Enantioselective Synthesis of Oxetanes Bearing All‐Carbon Quaternary Stereocenters via Iridium‐Catalyzed C−C Bond‐Forming Transfer Hydrogenation

Abstract

Taming the Oxetane Oxetanes bearing all-carbon quaternary stereocenters are readily prepared through the iridium catalyzed anti-diastereo- and enantioselective C-C coupling of primary alcohols and isoprene oxide. Based on this methodology, an oxetane containing analogue of haloperidol was prepared. A related azetidine formation also is described.

An Overview of Saturated Cyclic Ethers: Biological Profiles and Synthetic Strategies

“…Impressive synthetic approaches toward C–C bond-forming hydrogenations and transfer hydrogenations were developed. Guo et al [84] achieved access to oxetanes bearing all-carbon quaternary stereocenters readily prepared through the iridium catalyzed anti-diastereo and enantioselective C–C coupling of primary alcohols and isoprene oxide (Scheme 8). A group of primary alcohols 30 were exposed to isoprene oxide (300 mol%) and potassium phosphate (5 mol%) in the presence of the chromatographically purified π-allyliridium C,O-benzoate complex modified by ( S )-Tol-BINAP in a tetrahydrofuran solvent at 60 °C to give adducts 31 .…”

“…A group of primary alcohols 30 were exposed to isoprene oxide (300 mol%) and potassium phosphate (5 mol%) in the presence of the chromatographically purified π-allyliridium C,O-benzoate complex modified by ( S )-Tol-BINAP in a tetrahydrofuran solvent at 60 °C to give adducts 31 . Conversion of the diol-containing adducts to the corresponding oxetanes 32 were accomplished through highly chemoselective tosylation of the primary alcohol moiety followed by SN 2 cyclisation [84].…”

Catalytic Nucleophilic Allylation Driven by the Water–Gas Shift Reaction

“…19 Through the use of these iridium catalysts, the formation of enantioenriched products containing quaternary stereocenters, 20 the hydroxylmethylation of allylic acetates by enantio-topic π -facial discrimination, 21 and asymmetric allylation of glycidols while avoiding the common match-mismatch concerns 22 can be efficiently conducted. Also highlighted is the precise chemoselectivity that this method entails as demonstrated through the enantioselective allylation at the site of a single alcohol in a polyol without the need for protecting groups.…”

Enantioselective Total Synthesis of Andrographolide and 14‐Hydroxy‐Colladonin: Carbonyl Reductive Coupling and trans‐Decalin Formation by Hydrogen Transfer

“…[8] In the course of these studies,adivergent outcome in the intramolecular Sakurai allylation [15] used to prepare Fragment A from compound 4 was observed (Scheme 1). Compound 4, which is prepared in 3steps via isoprene oxide-mediated tert-(hydroxy)-prenylation [5] of commercially available 5-hydroxy-2-pentanone,e xists in equilibrium with its five-mem-bered lactol. Using ZnCl 2 as the Lewis acid, intramolecular Sakurai allylation [15] occurs by way of an endocyclic oxacarbenium ion to form the [2.2.1]oxabicycle Fragment A. However,u sing BF 3 •OEt 2 as the Lewis acid, Fragment A ring opens and eliminates to deliver the conjugated diene iso-Fragment A.Access to iso-Fragment A raised the possibility of further broadening our convergent approach to terpenoid construction by opening linear divergent routes to other terpenoid natural products through successive Diels-Alder cycloaddition-olefin reduction to generate a trans-decalin motif,a si nitially communicated in our total synthesis of isoiresin.…”