Facile and Highly Diastereoselective Synthesis of syn‐ and cis‐1,2‐Diol Derivatives from Protected α‐Hydroxy Ketones

Abstract

An efficient method for the synthesis of monoprotected syn‐ or cis‐1,2‐diol derivatives by reduction of easily accessible α‐(2,2,6,6‐tetramethylpiperidinyloxy) ketones is reported. The α‐(tetramethylpiperidinyloxy) group as the stereodirecting group induces in unhindered acyclic or cyclic ketones complete syn‐ or cis‐diastereoselectivity, respectively, with L‐Selectride. For more hindered derivatives, where L‐Selectride becomes unreactive, LiAlH4 proved effective, essentially showing the same high selectivity. The diastereoselectivity of the reduction can be rationalized for acyclic ketones by the Felkin–Anh model, whereas for cyclic substrates, attack from the face opposite to the tetramethylpiperidinyloxy group predictably prevails with high selectivity regardless of the substitution pattern. The liberation of free diols was achieved by reductive N–O bond cleavage of the alkoxyamine unit.

Tandem Anionic oxy‐Cope Rearrangement/Oxygenation Reactions as a Versatile Method for Approaching Diverse Scaffolds

“…Adding allylmagnesium chloride or Superhydride after radical oxygenation provided diene 12 a or alcohols 14 a , l , m with essentially complete diastereoselectivity. The high selectivity can be rationalized by the Felkin–Anh model, with the alkoxyamine unit serving as the large group . The resulting products show good potential for further transformations, as illustrated by ring‐closing metathesis of 12 a , providing cycloheptene 13 a in essentially quantitative yield, or reductive removal of the alkoxyamine unit leading to syn ‐diols 15 a , l , m .…”

Enolate-Based Regioselective Anti-Beckmann C–C Bond Cleavage of Ketones

“…A low 6% yield of cleavage product 32a was obtained by nitrosation of the lithium enolate generated by transmetalation of kinetic TMS enol ether 31b together with 27% of 33 . Hydroxyimino ester 32a was isolated as a 1:1 diastereomeric mixture, likely caused by epimerization at C2 of menthone . The isomeric thermodynamic silyl enol ether 31c afforded in contrast 59% of opened oxime ester 32b together with 16% of 32a .…”

Tandemreaktionen aus anionischer Oxy‐Cope‐Umlagerung und Oxygenierung als vielseitiger Zugang zu verschiedenartigen Gerüsten

“…zu den Alkoholen 14 a,l,m . Die Stereochemie kann durch das Felkin‐Anh‐Modell mit der Alkoxyamineinheit als größter Gruppe erklärt werden . Die resultierenden Produkte zeigen gutes Potential für weitere Transformationen, wie Ringschlussmetathese von 12 a zum Cyclohepten 13 a oder reduktive Spaltung der Alkoxyamineinheit, die zu den syn ‐Diolen 15 a,l,m führt.…”

“…Diese Reaktion ermçglicht darauffolgend eine Radkalcyclisierung mit dem aromatischen Ring (siehe Hintergrundinformationen zu einem mechanistischen Vorschlag). a-(Aminoxy)keton 2 l, das sowohl zur 5-endo-als auch 5-exo-Cyclisierung befähigt ist, reagierte in Gegenwart von 50 mol % TEMPO bevorzugt im 5-exo-Modus zum 1,2,3-tri- [17] Die resultierenden Produkte zeigen gutes Potential für weitere Transformationen, wie Ringschlussmetathese von 12 a zum Cyclohepten 13 a oder reduktive Spaltung der Alkoxyamineinheit, die zu den syn-Diolen 15 a,l,m führt.…”