Geminal Acylation with Methyl-Substituted Analogues of 1,2-Bis[(trimethylsilyl)oxy]cyclobutene

Abstract

BF 3 ‚Et 2 O-catalyzed geminal acylation of ketones and acetals with 3-methyl-1,2-bis[(trimethylsilyl)oxy)]cyclobutene (3) provided methylcyclopentanediones in yields that ranged from 40 to 94%. The best substrates were unhindered cyclohexanones. With acetals, stereochemical preferences in the initial Mukaiyama-like aldol step giving cyclobutanones translated into the stereochemistry of the ultimate cyclopentanedione products. With ketones, equilibration of the initial cyclobutanone compounds resulted in cyclopentanedione products with a different stereochemical preference. The gem-dimethylcyclobutene reagent 4 reacted with ketones to give gem-dimethylcyclopentanediones in modest yield. The process was much more stereochemically efficient than the reaction with 3. Rearrangement from the initial cyclobutanone compound was partially diverted toward air-sensitive 3-furanone compounds and ring-opened 1,2-diones. Only furanones (e.g., 52 and 53) were isolated from reactions with the tetramethylcyclobutene 51.

Synthesis of 6-alkyl analogues of the 1-azabicyclo[4.3.0]nonan-2-one system by a strategy of geminal acylation and Beckmann rearrangement

“…The Lewis acid catalyzed geminal acylation using 1,2-bis-[(trimethylsilyl)oxy]cyclobutene (7) 5- 11 or methylated analogues such as 8 [11][12][13] is now a well-established process for the formation of a 2,2-disubstituted cyclopentane-1,3-dione. Geminal acylation using 7 has been exploited in the syntheses of a number of natural products and other structurally interesting molecules.…”

“…For 14: pale yellow liquid; ν max (film)/cm Ϫ1 2958 (broad), 1764 and 1722; δ (12), 125 (14), 112 (100), 111 (37), 107 (15), 81 (13), 55 (31), 43 (22) (11), 173 (24), 155 (57), 154 (13), 153 (12), 145 (16), 111 (97), 101 (100), 83 (22), 69 (52), 57 (19), 55 (45), 45 (26), 43 (33) and 41 (36).…”

“…For 20: white solid; mp 187-189 ЊC; ν max (Nujol)/cm Ϫ1 3425, 1713 and 1657; δ H 6.94 (1 H, broad s, NH), 2.69 (4 H, s, 2-H and 3-H) and 1.80-1.52 (10 H, m); δ C 208.9 (0, C-1), 171.6 (0, C-4), 63.3 (0, C-6), 32.0 (2, C-2), 31.6 (2C, 2, C-7 and C-11), 26.2 (2, C-3), 21.8 (2C, 2, C-8 and C-10) and 17.7 (2, C-9); m/z 181.1080 (0.1%, M ϩ , C 10 H 15 NO 2 requires 181.1102), 153 (62), 110 (18), 98 (59), 97 (100), 96 (16), 82 (18), 81 (11), 69 (34), 57 (22), 56 (12), 55 (17), 54 (41), 41 (34), 28 (39) and 27 (35).…”

“…Following the procedure for 20, NH 2 OSO 3 H (23.4 mg, 0.207 mmol) and 25 (25.5 (25), 194 (15), 154 (11), 152 (12), 125 (28), 124 (65), 110 (30), 97 (23), 96 (31), 86 (22) (20), 152 (28), 138 (25), 125 (57), 110 (59), 100 (14), 97 (33), 96 (61), 69 (100), 55 (31) and 41 (54).…”

“…The solvent was removed under vacuum. Flash chromatography (50% acetone-hexanes) gave 32 (128 mg, 62%) as a white solid: mp 115-117 ЊC; ν max (CCl 4 )/cm Ϫ1 3195 (broad), 1729 and 1674; (12), 126 (31), 112 (25), 98 (100), 97 (48), 96 (30), 82 (37), 57 (24), 56 (22), 55 (20), 42 (58) and 41 (25).…”