New Polyhydroxylated Pyrrolidines Derived from Enantiopure 3,6-Dihydro-2H-1,2-oxazines

Abstract

[reaction: see text] Diastereoselective hydroborations of enantiopure 3,6-dihydro-2H-1,2-oxazines led to dihydroxy-substituted 1,2-oxazines. Samarium diiodide-induced N-O bond cleavage generated 1,4-amino alcohols which were recyclized to polyhydroxylated pyrrolidines which are potential glycosidase inhibitors.

Synthesis of New Enantiopure Bicyclic 1,2‐Oxazines by Addition of Lithiated Methoxyallene to Chiral Cyclic Nitrones

“…In previous experiments with 1,2-oxazines, stereoselective hydroboration has proved to be a very useful method to functionalize the enol ether double bond. [3] Application of this procedure to bicyclic 1,2-oxazine 7 furnished the expected hydroxy-substituted compound 9 in excellent diastereoselectivity (dr Ͼ 95:5) and good yield for the crude product (Scheme 5). However, after chromatography pure 9 was isolated in only 40% yield.…”

“…The authors also demonstrated that these 1,2-oxazines are valuable intermediates for the synthesis of enantiopure furan and pyran derivatives, [2] amino alcohols [3,4] and pyrrolidines. [3,4] …”

Chemoselectivity and the Curious Reactivity Preferences of Functional Groups

“…[18] On the other hand, direct cyclodehydration strategies are more straightforward, but come at the expense of costly reagents and scale-up issues. [19] One simple and elegant solution to this problem entails the chlorination of the alcohol with SOCl 2 followed by ring closure. While conceptually simple, the successful implementation of this strategy has been problematic because of the competition between N-and O-sulfinylation followed by side reactions, which ultimately lead to low yields of the desired cyclic amines.…”

“…Early work by Knochel and co-workers demonstrated that alkyl zinc reagents prepared by the reaction of zinc dust with an appropriate organohalide were not destroyed in the presence of acidic protons (pK a [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]. [157,158] In 2006, Uchiyama et al reported that the halogen-metal exchange of a haloarenes bearing acidic hydrogen atoms could be accomplished with tBu 4 ZnLi 2 without quenching the reagent or the resulting aryl zincate.…”

Enantiomerenreine Kohlenhydratmimetika durch Lewis‐Säure‐induzierte Umlagerung von 1,3‐dioxolanylsubstituierten 1,2‐Oxazinen

“…Zu erwähnen sind hier vor allem mehrfach hydroxylierte Pyrrolidinderivate, stereodefinierte Aminopolyole und substituierte Tetrahydrofuranderivate. [2] Alle Produkte sind wegen ihrer möglichen biologischen Aktivität, z. B. als Glycosidaseinhibitoren, interessant.…”