Tandem Nucleophilic Addition/Oxa‐Michael Reaction for the Synthesis of cis‐2,6‐Disubstituted Tetrahydropyrans

Abstract

A Lewis acid catalyzed tandem nucleophilic addition/oxa-Michael reaction was developed for the synthesis of cis-2,6disubstituted tetrahydropyran (THP) derivatives in good [a]

An Efficient Stereoselective Synthesis of cis-2,6-Disubstituted Tetrahydropyrans via Gold-Catalyzed Meyer–Schuster Rearrangement/Hydration/oxa-Michael Addition Sequence

“…), Ph 3 PAuCl (4.9 mg, 0.0099 mmol, 10 mol%) and AgNTf 2 (3.9 mg, 0.0099 mmol, 10 mol%) in ClCH 2 CH 2 Cl (5 mL) furnished cis-14a (20 mg, 61%) as a colorless oil (hexane:CH 2 Cl 2 = 6:1). The 1 H-NMR and 13 C-NMR data are identical with reported values [13].…”

“…During the equilibration between the reverse oxa-Michael addition and oxa-Michael addition (Scheme 10), the bulky substituent (α,β-enone) occupies a pseudo-equatorial position to avoid 1,3-diaxial interactions (G-II). As the α,β-enone group is bulkier than hydrogen, it tends to take a pseudo-equatorial position (G-I) rather than a pseudoaxial position (G-II) to avoid 1,3-diaxial interaction, resulting in stereoselective synthesis of cis-2,6disubstituted tetrahydropyran 14 [13,27].…”

“…1 H and 13 C NMR spectra were recorded with a JEOL JNM-AL300 (Japan Electron Optics Laboratory Co., Ltd., Tokyo, Japan) or BRUKER AV-300 spectrometer (Bruker, Billerica, MA, USA) at room temperature, with tetramethylsilane as an internal standard (CDCl 3 solution). Chemical shifts were recorded in ppm and coupling constants (J) in Hz.…”

“…For example, decytosporides A [3,4], aspergillide [5,6] and phorboxazole A [7] have important biological activities, including anti-tumor activity against the A549 tumor cell line, potent cytotoxic activity against murine platelet leukaemia cells, and NIC anti-cancer activity (Figure 1). Therefore, a great deal of effort has been devoted to the development of synthetic methods for the synthesis of 2,6-cis-disubstituted tetrahydropyrans [8][9][10][11][12][13][14][15], which remains an important topic in organic synthesis.…”

“…For example, decytosporides A [3,4], aspergillide [5,6] and phorboxazole A [7] have important biological activities, including anti-tumor activity against the A549 tumor cell line, potent cytotoxic activity against murine platelet leukaemia cells, and NIC anti-cancer activity (Figure 1). Therefore, a great deal of effort has been devoted to the development of synthetic methods for the synthesis of 2,6-cisdisubstituted tetrahydropyrans [8][9][10][11][12][13][14][15], which remains an important topic in organic synthesis. We have developed an efficient synthesis of heterocyclic compounds (cyclic ethers 4,10 [16]/piperidines 5,11 [17]/azepanes 6,12 [18]) from propargylic alcohols 1-3 by strategic use of oxophilic (hard) gold (III) and π-philic (soft) gold (I) catalysts (Scheme 1).…”