Compound 5

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Compound data: NMR

Compound data: Crystallographic data

Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

A solution of freshly prepared MgBr₂•Et₂O^A in a separate flask was quickly added via a Teflon cannula to the solution containing 1-lithio bicyclo[1.1.0]butane (3)^B. After stirring for 2 h at –78 °C, a solution of methyl 4-methylbenzenesulfinate 4 (2.20 g, 12.92 mmol, 1 equiv) in THF (13 mL) was added at a rate of 3.5 mL/min (syringe pump) and then the reaction mixture was stirred for 5 min at –78 °C and finally for 30 min at ambient temperature. NH₄Cl (saturated aqueous solution, 100 mL) was added and the organic layer was collected. The aqueous phase was washed with Et₂O (3× 100 mL) and then the combined organic phases were dried (MgSO₄), filtered, and concentrated under reduced pressure. The crude residue was purified by flash column chromatography (SiO₂; 60:40 pentane:EtOAc) to afford the BCB-sulfoxide 5 (avg. 1.30 g, avg. 52 % over 13 experiments) as a colorless oil which quickly solidifies to give a white – pale yellow crystalline solid^C (crystallization is best induced by holding a piece of dry ice against the side of the flask containing 5). Notes: (A) This should be prepared during the 1 h stir at ‒50 °C. MgBr₂•Et₂O was prepared as follows: A flame-dried nitrogen-flushed 250 mL flask, equipped with a reflux condenser, was charged with Mg turnings (3.06 g, 124 mmol, 9.6 equiv) and Et₂O (40 mL). 1,2-dibromoethane (2.67 mL, 31.02 mmol, 2.4 equiv) was added dropwise until reflux was initiated. The suspension was then cooled to 0 °C (ice/water) and the remaining 1,2-dibromoethane was added dropwise. After gas evolution had ceased, the mixture was stirred for additional 30 min at ambient temperature. Be careful to not cool the mixture too much since it can freeze to give a grey solid. This can be dissolved by heating the flask gently (warm water bath). The final solution should have two layers: a colorless top layer and a dark grey bottom layer. (B) A Teflon cannula is not a necessity but is the easiest to use. These can be prepared by cutting a piece of HPLC tubing to the required length and threading this through two appropriately sized suba-seals. We used BOLA PTFE tubing (ID 1.5 mm, OD 2.5 mm) purchased from Sigma−Aldrich. (C) The BCB-sulfoxide is slightly hygroscopic (but not enough to give problems when weighing and handling) so should be stored in a freezer under an inert atmosphere. TLC: R_f = 0.24 (60:40 pentane:EtOAc). ¹H NMR (500 MHz, CDCl₃) δ 7.56 (d, J = 8.1 Hz, 2H, 2× ArH), 7.32 (d, J = 8.1 Hz, 2H, 2× ArH), 2.42 (s, 3H, CH₃), 2.38 – 2.36 (m, 1H, (CH^aH^b)^a), 2.11 – 2.08 (m, 1H, (CH^aH^b)^b), 2.06 – 2.03 (m, 1H, CH), 1.38 – 1.36 (m, 1H, (CH^aH^b)^b),1.21 – 1.19 (m, 1H, (CH^aH^b)^a) ppm. ¹³C NMR (126 MHz, CDCl₃) δ 141.6 (ArC), 141.5 (ArC), 130.0 (ArCH), 124.6 (ArCH), 37.6 (CH₂^b), 34.1 (CH₂^a), 25.1 (C), 21.6 (CH₃), 8.6 (CH) ppm. HRMS (m/z): (ESI) calc’d for C₁₁H₁₂OSNa [M+Na]⁺: 215.0507, found: 215.0499. IR (solid state) ν_max: 3077, 3039, 2973, 2956, 2930, 1788. 1491, 1298, 1104, 1081, 1036, 1013, 809 and 771 cm⁻¹. X-ray Crystal Structure: CCDC number: 1835072.