Enantiodivergent conversion of chiral secondary alcohols into tertiary alcohols

Abstract

From receptors in the nose to supramolecular biopolymers, nature shows a remarkable degree of specificity in the recognition of chiral molecules, resulting in the mirror image arrangements of the two forms eliciting quite different biological responses. It is thus critically important that during a chemical synthesis of chiral molecules only one of the two three-dimensional arrangements is created. Although certain classes of chiral molecules (for example secondary alcohols) are now easy to make selectively in the single mirror image form, one class-those containing quaternary stereogenic centres (a carbon atom with four different non-hydrogen substituents)-remains a great challenge. Here we present a general solution to this problem which takes easily obtainable secondary alcohols in their single mirror image form and in a two-step sequence converts them into tertiary alcohols (quaternary stereogenic centres). The overall process involves removing the hydrogen atom (attached to carbon) of the secondary alcohol and effectively replacing it with an alkyl, alkenyl or aryl group. Furthermore, starting from a single mirror image form of the secondary alcohol, either mirror image form of the tertiary alcohol can be made with high levels of stereocontrol. Thus, a broad range of tertiary alcohols can now be easily made by this method with very high levels of selectivity. We expect that this methodology could find widespread application, as the intermediate tertiary boronic esters can potentially be converted into a range of functional groups with retention of configuration.

Enantiospecific sp2–sp3 coupling of secondary and tertiary boronic esters

“…We therefore tested enantioenriched, benzylic 40,41 and non-benzylic 42 tertiary boronic esters 1k-n in our process ( Table 2) and found that the desired products 2k-n were obtained in good yields and complete stereospecificity, demonstrating the power of the new methodology. As these boronic esters were readily prepared in essentially enantiopure form, the furyl-coupled products were also obtained in similarly enantiopure form as well.…”

“…A range of enantioenriched secondary 39 and tertiary boronic esters [40][41][42] were then prepared by lithiation-borylation methodology or by hydroboration ( Figure 2, see SI for details) and subsequently tested under these optimized reaction conditions (Table 1). Figure 2.…”

Chiral -Hydroxyalkyloxazolines as Ligands in the Enantioselective Addition of Diethylzinc to Aldehydes

“…Among the challenges found in the stereoselective synthesis of organic molecules, it is included the development of low cost ligands and catalysts. [1][2][3][4] Here we report our results involving the addition of diethylzinc to aryl aldehydes using β- …”

Borreagentien für die orthogonale Funktionalisierung mithilfe von Suzuki‐Miyaura‐Kreuzkupplungen

“…Nun, da die Reaktivität von Organoborverbindungen in aufeinanderfolgenden Suzuki-Miyaura-Kupplungen eingestellt werden kann, sollte dieses Konzept zahlreiche Anwendungen finden, etwa in der Tandemkatalyse und der asymmetrischen Synthese. [11] Solche Studien werden außerdem Untersuchungen zur Einstellung der Reaktivität von anderen metallorganischen Verbindungen durch maßgeschneiderte Liganden anregen. [12] Diese Vorschriften sollten leistungsfähige Reagentien für die Synthese von Naturstoffen und hochmolekularen p-konjugierten Oligomeren mit genau definierter Struktur liefern und werden so zu Fortschritten in benachbarten Wissenschaftsgebieten beitragen.…”