Acid-catalysed intramolecular C-alkylation in βγ-unsaturated diazomethyl ketones. A new synthetic route to angularly fused cyclobutanones, bridged cyclopentanones, and γ-lactones

Abstract

Acid-induced decomposition of rigid polycyclic py-unsaturated diazomethyl ketones (2a and b) and (4a and b) is shown to give, in excellent yields, the respective angularly fused unsaturated cyclobutanones (5a and b) and (6a and b) and/or the rearranged bridged hydroxycyclopentanones (7a) and (9a) depending upon the reagents, reaction conditions, and the nature of the substrates. Under certain conditions (5a) and (7a) undergo rearrangement to 3a-methyl-l,2,3,3a,6,7-hexahydropentaleno[l,6a-aJnaphthalen-4-one (1 2a). The unsaturated cyclobutanones undergo stereoselective catalytic hydrogenation to the respective trans-angularly substituted hydrophenanthrene and hydrofluorene cyclobutanones (13a and b) and (14a and b) which on facile gayer-Villiger oxidation produce the y-lactones (18a and b) and (1 9a and b). The unsaturated cyclobutanones (5a and b) also afford the respective y-lactones (20a and b) on oxidation with alkaline hydrogen peroxide. * For application of this reaction for the preparation of a D-norsteroidal skeleton see ref. 9.

First Diastereoselective Synthesis of (−)-Methyl Thyrsiflorin A, (−)-Methyl Thyrsiflorin B Acetate, and (−)-Thyrsiflorin C

“…Initial attempts to effect the cyclization of α-diazoketone 19 , Rh 2 (OAc) 4 , BF 3 ·OEt 2 , trifluoroacetic acid/HClO 4 , and HClO 4 , all gave disappointing results. Eventually, the desired intramolecular insertion was successfully carried out by a slow addition of diazoketone 19 over a refluxing solution of bis( N - tert -butylsalicylaldiminato)copper(II) (BTBSACu) in toluene to give ketone 20 in 82% yield.…”

“…Chromatography of the crude using hexanes-ethyl acetate (8:2) afforded 23 mg of the unreacted ketal impurity 18 and the ketone 20 as a white solid (162 mg, 82%): mp 185-186 °C (from ether); [R] 20 D CHCl3); IR (KBr) 1725 cm -1 ; 1 H NMR (400 MHz; CDCl3) δ 3. 98-3.65 (4H, m, ketal) 29 (s), 47.98 (s), 47.48 (d), 41.82 (t), 41.59 (t), 39.47 (d), 36.56 (t), 34.06 (s), 33.71 (q), 33.05 (s), 32.20 (s), 31.89 (t), 29.19 (t), 21.37 (q), 18.41 (t), 17.75 (t), 17.53 (q), 10.97 (q); MS (EI) m/z 344 (M + , 100), 316 (15); HRMS C22H32O3 requires 344.2351, found 344.2352H, 9.36. Found: C, 76.82;H, 9.45.…”