Synthesis of Five-, Six-, and Seven-Membered Heterocycles by Intramolecular Ring Opening Reactions of 3-Oxetanol Derivatives

Abstract

Intramolecular ring opening reactions of 2-phenyl-3-oxetanols have been studied. The starting materials were prepared by the photocycloaddition of benzaldehyde and various silyl enol ethers. The intramolecular nucleophile was either incorporated into the silyl enol ether prior to the Paternò−Büchi reaction (oxetanes 3, 16) or was later installed by functional group interconversion (oxetanes 5, 12). With anionic heteroatom nucleophiles (O, N, S) which were attached to the carbon atom C-3 of the trimethylsilyl-protected oxetanol via an alkyl chain, a substitution at the less substituted position C-4 was observed and the corresponding heterocycles (6, 8, 13, 19) were obtained in moderate to good yields (52−91%). Upon acid catalysis a ring opening of the Boc-protected 3-oxetanol 23 to cyclic carbonates occurred. The reaction did not proceed stereospecifically and resulted in a mixture of diastereomeric products 24 and 25.

Oxetanes as Versatile Elements in Drug Discovery and Synthesis

“…[63] Loy and Jacobsen documented the enantioselective Lewis acid mediated intramolecular ring opening of oxetanes.…”

Synthesis and cationic ring‐opening polymerization of oxetane monomer containing five‐membered cyclic carbonate moiety via highly chemoselective addition of CO2

“…Vinyloxetanes and alkynyloxetane undergo intramolecular ring‐expansion reactions to form 3,6‐dihydro‐ 2H ‐pyrans, 2,3‐dihydrofurans, and lactones . The ring‐opening reactions of oxetanes with stoichiometric amount of nucleophiles proceeded to give various alcohols such as aryl alkyl alcohols, γ‐amino alcohols, hydroperoxy alcohols, dialkylperoxy alcohols, chiral alcohols, and so on . Moreover, oxetane derivatives are used as functional monomers that can be converted to various kinds of linear, branched, and crosslinked polyoxetanes via cationic ring‐opening polymerization using catalytic amounts of Lewis acids.…”

“…15 The ringopening reactions of oxetanes with stoichiometric amount of nucleophiles proceeded to give various alcohols such as aryl alkyl alcohols, 16 γ-amino alcohols, 17 hydroperoxy alcohols, 18,19 dialkylperoxy alcohols, 20 chiral alcohols, [21][22][23] and so on. [24][25][26][27] Moreover, oxetane derivatives are used as functional monomers that can be converted to various kinds of linear, branched, and crosslinked polyoxetanes via cationic ring-opening polymerization using catalytic amounts of Lewis acids. For example, branched and hyperbranched polyoxetanes were synthesized from hydroxyl-substituted oxetanes in the presence of catalytic boron trifluoride diethyl etherate (BF 3 -Et 2 O) or trifluoromethanesulfonic acid (TfOH).…”

A Direct Synthesis of Highly Substituted π‐Rich Aromatic Heterocycles from Oxetanes

“…Optimization studies revealed that two equivalents of amine and longer reaction times were necessary to achieve acceptable yields. Lithiation of 2-bromophenol and addition to 3-oxetanone proceeded smoothly,a nd treatment of intermediate 11 with TFAp roduced 12, [18] albeit in disappointing yield owing to significant decomposition. With optimized conditions in hand, we further evaluated the substrate scope ( Table 2).…”