longest linear sequence in the route is 16 steps with an average yield of 86% per step. This total synthesis is valuable, because 1, which has been shown to possess activity against HIV, is not readily accessible from its natural source, a taxonomically unclassified deep-sea bacterium.

Metal versus silyl triflate catalysis in the Mukaiyama aldol addition reaction

Abstract A mechanistic study of the Mukaiyama aldol addition reaction employing benzaldehyde and hydrocinnamaldehyde along with a selection of Lewis acids including BF 3 •OEt 3 , LiClO 4 , Yb(OTf) 3 , Sn(OTf) 2 , and Zn(OTf) 2 is presented. The results of experiments conducted with doubly-labeled silyl ketene acetals implicate a Lewis acidic silicon species and not the metals as the catalyst in the Mukaiyama aldol addition reaction.

An in situ procedure for catalytic, enantioselective acetate aldol addition. Application to the synthesis of (R)-(−)-epinephrine

Abstract We report an in situ preparation of catalyst 3 which substantially simplifies the experimental procedure for the enantioselective, catalytic acetate aldol addition reaction. The addition of Me 3 SiCl and Et 3 N circumvents the azeotropic removal of the released isopropanol upon treating ligands 1 and 2 with Ti(O i Pr) 4 . Importantly, this new procedure maintains the salient features of the catalytic process we originally described: high yields and enantioselectivities, low catalyst loads, and convenient reaction times and temperatures. We have applied the new procedure to an efficient synthesis of ( R )-(−)-epinephrine from commercially reagents in an overall yield of 45%.

Totalsynthese von Makrolactin A über vielseitige katalytische, enantioselektive Dienolat‐Aldoladditionen

Eine in hohem Mase konvergente Totalsynthese von Makrolactin A 1 wird vorgestellt, in der moderne Methoden zur asymmetrischen katalytischen C-C-Bindungsbildung eingesetzt werden. Die langste lineare Sequenz in dieser Synthese umfast 16 Schritte mit einer Durchschnittsausbeute von 86 % pro Schritt. Eine Totalsynthese von 1 ist unter anderem auch deshalb von Bedeutung, weil 1, das gegenuber HIV aktiv ist, nicht leicht aus seiner naturlichen Quelle, einem taxonomisch nicht klassifizierten Tiefsee-Bakterium, in groserer Menge erhalten werden kann.

Catalytic, enantioselective acetate aldol additions to α,β-ynals: Preparation of optically active propargylic alcohols

Abstract A catalytic, enantioselective acetate-aldol addition reaction of silyl ketene acetals with α,β-ynals and 3 mol % of a chiral Ti(IV) complex is described. This process provides access to optically active β-hydroxy-γ-alkynyl esters in 84–96% yields and 94–97% ees.

Advances in catalytic, enantioselective aldol addition reactions with novel Ti(IV) complexes

Global competition demands that new pharmaceuticals be prepared using cost-efficient and environmentally benign processes. The discovery and study of chemical reactions for applications in the synthesis of bioactive molecules is, therefore, of paramount importance. Advances in asymmetric catalysis should have an unquestionable impact on the development of chemotherapeutic agents. Here, the authors describe some recent developments from their laboratories in the general area of catalytic, enantioselective C C bond-forming reactions.

Distal Stereocontrol Using Guanidinylated Peptides as Multifunctional Ligands: Desymmetrization of Diarylmethanes via Ullman Cross-Coupling

We report the development of a new class of guanidine-containing peptides as multifunctional ligands for transition-metal catalysis and its application in the remote desymmetrization of diarylmethanes via copper-catalyzed Ullman cross-coupling. Through design of these peptides, high levels of enantioinduction and good isolated yields were achieved in the long-range asymmetric cross-coupling (up to 93:7 er and 76% yield) between aryl bromides and malonates. Our mechanistic studies suggest that distal stereocontrol is achieved through a Cs-bridged interaction between the Lewis-basic C-terminal carboxylate of the peptides with the distal arene of the substrate.