Compound 1

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Compound data: 1H NMR Rotamer A

Compound data: 1H{19F} NMR Rotamer A

Compound data: 13C NMR Rotamer A

Compound data: 13C{19F} NMR Rotamer A

Compound data: 19F NMR

Compound data: 19F{1H} NMR

Compound data: 1H NMR Rotamer B

Compound data: 1H{19F} NMR Rotamer B

Compound data: 13C NMR Rotamer B

Compound data: 13C{19F} NMR Rotamer B

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

An oven-dried reaction vessel (4 or 9 mL screw-cap vial) equipped with a stirring bar was allowed to cool to room temperature under vacuum. Then activated 4 Å MS (crushed, 50 mg), [Rh-2] (and solid substrates, 1.0 equiv.) were added under air. The vial was then depressurized and pressurized with argon gas three times prior the addition of dry tetrahydrofuran (1 M) (and liquid substrates – distilled over CaH₂, 1.0 equiv.). Upon the addition of 4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.0 – 4.0 equiv. as indicated), the glass vial was placed in a 150 mL stainless steel autoclave under argon atmosphere. The autoclave was pressurized and depressurized with hydrogen gas three times before the indicated pressure was set. The reaction mixture was stirred at the indicated temperature for 24 h. After the autoclave was carefully depressurized, trifluoroacetic anhydride (3.0 equiv.) and CH₂Cl₂ (0.5 mL) were added to the crude mixture and stirring was continued for 10 min at room temperature. Alternatively, di-tert-butyl dicarbonate (3.0 equiv.), triethyl amine (3.0 equiv.) and CH₂Cl₂ (0.5 mL) were added to the reaction mixture and stirring was continued for 2 h at room temperature. The crude was then filtered over fritted funnel and the remaining solid was washed with ethyl acetate (2×5 mL). The combined solution was concentrated under reduced pressure and submitted to column chromatography (pentane/ethyl acetate or pentane/dichloromethane) to obtain the final product. The indicated diastereoselectivities were determined by GC analysis or from the ¹⁹F NMR spectrum immediately after the reaction. NMR yield was calculated using hexafluorobenzene (20 μL, 0.173 mmol) as internal standard. Compound 1 was prepared following general procedure outlined above on 1 mmol scale, 0.5 mol% catalyst, 2 mmol HBpin, 1 M THF at 25 °C, purification with 0-40% ethyl acetate in pentane. The product was isolated as a colorless oil (162 mg, 0.81 mmol, 81% (volatile compound, 92% NMR yield)). The product was present as a ~1:1 mixture of amide bond rotamers. Rotamer A: ¹H NMR (600 MHz, Toluene-d₈, 299 K) δ 3.94 (dtt, J = 47.0, 5.6, 2.2 Hz, 1H), 3.63 (ddd, J = 13.8, 8.9, 5.6 Hz, 1H), 3.01 (d, J = 14.3 Hz, 1H), 2.89 (dd, J = 26.0, 13.8 Hz, 1H), 2.65 – 2.59 (m, 1H), 1.39 – 1.28 (m, 2H), 1.14 – 0.95 (m, 1H), 0.86 – 0.77 (m, 1H); ¹H{¹⁹F} NMR (600 MHz, Toluene-d₈, 299 K) δ 3.94 (tt, J = 5.6, 2.2 Hz, 1H), 3.63 (dd, J = 13.8, 5.6 Hz, 1H), 3.01 (d, J = 14.3 Hz, 1H), 2.89 (dd, J = 13.8, 2.2 Hz, 1H), 2.61 (ddd, J = 14.3, 8.8, 3.1 Hz, 1H), 1.39 – 1.28 (m, 2H), 1.11 – 0.97 (m, 1H), 0.87 – 0.78 (m, 1H); ¹³C NMR (151 MHz, Toluene-d₈, 299 K) δ 155.90 – 155.49 (m), 117.18 (q, J = 288.2 Hz), 85.33 (d, J = 176.5 Hz), 46.73 (d, J = 25.4 Hz), 45.13 (q, J = 3.5 Hz), 29.26 (d, J = 21.1 Hz), 21.45 (d, J = 4.4 Hz); ¹³C{sel-¹⁹F at -185 ppm} NMR (151 MHz, Toluene-d₈, 299 K) δ 155.96 – 155.39 (m), 117.18 (q, J = 288.2 Hz), 85.33, 46.73, 45.13 (q, J = 3.5 Hz), 29.26, 21.45; ¹⁹F NMR (564 MHz, Toluene-d₈, 299 K) δ -69.21, -184.91 – -185.20 (m); ¹⁹F{¹H} NMR (564 MHz, Toluene-d₈, 299 K) δ -69.21, -185.07. Rotamer B: ¹H NMR (600 MHz, Toluene-d₈, 299 K) δ 3.89 (dtt, J = 47.0, 5.3, 2.0 Hz, 1H), 3.52 (dt, J = 13.4, 4.8 Hz, 1H), 3.30 (ddd, J = 14.3, 8.4, 5.3 Hz, 1H), 2.76 (ddd, J = 26.0, 14.3, 2.0 Hz, 1H), 2.59 – 2.53 (m, 1H), 1.39 – 1.27 (m, 2H), 1.13 – 0.94 (m, 1H), 0.86 – 0.78 (m, 1H); ¹H{¹⁹F} NMR (600 MHz, Toluene-d₈, 299 K) δ 3.89 (tt, J = 5.3, 2.0 Hz, 1H), 3.52 (dt, J = 13.4, 4.8 Hz, 1H), 3.30 (dd, J = 14.3, 5.3 Hz, 1H), 2.76 (dd, J = 14.3, 2.0 Hz, 1H), 2.56 (ddd, J = 13.4, 9.6, 3.2 Hz, 1H), 1.38 – 1.29 (m, 2H), 1.10 – 0.97 (m, 1H), 0.86 – 0.77 (m, 1H); ¹³C NMR (151 MHz, Toluene-d₈, 299 K) δ 156.16 – 155.39 (m), 117.15 (q, J = 288.6 Hz), 85.22 (d, J = 176.6 Hz), 48.85 (dq, J = 25.4, 3.5 Hz), 43.03, 29.11 (d, J = 20.9 Hz), 20.21 (d, J = 4.2 Hz); ¹³C{sel-¹⁹F at -185 ppm} NMR (151 MHz, Toluene-d₈, 299 K) δ 155.98 – 155.44 (m), 117.16 (q, J = 288.6 Hz), 85.22, 48.85 (q, J = 3.5 Hz), 43.03, 29.11, 20.21; ¹⁹F NMR (564 MHz, Toluene-d₈, 299 K) δ -68.46 (d, J = 2.8 Hz), -185.59 – -185.88 (m); ¹⁹F{¹H} NMR (564 MHz, Toluene-d₈, 299 K) δ -68.46 (d, J = 3.1 Hz), -185.74. ESI-MS: calculated [C₇H₉NOF₄ +Na]⁺: 222.0518, found: 222.0522. IR ν = 2955 (w), 1689.7 (s), 1465.9 (w), 1435.1 (w), 1373.3 (w), 1180.5 (s), 1141.9 (s), 1087.9 (m), 1003 (w), 972.1 (w), 910.4 (w), 756.1 (m), 748.4 (m), 732.9 (m), 648.1 (w). In order to prove whether the fluorine atom is occupying an axial or equatorial position, we conducted a series of NMR studies that includes NOE and HF-HetNOE experiments. HF-HetNOE experiments showed unequivocally that the dominant orientation of the fluorine atom is axial.