Regioselectivity of Mercury-Promoted Oxacyclizations of Alkynyl Diols

Abstract

Supporting InformationS-3 II. Synthesis of diynyl triol (S,S)-6Preparation of (±)-8: HgCl 2 (90 mg; 0.33 mmol) and Mg 0 (3.65 g; 150 mmol) were added to a two-neck oven-dried 250 mL round bottom flask equipped with reflux condenser. A solution of propargyl bromide (0.4 mL) in Et 2 O (16 mL) was added. The resulting suspension was heated gently with a heating gun to initiate the reaction, resulting in bubbling which persisted after heating ceased. The flask was then cooled to 0 °C, before dropwise addition of the remaining propargyl bromide (5.2 mL; 50 mmol total) in Et 2 O (30 mL) over 20 min. The reaction continued to bubble upon and after addition of propargyl bromide. After stirring at 0 °C for 15 min, the grey Grignard solution was transferred via cannula to a flask containing propargyl aldehyde 7 2 (2.38 g; 12.6 mmol) in THF (62 mL) at -78 °C. The reaction was stirred at -78 °C for 3 h, after which time it was quenched by addition of sat'd aq. NH 4 Cl (20 mL) and allowed to warm to room temperature. The organic layer was separated and the aqueous layer was extracted with Et 2 O (3 x 20 mL). The combined organic extracts were washed with brine, dried over Na 2 SO 4 , filtered, and concentrated under reduced pressure to afford the crude product as a yellow oil, which was purified by silica gel flash column chromatography (20% EtOAc in hexanes) to afford racemic diynyl alcohol 8 as a clear, colorless oil (2.44 g; 10.7 mmol; 85% yield). O OBn H 7 R + OR OBn H H S Supporting Information S-4 1 H NMR for diynyl alcohol (±)-8: (600 MHz, CDCl 3 ) δ 7.39 -7.29 (m, 5H), 4.56 (s, 2H), 4.52 (dtd, J = 8.0, 5.9, 1.9 Hz, 1H), 3.60 (t, J = 7.0 Hz, 2H), 2.61 (m, 2H), 2.56 (td, J = 7.0, 1.9 Hz, 2H), 2.20 (d, J = 6.3 Hz, 1H), 2.11 (t, J = 2.6 Hz, 1H).Resolution of (±)-8 to prepare diynyl ester (R)-8 and diynyl alcohol (S)-9: Powdered 3Å molecular sieves (1.5 g) and Pseudomonas AK (1.12 g) were added to a solution of racemic diynyl alcohol 8 (2.24 g; 9.80 mmol) in hexanes (100 mL). Vinyl acetate (4.0 mL) was then added. The suspension was stirred and monitored for conversion by 1 H NMR spectroscopy.After 4 h, the reaction had reached 50% conversion by 1 H NMR. The reaction mixture was filtered through Celite, rinsed with CH 2 Cl 2 , and concentrated under reduced pressure to afford a pale-yellow oil. The crude reaction mixture was purified by silica gel flash column chromatography (18% EtOAc in hexanes) to afford diynyl ester (R)-9 (1.10 g; 4.07 mmol; 42% yield) and diynyl alcohol (S)-8 (854 mg; 3.74 mmol; 38% recovery; 80% combined yield of 8 and 9). MTPA-esters confirmed the stereochemical assignment and purity of (S)-8 (er > 95:5; the other stereoisomer was not visible). Data for diynyl ester (R)-9: [α] D 25 +48.8 (c=1.0, CHCl 3 ) 1 H NMR (600 MHz, CDCl 3 ) δ 7.39 -7.30 (m, 5H), 5.50 (app. tt, J = 6.3, 2.0 Hz, 1H), 4.56 (s, 2H), 3.60 (t, J = 7.1 Hz, 2H), 2.67 (dd, J = 6.2, 2.6 Hz, 2H), 2.56 (td, J = 7.1, 2.0 Hz, 2H), 2.11 (s, 3H), 2.05 (t, J = 2.7 Hz, 1H).OH OBn

Eight-Membered Rings With One Oxygen Atom

“…The structural elucidation of the corresponding acetate derivative 224 was possible through NMR spectroscopy, including COSY, HMBC, HMQC and NOESY correlations of the protons at the C-O-C portion of the oxocane ring. 175 (R)-9-Hydroxypentadecan-3-one (R)-225 underwent a diastereoselective reductive cyclization mediated by Et 3 SiH and TMSOTf in dichloromethane to furnish exclusively the cyclic eight-membered ether (−)-cis-lauthisan 95. Similarly (S)-9hydroxypentadecan-4-one (S)-225 produced (+)-isolaurepan 191 (Scheme 35).…”

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

“…Interestingly when 1.4-dihydroxy-5-alkyne derivatives were subjected to a Hg(OTf) 2 -catalyzed cyclization then oxacyclization takes place to form tetrahydropyran derivatives ( Scheme 43 ) [ 101 ]. Later it was shown that alkynyl diol 150 when treated with 20 mol % Hg(OTf) 2 followed by Et 3 SiH afforded bispyranoyl ketone 151 , but when Hg(OTf) 2 was increased (1 equiv) then fused pyran-oxocane derivative 152 was isolated [ 102 ].…”

Research on promoting the asymmetric reaction of phenylacetylene with aldehydes by chloramphenicol base ligands

“…The amino group and two hydroxyl groups in its molecule can be modified by simple steps. According to the literature investigation, chloramphenicol base derivatives as catalysts show good activity and selectivity in many organic reactions 31–35 . The rigidity of the chloramphenicol base can be increased by replacing the hydrogen on the amino group with a cycloalkyl group to give ligands 2a and 2b (Scheme 1).…”

“…According to the literature investigation, chloramphenicol base derivatives as catalysts show good activity and selectivity in many organic reactions. [31][32][33][34][35] The rigidity of the chloramphenicol base can be increased by replacing the hydrogen on the amino group with a cycloalkyl group to give ligands 2a and 2b (Scheme 1). In addition, the nitro group in the structure of chloramphenicol base has a strong electron-withdrawing ability, and it may reduce the electron cloud density on the amino group, resulting in a decrease in the coordination ability of the nitrogen atom to zinc, which may affect its catalytic properties.…”