Lewis Acid Mediated “endo-dig” Hydroalkoxylation–Reduction on Internal Alkynols for the Stereoselective Synthesis of Cyclic Ethers and 1,4-Oxazepanes

Abstract

Lewis acid mediated 5/6/7-endo-dig hydroalkoxylation-reduction cascade on internal alkynols gave an expedient, stereoselective synthesis of cyclic ethers and 1,4-oxazepanes. The strategy has been extended to the first examples of hydroalkoxylation-alkyne Prins-type cyclization cascade of alkyne-tethered alkynols, giving access to oxa-bicyclic scaffolds. This method was used as the key step in the stereoselective total synthesis of calyxolane A-B, as well as (±)-centrolobine and its homologue.

HFIP-Promoted Synthesis of Substituted Tetrahydrofurans by Reaction of Epoxides with Electron-Rich Alkenes

“…3-Methyl-3-phenyl-1-oxaspiro[ 4 , 5 ]decane ( 3bg ): colourless oil; purification by flash chromatography (hexane/EtOAc), 30% estimated yield (not purely isolated); 1 H NMR (300 MHz, CDCl 3 ): δ H = 7.36–7.30 (m, 4H), 7.26–7.23 (m, 1H), 4.05 (d, J = 8.7 Hz, 1H), 3.94 (d, J = 8.5 Hz, 1H), 2.12 (d, J = 12.6 Hz, 1H), 1.98 (dd, J = 12.6, 0.7 Hz, 1H), 1.79–1.7 (m, 5H), 1.61 (d, J = 2.7 Hz, 2H) 1.51 (d, J = 6.0 Hz, 3H), 1.46 (s, 3H) ppm; MS (EI): m / z 230(M + , 43%), 216 (16), 215 (100), 187 (59), 118 (19), 117 (25), 91 (14), 55 (30); HRMS (GC/MS-EI/Q-TOF): m / z calcd. for C 16 H 22 O 230.1671, found 230.1672.…”

“…In general, natural compounds containing tetrahydrofuran ring derivatives have been found in different classes of terrestrial and marine organisms [ 1 , 2 , 3 ]. One of these representative examples are Caloxylanes A and B, both isolated from the Caribbean marine sponge Calyx podatypa [ 4 , 5 ], or Corsifuran A, isolated from the heartwood of the tree Thespesia populnea [ 6 ]. Other examples are the lignans Fragransin C1 (among other compounds from the Fragransin family) [ 1 , 7 ] and Conocarpan [ 1 , 8 ], both having demonstrated to exhibit biological activity ( Figure 1 ).…”

Metal‐Free Intramolecular Hydroalkoxylation of Alkyne: Recent Advances

“…The reaction of ). [41] Further, the developed method was applied in the synthesis of 1,4-oxazepanes. N-tethered alkynols 46 upon reaction with 2 equivalents of TMSOTf and 1 equivalent of Et 3 SiH furnished corresponding 1,4-oxazepanes 47 in good yield (Scheme 27).…”

Boron‐Catalyzed Hydroamination/Hydroallylation and Hydroamination/Hydrocyanation of Unactivated Alkynes

“…In addition, relatively simple alkynyl amines with no substituents on the linker between the nitrogen atom and alkyne were used in the investigation of these reactions . Recently, we reported the intramolecular hydroalkoxylation/hydroallylation and hydroalkoxylation/hydrocyanation by the main group metal catalyst, tris(pentafluorophenyl)borane [B(C 6 F 5 ) 3 ] (Scheme b) . Synthetically versatile allyl and cyano groups can be introduced in a second hydrofunctionalization.…”