Regiochemical Studies of the Ring Expansion Reactions of Hydroxy Azides with Cyclic Ketones

Abstract

The regiochemistry of ring expansions of 2-substituted cyclic ketones using 1,2-azidoethanol and 1,3-azidopropanol was examined. It was determined that the reactions of ketones with an adjacent methyl or ethyl group are generally unselective, but that bulkier substituents lead to preferential migration of the more highly substituted carbon. In addition, it was found that ketones bearing inductively electron-withdrawing substituents (OMe, Ph, Br) undergo selective migration of the less highly substituted carbon. For some substrates, alternative reaction pathways were also identified.

Regioselectivity Control of the Ring Opening of Epoxides With Sodium Azide in a Microreactor

“…of NaN 3 , and 2.2 equiv. of NH 4 Cl, resulting in a heterogeneous reaction mixture. However, in microreactors, in order to avoid clogging of the microchannels, a homogeneous reaction mixture is preferred.…”

“…Vicinal azido alcohols are versatile compouds in organic synthesis [1] because they not only constitute as components of biologically active natural products but also serve as important precursors in the synthesis of amino sugars [2], carboxylic nucleosides [3], lactams [4], oxazolines [5], and amino alcohols [6]. The method most employed to prepare 1,2-azido alcohols is azidolysis of the corresponding epoxides (Scheme 1) [7].…”

“…The method most employed to prepare 1,2-azido alcohols is azidolysis of the corresponding epoxides (Scheme 1) [7]. It uses aqueous solutions of sodium azide (NaN 3 ) and ammonium chloride (NH 4 Cl) or organic media with trimethylsilyl azide as the azide source. However, it generally requires long reaction times (12-48 h), and the formation of an azidohydrin is often accompanied by diol formation, toxic HN 3 formation in strong acidic medium, and lack of regioselectivity.…”

Oxidative Rearrangement of Cyclobutanone Derived <i>N</i>,<i>O</i>-Ketals Leading to Pyrrolidone Derivatives

“…The reaction represents an alternative to Schmidt reaction using hydroxyalkyl azides. [22][23][24][25][26][27][28] Studies of halogen-induced oxidative rearrangements of N,O-ketals were performed using 1a as a test substrate. Compound 1a was readily prepared by the condensation of cyclobutanone with a commercially available amino alcohol, 2-amino-3-phenylpropan-1-ol.…”

“…The iminium ether intermediate ii has ambident electrophilicity, and the C2 and C4 positions of the oxazoline ring can react with nucleophiles. [22][23][24][25][26][27][28][30][31][32][33] Methyl ether 3a′ is not produced, and therefore nucleophilic attack by MeOH on intermediate ii selectively occurs at the C2 position rather than the C4 position of the oxazoline ring, to give a possible intermediate iii, which affords alcohol 3a on aqueous work-up.…”