*3.3. Nucleophilic Addition Reactions*

**(+)-(1***R***,2***R***,3***S***)-3-(Benzyloxy)-***N***-(***tert***-butyl)-2-methyl-2-phenylcyclopropane-1 carboxamide** (**23aaf**). Typical procedure B. An oven-dried 10 mL Weaton vial was charged with 18-crown-6 ether (5.3 mg, 20 μmol, 10 mol%), t-BuOK (134 mg, 1.20 mmol, 6.00 equiv.), benzyl alcohol (**25f**) (62.2 μL, 0.598 mmol, 2.92 equiv.), and anhydrous DMSO (10.0 mL). The mixture was stirred at room temperature for 1 min, and (1*S*,2*R*)-1-bromo-*N*-(*tert*-butyl)- 2-methyl-2-phenylcyclopropane-1-carboxamide (**20aa**) 63.5 mg (0.205 mmol, 1.00 equiv.) was added in single portion. The reaction mixture was stirred overnight at 80 ◦C, then solvent was removed in vacuum, and the residue was partitioned between water (15 mL) and EtOAc (15 mL). The organic layer was separated, and the aqueous phase was extracted with EtOAc (3 × 15 mL). Combined organic extracts were washed with brine, dried over MgSO4, filtered, and evaporated. Flash column chromatography on silica gel afforded the titled compound as a colorless solid, mp: 139.9–142.3 ◦C; Rƒ 0.32 (hexanes/EtOAc 4:1), [α] 25D = +14.5◦ (c 0.076, CH2Cl2). dr 60:1. Yield 52.0 mg (0.154 mmol, 76%). Spectral properties of this material were identical to those reported earlier for the racemic compound [67].

*(+)-(1R,2R,3S)-N-(tert-Butyl)-3-methoxy-2-methyl-2-phenylcyclopropane-1-carboxamide* (**23aaa**). Compound was obtained according to typical procedure B from 65.6 mg (0.211 mmol, 1.00 equiv.) of (1*S*,2*R*)-1-bromo-*N*-(*tert*-butyl)-2-methyl-2-phenylcyclopropane-1-carboxamide (**20aa**) employing methanol (**25a**) (24.2 μL, 0.598 mmol, 2.84 equiv.) as pronucleophile. Chromatographic purification afforded 53.1 mg (0.197 mmol, 93%) of the title compound as a colorless solid, mp: 120.6-122.9 ◦C; Rƒ 0.26 (hexanes/EtOAc 3:1), [α] 25D = +17.6◦ (c 0.068, CH2Cl2). dr 42:1. Spectral properties of this material were identical to those reported for the racemic compound [67].

*(+)-(1R,2R,3S)-N-(tert-Butyl)-3-ethoxy-2-methyl-2-phenylcyclopropane-1-carboxamide* (**23aab**). Compound was obtained according to typical procedure B from 63.2 mg (0.204 mmol, 1.00 equiv.) of (1*S*,2*R*)-1-bromo-*N*-(*tert*-butyl)-2-methyl-2-phenylcyclopropane-1-carboxamide (**20aa**), employing ethanol (**25b**) (35.0 μL, 0.600 mmol, 2.95 equiv.) as pronucleophile. Chromatographic purification afforded 42.3 mg (0.155 mmol, 78%) of the title compound as a white solid, mp: 130.4–131.6 ◦C; Rƒ 0.33 (hexanes/EtOAc 3:1), [α] 25D = +10.5◦ (c 0.048, CH2Cl2). dr 30:1. Spectral properties of this material were identical to those reported for the racemic compound [67].

*(-)-(1R,2R,3S)-N-(tert-Butyl)-2-methyl-2-phenyl-3-propoxycyclopropane-1-carboxamide* (**23aac**). Compound was obtained according to typical procedure B from 62.0 mg (0.200 mmol, 1.00 equiv.) of (1*S*,2*R*)-1-bromo-*N*-(*tert*-butyl)-2-methyl-2-phenylcyclopropane-1-carboxamide (**20aa**), employing *n*-propanol (**25c**) (44.9 μL, 0.600 mmol, 3.00 equiv.) as pronucleophile. Chromatographic purification afforded 52.9 mg (0.182 mmol, 91%) of the title compound as a colorless solid, mp: 122.1–124.9 ◦C; Rƒ 0.37 (hexanes/EtOAc 3:1), [α] 25D = −25.0◦ (c 0.044, CH2Cl2). dr 44:1. Spectral properties of this material were identical to those reported for the racemic compound [67].

*(+)-(1R,2R,3S)-N-(tert-Butyl)-3-(2-methoxyethoxy)-2-methyl-2-phenylcyclopropane-1-carboxamide* (**23aae**). Compound was obtained according to typical procedure B from 63.5 mg (0.205 mmol, 1.00 equi v.) of (1*S*,2*R*)-1-bromo-*N*-(*tert*-butyl)-2-methyl-2 phenylcyclopropane-1-carboxamide (**20aa**), employing 2-methoxyethanol (**25e**) (47.3 μL, 0.601 mmol, 2.93 equiv.) as pronucleophile. Chromatographic purification afforded 46.1 mg (0.152 mmol, 76%) of the title compound as a colorless solid, mp: 101.9–104.2 ◦C; Rƒ 0.34

(hexanes/EtOAc 1:1), [α] 25D = +70.0◦ (c 0.056, CH2Cl2). dr 58:1. Spectral properties of this material were identical to those reported for the racemic compound [67].

**(-)-(1***R***,2***R***,3***S***)-3-Methoxy-***N***,***N***,2-trimethyl-2-phenylcyclopropane-1-carboxamide** (**23aba**). Compound was obtained according to typical procedure B from 56.4 mg (0.201 mmol, 1.00 equiv.) of (1*S*,2*R*)-1-bromo-*N*,*N*,2-trimethyl-2-phenylcyclopropane-1 carboxamide (**20ab**), employing methanol (25.8 μL, 0.633 mmol, 3.15 equiv.) as pronucleophile. Chromatographic purification afforded 31.2 mg (0.134 mmol, 67%) as a colorless solid, mp: 108.9–111.3 ◦C, Rƒ 0.28 (hexanes/EtOAc 1:1), [α] 25D <sup>=</sup> −96.6◦ (c 0.089, CH2Cl2). dr >100:1. 1H NMR (500 MHz, CDCl3) *δ*<sup>H</sup> 7.34–7.12 (m, 5H), 4.25 (d, <sup>3</sup>*J*H,H = 5.8 Hz, 1H), 4.07 (s, 3H), 3.55 (s, 3H), 2.83 (s, 3H), 2.00 (d, <sup>3</sup>*J*H,H = 5.8 Hz, 1H), 1.65 (s, 3H); 13C NMR (126 MHz, CDCl3) *δ*<sup>C</sup> 167.5, 140.2, 127,4 (+, 2C), 126,9 (+, 2C), 125.7 (+), 66.8 (+), 57.3 (+), 36.3 (+), 36.0, 34.2 (+), 33.3 (+), 19.6 (+); FT IR (KBr, cm−1): 2972, 2929, 1734, 1637, 1479, 1460, 1430, 1377, 1265, 1230, 1143, 1070, 952, 847, 796, 763, 759, 740, 698, 624; HRMS (TOF ES): found 234.1498, calculated for C14H20NO2 (M+H)+ 234.1494 (1.7 ppm).

*(-)-(1S,2S,3R)-N,N-Diethyl-2-methyl-3-(3-methyl-1H-indol-1-yl)-2-phenylcyclopropane-1-carboxamide* (**23aci**). Compound was obtained according to typical procedure B from 62.0 mg (0.201 mmol, 1.00 equiv.) of (1*R*,2*S*)-1-bromo-*N*,*N*-diethyl-2-methyl-2 phenylcyclopropane-1-carboxamide (**20ac**), employing skatole (**25i**) (79.0 mg, 0.602 mmol, 3.00 equiv.) as pronucleophile. Chromatographic purification afforded 49.6 mg (0.138 mmol, 69%) as a colorless solid, mp: 116.2–117.5 ◦C, Rƒ 0.21 (hexanes/EtOAc 5:1), [α] 25D <sup>=</sup> −64.0◦ (c 0.050, CH2Cl2). dr 32:1. 1H NMR (500 MHz, CDCl3) *δ*<sup>H</sup> 7.58 (d, <sup>3</sup>*J*H,H = 7.8 Hz, 1H), 7.48 (d, <sup>3</sup>*J*H,H = 8.1 Hz, 1H), 7.41 (d, <sup>3</sup>*J*H,H = 7.8 Hz, 2H), 7.27 (d, <sup>3</sup>*J*H,H = 6.0 Hz, 1H), 7.24–7.20 (m, 1H), 7.14 (dd, <sup>3</sup>*J*H,H = 11.0, 3.9 Hz, 1H), 6.92 (s, 1H), 4.63 (d, <sup>3</sup>*J*H,H = 4.2 Hz, 1H), 3.76 (td, <sup>2</sup>*J*H,H = 14.3, <sup>3</sup>*J*H,H = 7.0 Hz, 1H), 3.66 (td, <sup>2</sup>*J*H,H = 13.9, <sup>3</sup>*J*H,H = 7.0 Hz, 1H), 3.34 (dq, <sup>2</sup>*J*H,H = 14.3, <sup>3</sup>*J*H,H = 7.0 Hz, 1H), 2.93 (dq, <sup>2</sup>*J*H,H = 13.9, <sup>3</sup>*J*H,H = 7.0 Hz, 1H), 2.55 (d, <sup>3</sup>*J*H,H = 4.2 Hz, 1H), 2.34 (s, 3H), 1.42 (s, 3H), 1.32 (t, <sup>3</sup>*J*H,H = 7.1 Hz, 3H), 0.86 (t, <sup>3</sup>*J*H,H = 7.1 Hz, 3H); 13C NMR (126 MHz, CDCl3) *<sup>δ</sup>*<sup>C</sup> 166.5, 140.3, 137.9, 129.4, 128.7, (+, 2C), 128.1 (+, 2C), 127.2 (+), 125.7 (+), 122.0 (+), 119.3 (+), 119.2 (+), 111.1, 110.5 (+), 42.3 (+), 41.9 (-), 40.2 (-), 37.0, 35.9 (+), 22.1 (+), 15.9 (+), 12.7 (+), 9.8 (+); FT IR (KBr, cm−1): 2972, 2927, 1639, 1465, 1379, 1309, 1263, 1230, 1143, 759, 740, 698; HRMS (TOF ES): found 360.2200, calculated for C24H28N2O (M+) 360.2202 (0.6 ppm).

*(-)-(1S,2S,3R)-N,N-Diethyl-2-methyl-2-phenyl-3-(1H-pyrrolo[2,3-b]pyridin-1-yl) cyclopropane-1-carboxamide* (**23acj**). Compound was obtained according to typical procedure B from 62.1 mg (0.201 mmol, 1.00 equiv.) of (1*R*,2*S*)-1-bromo-*N*,*N*-diethyl-2-methyl-2 phenylcyclopropane-1-carboxamide (**20ac**), employing 7-azaindole (**25j**) (71.0 mg, 0.600 mmol, 3.00 equiv.) as pronucleophile. Chromatographic purification afforded 35.4 mg (0.102 mmol, 50%) as a colorless solid, mp: 113.2–114.0 ◦C, Rƒ 0.42 (hexanes/EtOAc 2:1), [α] 25D <sup>=</sup> <sup>−</sup>5.2◦ (c 0.669, CH2Cl2). dr 20:1. 1H NMR (500 MHz, CDCl3) *<sup>δ</sup>*<sup>H</sup> 8.38 (dd, <sup>3</sup>*J*H,H = 4.7, <sup>4</sup>*J*H,H = 1.5 Hz, 1H), 7.90 (dd, <sup>3</sup>*J*H,H = 7.8 Hz, 1H), 7.65-7.51 (m, 2H), 7.34 (t, <sup>3</sup>*J*H,H = 7.7 Hz, 2H), 7.25 (d, <sup>3</sup>*J*H,H = 7.5 Hz, 1H), 7.22 (d, <sup>3</sup>*J*H,H = 3.6 Hz, 1H), 7.08 (dd, <sup>3</sup>*J*H,H = 7.8, 4.7 Hz, 1H), 6.47 (d, <sup>3</sup>*J*H,H = 3.5 Hz, 1H), 4.72 (d, <sup>3</sup>*J*H,H = 4.3 Hz, 1H), 3.85 (dq, <sup>2</sup>*J*H,H = 14.4, <sup>3</sup>*J*H,H = 7.1 Hz, 1H), 3.78-3.62 (m, 1H), 3.43 (dq, <sup>2</sup>*J*H,H = 14.3, <sup>3</sup>*J*H,H = 7.1 Hz, 1H), 2.97 (dq, <sup>2</sup>*J*H,H = 14.0, <sup>3</sup>*J*H,H = 7.0 Hz, 1H), 2.73 (d, <sup>3</sup>*J*H,H = 4.3 Hz, 1H), 1.40 (t, <sup>3</sup>*J*H,H = 7.1 Hz, 3H), 1.26 (s, 3H), 0.97 (t, <sup>3</sup>*J*H,H = 7.1Hz, 3H); 13C NMR (126 MHz, CDCl3) *δ*<sup>C</sup> 166.9, 149.4, 143.6 (+), 141.1, 128.9 (+, 2C), 128.6 (+), 128.6 (+, 2C), 128.3 (+), 127.1 (+), 120.9 (+), 116.3 (+), 100.0 (+), 42.7 (+), 42.1 (+), 40.4 (-), 37.5, 33.3 (+), 22.6 (+), 14.9 (+), 12.8 (+); FT IR (KBr, cm−1): 2972, 2929, 1733, 1637, 1479, 1460, 1448, 1433, 1377, 1265, 1220, 1143, 1097, 1070, 952, 846, 796, 775, 763, 723, 702, 624, 598; HRMS (TOF ES): found 348.2076, calculated for C22H26N3O (M+H)<sup>+</sup> 348.2070 (1.7 ppm).

*(+)-(1S,2S,3R)-N,N-Diethyl-2-methyl-3-(methyl(phenyl)amino)-2-phenylcyclopropane-1-carboxamide* (**23ack**). Compound was obtained according to typical procedure B from 62.0 mg (.201 mmol, 1.00 equiv.) of (1*R*,2*S*)-1-bromo-*N*,*N*-diethyl-2-methyl-2 phenylcyclopropane-1-carboxamide (**20ac**), employing *N*-methylaniline (**25k**) (65.0 μL, 0.600 mmol, 3.00 equiv.) as pronucleophile. Chromatographic purification afforded

36.4 mg (0.110 mmol, 55.0%) as yellow oil, R*<sup>f</sup>* 0.22 (hexanes/EtOAc 5:1), dr 3:1 1H NMR (500 MHz, CDCl3) *δ*<sup>H</sup> 7.43–7.12 (m, 7H), 6.95 (d, <sup>3</sup>*J*H,H = 7.9 Hz, 2H), 6.79 (d, <sup>3</sup>*J*H,H = 7.3 Hz, 3H), 3.78 (d, <sup>3</sup>*J*H,H = 4.4 Hz, 1H), 3.68–3.55 (m, 2H), 3.19 (dq, <sup>2</sup>*J*H,H = 14.7, <sup>3</sup>*J*H,H = 7.2 Hz, 1H), 3.11 (s, 3H), 2.79 (dq, <sup>2</sup>*J*H,H = 14.7, <sup>3</sup>*J*H,H = 7.2 Hz, 1H), 1.97 (d, <sup>3</sup>*J*H,H = 4.4 Hz, 1H), 1.62 (s, 3H), 1.17 (t, <sup>3</sup>*J*H,H = 7.1 Hz, 3H), 0.79 (t, <sup>3</sup>*J*H,H = 7.1 Hz, 3H); 13C NMR (126 MHz, CDCl3) *δ*<sup>C</sup> 167.2, 151.0, 141.0, 129.2 (+, 2C), 128.5 (+, 2C), 127.8 (+, 2C), 126.8 (+), 118.1, 114.8 (+, 2C), 48.5 (+), 41.6 (-), 40.4 (+), 39.8 (-), 38.3, 36.9 (+), 21.0 (+), 14.6 (+), 12.6 (+); FT IR (KBr, cm<sup>−</sup>1): 2972, 2929, 1639, 1598, 1500, 1479, 1444, 1433, 1379, 1305, 1220, 1143, 1116, 1029, 950, 904, 698, 611; HRMS (TOF ES): found 337.2281, calculated for C22H29N2O (M+H)<sup>+</sup> 3370.2280 (0.3 ppm). [α] 25D = +33.1◦ (c 0.366, CH2Cl2).

*(+)-(1S,2S,3R)-N,N-Diethyl-3-(ethyl(phenyl)amino)-2-methyl-2-phenylcyclopropane-1-carboxamide* (**23acl**). Compound was obtained according to typical procedure B from 62.0 mg (0.201 mmol, 1.00 equiv.) of (1*R*,2*S*)-1-bromo-*N*,*N*-diethyl-2-methyl-2-phenylcyclopropane-1-carboxamide (**20ac**), employing *N*-ethylaniline (**25l**) (75.0 μL, 0.600 mmol, 3.00 equiv.) as pronucleophile. Chromatographic purification afforded 44.8 mg (0.128 mmol, 64%) as a yellow oil, Rƒ 0.31 (hexanes/EtOAc 5:1), [α] 25D = +11.6◦ (c 0.160, CH2Cl2). dr 13:1. 1H NMR (500 MHz, CDCl3) *δ*<sup>H</sup> 7.51–7.14 (m, 7H), 7.01–6.89 (m, 2H), 6.76 (t, <sup>3</sup>*J*H,H = 7.3 Hz, 1H), 3.84 (d, <sup>3</sup>*J*H,H = 4.6 Hz, 1H), 3.70–3.42 (m, 4H), 3.14 (dq, <sup>2</sup>*J*H,H = 14.3, <sup>3</sup>*J*H,H = 7.1 Hz, 1H), 2.84 (dq, <sup>2</sup>*J*H,H = 13.9, <sup>3</sup>*J*H,H = 7.0 Hz, 1H), 1.95 (d, <sup>3</sup>*J*H,H = 4.6 Hz, 1H), 1.60 (s, 3H), 1.21 (t, <sup>3</sup>*J*H,H = 7.0 Hz, 3H), 1.14 (t, <sup>3</sup>*J*H,H = 7.1 Hz, 3H), 0.76 (t, <sup>3</sup>*J*H,H = 7.1 Hz, 3H); 13C NMR (126 MHz, CDCl3) *δ*<sup>C</sup> 167.3, 149.2, 141.0, 129.2 (+, 2C), 128.4 (+, 2C), 127.6 (+, 2C), 126.7 (+, 2C), 118.0 (+), 115.7 (+), 46.3 (+), 46.2 (-), 41.5 (-), 39.7 (-), 36.9 (+), 14.5 (+), 12.5 (+), 11.2 (+); FT IR (KBr, cm−1): 3085, 2972, 2358, 1637, 1598, 1498, 1458, 1444, 1434, 1377, 1259, 1143, 1080, 831, 752, 696, 613; HRMS (TOF ES): found 350.2358, calculated for C23H30N2O (M+) 350.2358 (0.0 ppm).

*(+)-(1S,2S,3R)-N,N-Diethyl-3-((4-fluorophenyl)(methyl)amino)-2-methyl-2-phenylcyclopropane-1-carboxamide* (**23acm**). Compound was obtained according to typical procedure B from 59.8 mg (0.193 mmol, 1.00 equiv.) of (1*R*,2*S*)-1-bromo-*N*,*N*-diethyl-2-methyl-2-phenylcyclopropane-1-carboxamide (**20ac**), employing 4-fluoro-*N*-methylaniline (**25m**) (72.2 μL, 0.600 mmol, 3.11 equiv.) as pronucleophile. Chromatographic purification afforded 41.6 mg (0.118 mmol, 61%) of the title compound as a yellow oil, R*<sup>f</sup>* 0.25 (hexanes/EtOAc 4:1), [α] 25D = +35.4◦ (c 0.362, CH2Cl2). dr 3:1. 1H NMR (500 MHz, CDCl3) *δ*<sup>H</sup> 7.35–7.27 (m, 4H), 7.21 (ddd, <sup>3</sup>*J*H,F = 5.0 Hz, <sup>3</sup>*J*H,H = 4.5, 1.9 Hz, 1H), 7.00–6.84 (m, 4H), 3.71 (d, <sup>3</sup>*J*H,H = 4.4 Hz, 1H), 3.67–3.55 (m, 2H), 3.18 (dd, <sup>2</sup>*J*H,H = 14.7, <sup>3</sup>*J*H,H = 7.2 Hz, 1H), 3.08 (s, 3H), 2.85 (dd, <sup>2</sup>*J*H,H = 13.6, <sup>3</sup>*J*H,H = 7.0 Hz, 1H), 1.91 (d, <sup>3</sup>*J*H,H = 4.4 Hz, 1H), 1.62 (s, 3H), 1.16 (t, <sup>3</sup>*J*H,H = 7.2 Hz, 3H), 0.79 (t, <sup>3</sup>*J*H,H = 7.1 Hz, 3H); 13C NMR (126 MHz, CDCl3) *δ*<sup>C</sup> 167.1, 156.3 (d, <sup>1</sup>*J*C,F = 236.5 Hz), 147.5 (d, <sup>4</sup>*J*C,F = 1.9 Hz), 140.8, 128.4 (+, 2C), 127.6 (+, 2C), 126.7 (+), 116.0 (d, <sup>2</sup>*J*C,F = 7.4 Hz, +, 2C), 115.4 (d, <sup>3</sup>*J*C,F = 22.0 Hz, +, 2C), 48.8 (+), 41.5 (-), 41.1 (+), 39.7 (-), 38.1 (+), 36.8(+), 20.8 (+), 14.4 (+), 12.5 (+); FT IR (KBr, cm<sup>−</sup>1): 2974, 2873, 1635, 1510, 1479, 1458, 1446, 1379, 1263, 1224, 1143, 1022, 825, 763, 698; HRMS (TOF ES): found 353.2028, calculated for C22H26FN2O (M-H)<sup>+</sup> 353.2029 (0.3 ppm).

*(+)-(1R,2R,3S)-3-(Benzyloxy)-N-(tert-butyl)-2-ethyl-2-phenylcyclopropane-1-carboxamide* (**23baf**). Compound was obtained according to typical procedure B from 72.2 mg (0.223 mmol, 1.00 equiv) of (1*S*,2*R*)-1-bromo-*N*-(*tert*-butyl)-2-ethyl-2-phenylcyclopropane-1-carboxamide (**20ba**), employing benzyl alcohol (**25f**) (64.9 μL, 0.624 mmol, 2.80 equiv.) as pronucleophile. Chromatographic purification afforded 49.0 mg (0.139 mmol, 70%) of the title compound as a colorless solid, mp: 136.2–137.1 ◦C, Rƒ 0.23 (hexanes/EtOAc 9:1), [α] 25D = +50.0◦ (c 0.11, CH2Cl2). dr 39:1. Spectral properties of this material were identical to those reported for the racemic compound [67].

*(-)-(1R,2R,3S)-3-(Allyloxy)-N-(tert-butyl)-2-methyl-2-(p-tolyl)cyclopropane-1 carboxamide* (**23cad**). Compound was obtained according to typical procedure B from 65.0 mg (0.200 mmol, 1.00 equiv.) of (1*S*,2*R*)-1-bromo-*N*-(*tert*-butyl)-2-methyl-2-(*p*-tolyl) cyclopropane-1-carboxamide (**20ca**), employing allyl alcohol (**25e**) (41.0 μL, 0.600 mmol, 3.00 equiv) as pronucleophile. Chromatographic purification afforded 42.0 mg (0.146 mmol, 73%) of the title compound as a colorless solid, mp: 120.6–122.7 ◦C, R*<sup>f</sup>* 0.38 (hexanes/EtOAc 5:1), [α] 25D <sup>=</sup> −21.8◦ (c 0.16, CH2Cl2). dr 50:1. 1H NMR (500 MHz, CDCl3) *<sup>δ</sup>*<sup>H</sup> 7.12 (d, <sup>3</sup>*J*H,H = 8.1 Hz, 2H), 7.08 (d, <sup>3</sup>*J*H,H = 7.9 Hz, 2H), 5.99 (ddt, <sup>3</sup>*J*H,H = 16.2, 10.5, 5.7 Hz, 1H), 5.36 (dd, <sup>3</sup>*J*H,H = 17.2, <sup>2</sup>*J*H,H = 1.6 Hz, 1H), 5.24 (dd, <sup>3</sup>*J*H,H = 10.4, <sup>2</sup>*J*H,H = 1.4 Hz, 1H), 5.08 (br. s, 1H), 4.27–4.10 (m, 2H), 4.07 (d, <sup>3</sup>*J* = 3.3 Hz, 1H), 2.29 (s, 3H), 1.65 (d, <sup>3</sup>*J* = 3.3 Hz, 1H), 1.50 (s, 3H), 1.16 (s, 9H); 13C NMR (126 MHz, CDCl3) *δ*<sup>C</sup> 168.1, 138.3, 136.4, 134.3 (+), 129.3 (+, 2C), 128.5 (+, 2C), 117.7 (-), 72.3 (-), 66.4 (+), 51.1, 37.0 (+), 37.0, 28.8 (+, 3C), 22.0 (+), 21.2 (+); FT IR (KBr, cm<sup>−</sup>1): 3301, 2966, 2923, 1643, 1546, 1515, 1454, 1226, 1145, 985, 925, 817; HRMS (TOF ES): found 300.1967, calculated for C19H26NO2 (M-H)+ 300.1964 (1.0 ppm).

*(+)-(1R,2R,3S)-N-(tert-Butyl)-3-(2-methoxyethoxy)-2-methyl-2-(p-tolyl)cyclopropane-1-carboxamide* (**23cae**). Compound was obtained according to typical procedure B from 62.5 mg (0.193 mmol, 1.00 equiv.) of (1*S*,2*R*)-1-bromo-*N*-(*tert*-butyl)-2-methyl-2-(*p*-tolyl) cyclopropane-1-carboxamide (**20ca**), employing 2-methoxyethanol (**25e**) (47.3 μL, 0.645 mmol, 3.22 equiv.) as pronucleophile. Chromatographic purification afforded 49.5 mg (0.155 mmol, 78%) of the title compound as a colorless solid, mp: 94.9–97.1 ◦C, Rƒ 0.26 (hexanes/EtOAc 1:1), [α] 25D = +32.0◦ (c 0.05, CH2Cl2). dr > 100:1. Spectral properties of this material were identical to those reported for the racemic compound [67].

*(-)-(1R,2R,3S)-3-(Benzyloxy)-N-(tert-butyl)-2-methyl-2-(p-tolyl)cyclopropanecarboxamide* (**23caf**) [67]. Compound was obtained according to typical procedure B from 130 mg (0.401 mmol, 1.00 equiv.) of (1*S*,2*R*)-1-bromo-*N*-(*tert*-butyl)-2-methyl-2-(*p*-tolyl)cyclopropane-1-carboxamide (**20ca**), employing benzyl alcohol (**25f**) (124 μL, 1.20 mmol, 3.00 equiv.) as pronucleophiles. The subsequent chromatographic purification afforded 129 mg (0.367 mmol, 92%) of the title compound as a colorless solid, mp: 139.8–140.6 oC, R*<sup>f</sup>* 0.33 (hexanes/EtOAc 6:1), [α] 25D = –24.5◦ (c 1.10, CH2Cl2). dr 44:1. 1H NMR (500 MHz, CDCl3) *δ*<sup>H</sup> 7.54–7.17 (m, 5H), 7.10 (q, <sup>3</sup>*J*H,H = 8.1 Hz, 4H), 5.03 (br. s, 1H), 4.87–4.53 (m, 2H), 4.12 (d, <sup>3</sup>*J*H,H = 3.3 Hz, 1H), 2.30 (s, 3H), 1.66 (d, <sup>3</sup>*J*H,H = 3.3 Hz, 1H), 1.54 (s, 3H), 1.16 (s, 9H); 13C NMR (126 MHz, CDCl3) *δ*<sup>C</sup> 168.0, 138.3, 137.7, 136.4, 129.3 (+, 2C), 128.6 (+, 2C), 128.5 (+, 2C), 128.3 (+, 2C), 128.0 (+), 73.5 (-), 66.6 (+), 51.1, 37.1 (+), 28.8 (+, 3C), 22.1 (+), 21.2 (+); FT IR (KBr, cm−1): 3308, 3063, 3030, 2966, 2926, 2864, 1643, 1543, 1516, 1454, 1431, 1375, 1364, 1346, 1277, 1226, 1204, 1144, 1099, 987, 817, 750, 734, 698; HRMS (TOF ES): found 374.2098, calculated for C23H29NO2 (M+Na)<sup>+</sup> 374.2096 (0.5 ppm).

*(+)-(1R,2R,3S)-N-(tert-Butyl)-2-methyl-3-(1H-pyrrol-1-yl)-2-(p-tolyl)cyclopropane-1-carboxamide* (**23cag**). Compound was obtained according to typical procedure B from 64.6 mg (0.199 mmol, 1.00 equiv.) of (1*S*,2*R*)-1-bromo-*N*-(*tert*-butyl)-2-methyl-2-(*p*-tolyl) cyclopropane-1-carboxamide (**20ca**), employing pyrrole (**25g**) (42.0 μL, 0.600 mmol, 3.00 equiv.) as pronucleophile. Chromatographic purification afforded 52.0 mg (0.168 mmol, 84%) of the title compound as a colorless solid, mp: 208.0–210.1 oC, R*<sup>f</sup>* 0.31 (hexanes/EtOAc 6:1), [α] 25D = +46.5◦ (c 0.142, CH2Cl2). dr > 99:1. 1H NMR (500 MHz, CDCl3) *δ*<sup>H</sup> 7.22 (d, <sup>3</sup>*J*H,H = 8.0 Hz, 2H), 7.14 (d, <sup>3</sup>*J*H,H = 7.9 Hz, 2H), 6.77 (t, <sup>3</sup>*J*H,H = 2.1 Hz, 2H), 6.19 (t, <sup>3</sup>*J*H,H = 2.1 Hz, 2H), 5.35 (br. s, 1H), 4.31 (d, <sup>3</sup>*J*H,H = 4.2 Hz, 1H), 2.32 (s, 3H), 2.17 (d, <sup>3</sup>*J*H,H = 4.2 Hz, 1H), 1.26 (s, 3H), 1.22 (s, 9H); 13C NMR (126 MHz, CDCl3) *<sup>δ</sup>*<sup>C</sup> 166.9, 137.7, 137.0, 129.5 (+, 2C), 128.4 (+, 2C), 121.6 (+, 2C), 108.6 (+, 2C), 51.6, 45.0 (+), 37.1, 36.7 (+), 28.8 (+, 3C), 23.1 (+), 21.3 (+); FT IR (KBr, cm−1): 3319, 2966, 2925, 1645, 1546, 1539, 1492, 1454, 1361, 1265, 1224, 1093, 1066, 981, 817, 721, 700; HRMS (TOF ES): found 309.1974, calculated for C20H25N2O (M-H)+ 309.1967 (2.3 ppm).

*(+)-(1R,2R,3S)-N-(tert-Butyl)-2-methyl-3-(1H-pyrazol-1-yl)-2-(p-tolyl)cyclopropane-1-carboxamide* (**23cah**): Compound was obtained according to typical procedure B from 65.0 mg (0.200 mmol, 1.00 equiv.) of (1*S*,2*R*)-1-bromo-*N*-(*tert*-butyl)-2-methyl-2-(*p*-tolyl) cyclopropane-1-carboxamide (**20ca**), employing pyrazole (**25h**) (41.0 mg, 0.600 mmol, 3.00 equiv) as pronucleophiles. The subsequent chromatographic purification afforded 47.0 mg (0.158 mmol, 79%) of the title compound as a colorless solid, mp: 147.9–148.5 ◦C, R*<sup>f</sup>* 0.35 (CH2Cl2/MeOH 20:1), [α] 25D = +40.6◦ (c 0.35, CH2Cl2). dr 15:1. 1H NMR (500 MHz, CDCl3) *δ*<sup>H</sup> 7.51 (d, <sup>3</sup>*J*H,H = 2.1 Hz, 1H), 7.47 (d, <sup>3</sup>*J*H,H = 1.2 Hz, 1H), 7.17 (d, <sup>3</sup>*J*H,H = 7.9 Hz, 2H), 7.05 (d, <sup>3</sup>*J*H,H = 7.9 Hz, 2H), 6.25 (t, <sup>3</sup>*J*H,H = 1.9 Hz, 1H), 5.69 (br. s, 1H), 4.46 (d, <sup>3</sup>*J*H,H = 4.0 Hz, 1H), 2.61–2.45 (m, 1H), 2.24 (s, 3H), 1.16 (s, 9H), 1.12 (s, 3H); 13C NMR (126 MHz, CDCl3) *δ*<sup>C</sup> 166.5, 139.4 (+), 137.6, 136.8, 130.6 (+), 129.4 (+, 2C), 128.4 (+, 2C), 106.2 (+), 51.6, 47.1 (+), 37.4, 35.8 (+), 28.8 (+, 3C), 22.7 (+), 21.3 (+); FT IR (KBr, cm<sup>−</sup>1): 3306, 2964, 2925, 1649, 1544, 1452, 1392, 1274, 1224, 1089, 1047, 820, 752, 615; HRMS (TOF ES): found 312.2081, calculated for C19H26N3O (M+H)<sup>+</sup> 312.2076 (1.6 ppm).

*(-)-(1R,2R,3S)-3-(Allyloxy)-N-(tert-butyl)-2-methyl-2-(naphthalen-2-yl)cyclopropane-1-carboxamide* (**23dad**). Compound was obtained according to typical procedure B from 69.9 mg (0.194 mmol, 1.00 equiv.) of (1*S*,2*R*)-1-bromo-*N*-(*tert*-butyl)-2-methyl-2-(naphthalen-2-yl)cyclopropane-1-carboxamide (**20da**), employing allyl alcohol (**25d**) (40.8 μL, 0.600 mmol, 3.09 equiv.) as pronucleophile. Chromatographic purification afforded 57.9 mg (0.172 mmol, 88%) of the title compound as a colorless solid, mp: 122.2–125.1 ◦C, R*<sup>f</sup>* 0.26 (hexanes/EtOAc 4:1), [α] 25D <sup>=</sup> −7.87◦ (c 0.178, CH2Cl2). dr > 99:1. 1H NMR (500 MHz, CDCl3) *<sup>δ</sup>*<sup>H</sup> 7.85–7.72 (m, 3H), 7.69 (s, 1H), 7.50–7.36 (m, 2H), 7.35 (dd, <sup>3</sup>*J*H,H = 8.4, <sup>4</sup>*J*H,H = 1.7 Hz, 1H), 6.04 (ddt, <sup>3</sup>*J*H,H = 17.2, 10.5, 5.7 Hz, 1H), 5.41 (dd, <sup>3</sup>*J*H,H = 17.2, <sup>2</sup>*J*H,H = 1.6 Hz, 1H), 5.27 (dd, <sup>3</sup>*J*H,H = 10.4, <sup>2</sup>*J*H,H = 1.4 Hz, 1H), 5.17 (br. s, 1H), 4.34–4.05 (m, 2H), 4.22 (d, <sup>3</sup>*J*H,H = 3.3 Hz, 1H), 1.75 (d, <sup>3</sup>*J*H,H = 3.3 Hz, 1H), 1.59 (s, 3H), 1.13 (s, 9H); 13C NMR (126 MHz, CDCl3) *δ*<sup>C</sup> 167.9, 139.0, 134.3 (+), 133.6, 132.6, 128.2 (+), 127.8 (+), 127.8 (+), 127.3 (+), 127.0 (+), 126.1 (+), 125.7 (+), 117.8 (-), 72.4 (-), 66.5 (+), 51.2, 37.5, 37.1 (+), 28.8 (+, 3C), 22.0 (+); FT IR (KBr, cm<sup>−</sup>1): 3319, 2966, 2925, 1643, 1542, 1454, 1361, 1269, 1226, 1147, 1128, 1087, 1062, 1041, 985, 923, 856, 817, 744, 667; HRMS (TOF ES): found 338.2119, calculated for C22H28NO2 (M+H)<sup>+</sup> 338.2120 (0.3 ppm).

*(-)-(1R,2R,3S)-N-(tert-Butyl)-3-(2-methoxyethoxy)-2-methyl-2-(naphthalen-2-yl) cyclopropane-1-carboxamide* (**23dae**). Compound was obtained according to typical procedure B from 71.8 mg (0.199 mmol, 1.00 equiv.) of (1*S*,2*R*)-1-bromo-*N*-(*tert*-butyl)-2-methyl-2- (naphthalen-2-yl)cyclopropane-1-carboxamide (**20da**), employing 2-methoxyethanol (**25e**) (47.3 μL, 0.600 mmol, 3.02 equiv.) as pronucleophile. Chromatographic purification afforded 53.8 mg (0.151 mmol, 76%) of the title compound as a colorless solid, mp: 143.2–144.2 ◦C, R*<sup>f</sup>* 0.25 (hexanes/EtOAc 2:1), [α] 25D <sup>=</sup> −6.1◦ (c 0.214, CH2Cl2). dr > 99:1. 1H NMR (500 MHz, CDCl3) *δ*<sup>H</sup> 7.86–7.65 (m, 4H), 7.54–7.32 (m, 3H), 5.19 (br. s, 1H), 4.23 (d, <sup>3</sup>*J*H,H = 3.3 Hz, 1H), 3.96–3.77 (m, 2H), 3.73–3.60 (m, 2H), 3.44 (s, 3H), 2.17 (s, 3H), 1.76 (d, <sup>3</sup>*J*H,H = 3.3 Hz, 1H), 1.12 (s, 9H); 13C NMR (126 MHz, CDCl3) *δ*<sup>C</sup> 167.9, 139.0, 133.6, 132.6, 128.2 (+), 127.8 (+), 127.3 (+), 127.0 (+), 126.0 (+), 125.7 (+), 71.9 (-), 70.5 (-), 67.0 (+), 59.3 (+), 51.2, 37.6, 37.0 (+), 31.1 (+), 28.8 (+, 3C), 21.9 (+); FT IR (KBr, cm−1): 3323, 2966, 2871, 1645, 1541, 1454, 1390, 1363, 1269, 1226, 1151, 1124, 956, 856, 817, 742, 667; HRMS (TOF ES): found 356.2225, calculated for C22H30NO3 (M+H) 356.2226 (0.3 ppm).

*(+)-(1R,2R,3S)-N-(tert-Butyl)-2-methyl-2-(naphthalen-2-yl)-3-(1H-pyrrol-1-yl) cyclopropane-1-carboxamide* (**23dag**). Compound was obtained according to typical procedure B from 71.4 mg (0.198 mmol, 1.00 equiv.) of (1*S*,2*R*)-1-bromo-*N*-(*tert*-butyl)-2-methyl-2-(naphthalen-2-yl)cyclopropane-1-carboxamide (**20da**), employing pyrrole (**25g**) (42.0 μL, 0.606 mmol, 3.06 equiv.) as pronucleophile. Chromatographic purification afforded 51.9 mg (0.149 mmol, 75%) of the title compound as a colorless solid, mp: 181.4–183.2 oC, R*<sup>f</sup>* 0.23 (hexanes/EtOAc 6:1), [α] 25D = +15.6◦ (c 0.096 CH2Cl2). dr 81:1. 1H NMR (500 MHz, CDCl3) *δ*<sup>H</sup> 8.01–7.67 (m, 4H), 7.57–7.35 (m, 3H), 6.85 (t, <sup>3</sup>*J*H,H = 2.1 Hz, 2H), 6.23 (t, <sup>3</sup>*J*H,H = 2.1 Hz, 2H), 5.44 (br., s, 1H), 4.46 (d, <sup>3</sup>*J*H,H = 4.1 Hz, 1H), 2.28 (d, <sup>3</sup>*J*H,H = 4.2 Hz, 1H), 1.36 (s, H), 1.19 (s, 9H); 13C NMR (126 MHz, CDCl3) *δ*<sup>C</sup> 166.7, 138.3, 133.6, 132.7, 128.5 (+), 127.8 (+), 127.8 (+), 127.3 (+), 126.7 (+), 126.3 (+), 126.0 (+), 121.7 (+, 2C), 108.7 (+, 2C), 51.7, 45.2 (+), 37.7, 36.8 (+), 28.8 (+, 3C), 23.0 (+); FT IR (KBr, cm−1): 3305, 2968, 1650, 1548, 1492, 1454, 1392, 1265, 1224, 1132, 1091, 1064, 981, 854, 817, 721, 680, 657; HRMS (TOF ES): found 346.2047, calculated for C23H26N2O (M+) 346.2045 (0.6 ppm).

*(1R\*,2R\*,3S\*)-N-(tert-butyl)-2-ethyl-2-phenyl-3-(1H-pyrrol-1-yl)cyclopropane-1 carboxamide* (**23aag**). This compound was obtained according to procedure B, employing pyrrole (42 μL, 0.60 mmol, 3.0 equiv.) as pronucleophile. The reaction mixture was stirred overnight at 40 ◦C, and GC analysis showed incomplete conversion (75% based on starting material) and dr 17:1; after heating at 80 ◦C for 30 min, the reaction was complete. The

subsequent chromatographic purification afforded 35 mg (0.114 mmol, 57%) of the title compound as a white solid, mp: 177.5–120.0 oC, R*<sup>f</sup>* 0.29 (hexanes/EtOAc 6:1), dr 14:1. 1H NMR (500 MHz, CDCl3) *<sup>δ</sup>*<sup>H</sup> 7.44–7.07 (m, 5H), 6.72 (t, <sup>3</sup>*J*H,H = 2.1 Hz, 2H), 6.12 (t, <sup>3</sup>*J*H,H = 2.1 Hz, 2H), 5.28 (br. s, 1H), 4.25 (d, <sup>3</sup>*J*H,H = 4.3 Hz, 1H), 2.12 (d, <sup>3</sup>*J*H,H = 4.3 Hz, 1H), 1.45–1.32 (m, 2H), 1.16 (s, 9H), 0.71 (t, *J*H,H = 7.4 Hz, 3H); 13C NMR (126 MHz, CDCl3) *δ*<sup>C</sup> 166.9, 138.6, 129.7 (+, 2C), 128.4 (+, 2C), 127.4 (+), 121.7 (+, 2C), 108.6 (+, 2C), 51.6, 46.3 (+), 43.0, 35.1 (+), 28.8 (+, 3C), 28.5 (-), 11.3 (+); FT IR (KBr, cm−1): 3317, 3060, 2968, 2931, 1647, 1545, 1492, 1446, 1263, 1224, 721, 698; HRMS (TOF ES): found 309.1968, calculated for C20H25N2ONa (M-H) 342.2045 (0.6 ppm).

*(+)-(1R,2R,3S)-N-(tert-Butyl)-3-(ethyl(phenyl)amino)-2-methyl-2-(naphthalen-2-yl) cyclopropane-1-carboxamide* (**23dal**). Compound was obtained according to typical procedure B from 39.1 mg (0.109 mmol, 1.00 equiv.) of (1*S*,2*R*)-1-bromo-*N*-(*tert*-butyl)-2-methyl-2-(naphthalen-2-yl)cyclopropane-1-carboxamide (**20da**), employing *N*-ethylaniline (**25l**) (40 μL, 0.318 mmol, 2.92 equiv.) as pronucleophile. Chromatographic purification afforded 29.8 mg (0.074 mmol, 68%) of the title compound as a colorless solid, m.p. 132.3–135.1 ◦C, R*<sup>f</sup>* 0.31 (hexanes/EtOAc 6:1), [α] 25D = +10.8◦ (c 0.074, CH2Cl2). dr > 99:1. 1H NMR (500 MHz, CDCl3) *<sup>δ</sup>*<sup>H</sup> 7.97–7.66 (m, 4H), 7.55–7.39 (m, 3H), 7.27–7.19 (m, 2H), 7.06–6.93 (m, 2H), 6.80 (t, <sup>3</sup>*J*H,H = 7.3 Hz, 1H), 5.18 (br. s, 1H), 3.71 (d, <sup>3</sup>*J*H,H = 4.4 Hz, 1H), 3.77–3.64 (m, 1H), 3.61–3.48 (m, 1H), 1.73 (d, <sup>3</sup>*J*H,H = 4.4 Hz, 1H), 1.61 (s, 3H), 1.25 (t, <sup>3</sup>*J*H,H = 7.0 Hz, 3H), 1.10 (s, 9H); 13C NMR (126 MHz, CDCl3) *<sup>δ</sup>*<sup>C</sup> 167.8, 149.2, 139.2, 133.6, 132.5, 129.2 (+, 2C), 128.3 (+), 127.9 (+), 127.8 (+), 126.9 (+), 126.8 (+), 126.2 (+), 125.8 (+), 118.3 (+), 116.0 (+), 51.3, 46.8 (+), 46.4 (-), 39.2 (+), 39.0, 28.8 (+, 3C), 21.9 (+), 11.2 (+); FT IR (KBr, cm−1): 2968, 2358, 1645, 1595, 1531, 1498, 1454, 1366, 1255, 1188, 817, 742, 692; HRMS (TOF ES): found 399.2438, calculated for C27H31N2O (M-H)+ 399.2436 (0.5 ppm).
