Thermal Chemistry of Bicyclo[4.2.0]oct-2-enes

Abstract

At 300 degrees C, bicyclo[4.2.0]oct-2-ene (1) isomerizes to bicyclo[2.2.2]oct-2-ene (2) via a formal [1,3] sigmatropic carbon migration. Deuterium labels at C7 and C8 were employed to probe for two-centered stereomutation resulting from C1-C6 cleavage and for one-centered stereomutation resulting from C1-C8 cleavage, respectively. In addition, deuterium labeling allowed for the elucidation of the stereochemical preference of the [1,3] migration of 1 to 2. The two possible [1,3] carbon shift outcomes reflect a slight preference for migration with inversion rather than retention of stereochemistry; the si/sr product ratio is approximately 1.4. One-centered stereomutation is the dominant process in the thermal manifold of 1, with lesser amounts of fragmentation and [1,3] carbon migration processes being observed. All of these observations are consistent with a long-lived, conformationally promiscuous diradical intermediate.

Gas Phase Thermal Reactions of exo-8-Cyclopropyl-bicyclo[4.2.0]oct-2-ene (1-exo)

“…The si/sr ratios for the more conformationally labile bicyclo[4.2.0]oct-2-enes are lower than those reported for bicyclo [3.2.0]hept-2-enes [3]. The relative kinetic importance of the observed exit channels for bicyclo[4.2.0]oct-2-enes labeled with a deuterium [4], methyl [5], or methoxy [3] at a migrating carbon is k ep > k f ≥ k 13 . The abbreviation k ep represents the rate of epimerization or one-centered stereomutation at C8; k f , the rate of direct fragmentation; k 13 , the total rate of [1,3]-sigmatropic migration including both si and sr products.…”

“…Bicyclo[2.2.2]oct-5-en-2-one (6), a known compound, was prepared in high purity but low yield by Diels-Alder reaction of 1,3-cyclohexadiene and 2-chloroacrylonitrile followed by base-catalyzed hydrolysis [4,13]. Tiffaneau-Demjanov rearrangement to bicyclo[3.2.2]non-6-en-2-one (7) [14,15] was accomplished in 30% overall yield.…”

“…Representations of this mechanism for the parent compound bicyclo[4.2.0]oct-2-ene are provided in Scheme 1, which shows that bicyclo[4.2.0]oct-2-ene can either isomerize via a [1,3]-shift to bicyclo[2.2.2]oct-2-ene or fragment to 1,3-cyclohexadiene and ethylene [4]. Due to the presence of a stereochemical marker at C8, the analog exo-8-cyclopropylbicyclo [4.2.0]oct-2-ene (1-exo) can undergo [1,3]-sigmatropic migration to the si (2-exo) and sr (2-endo) products or C8 epimerization to 1-endo (Scheme 2).…”

Development of Cyclobutene‐ and Cyclobutane‐Functionalized Fatty Acids with Inhibitory Activity against Mycobacterium tuberculosis

“…[8] In search of an efficient, general, and stereospecific approach to incorporation of four-membered rings onto a fatty acid backbone, we were drawn to methodology for modification of dichlorocyclobutanones. [9] Our approach is illustrated in detail for the preparation of analogs 1–4 (Scheme 1). The benzyl ester of 9-decenoic acid underwent cycloaddition with dichloroketene to afford one major dichlorobutanone ( 15 ), [10] which was only moderately stable towards purification, and was therefore directly reduced with sodium borohydride to furnish a mixture of stereoisomeric 2,2-dichloro-1-cyclobutanols.…”

“…Reduction of the dichlorocylobutanone 19 was achieved using a modification of a known procedure. [9,24] To a 0 °C solution of dichlorocyclobutanones 19 (1.5 g, 3.1 mmol) in i PrOH (45 mL) was added NaBH 4 (0.176 g, 4.65 mmol). The reaction was allowed to slowly warm to rt and stirred until starting material had disappeared (TLC, ~ 2.5h; byproducts tended to accumulate upon prolonged reaction).…”