Rhodium- and Non-Metal-Catalyzed Approaches for the Conversion of Isoxazol-5-ones to 2,3-Dihydro-6H-1,3- Oxazin-6-ones

Transcription

1 Supporting Information Rhodium- and Non-Metal-Catalyzed Approaches for the Conversion of Isoxazol-5-ones to 2,3-Dihydro-6H-1,3- Oxazin-6-ones Igor D. Jurberg a,b,* and Huw M. L. Davies a,* a Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia, 30322, United States. hmdavie@emory.edu b Institute of Chemistry, State University of Campinas, Rua Monteiro Lobato 270, Campinas, São Paulo, , Brazil. idjurberg@iqm.unicamp.br

2 Table of contents: 1. General Considerations S3 2. Preparation of Starting Materials S4 2.1 Isoxazol-5-ones S4 General Procedure A S4 2.2 Diazocompounds S7 3. Preparation of 2,3-dihydro-6H-1,3-oxazin-6-ones S Full Optimization Table S Brief Screening for Asymmetric Version S12 General Procedure B S13 General Procedure C S13 General Procedure D S13 4. Preparation of 2-aryl-2-tosyloxy esters S23 5. NMR Spectra S Isoxazol-5-ones S Diazocompounds S ,3-dihydro-6H-1,3-oxazin-6-ones S aryl-2-tosyloxy esters S93 S2

3 1. General Considerations All reactions were conducted in oven-dried glassware under an inert atmosphere of dry argon. All reagents were used as received from commercial suppliers, unless otherwise stated. All solvents were purchased from Sigma Aldrich, dried over calcium hydride, and freshly distilled prior to use in synthesis. Proton ( 1 H) NMR spectra were recorded at 400 or 500 MHz on a Varian- 400 or an Inova-500 spectrometer, respectively. Carbon-13 ( 13 C) NMR spectra were recorded at 100 or 125 MHz on a Varian-400 or an Inova-500 spectrometer, respectively. NMR spectra were recorded in deuterated chloroform (CDCl 3 ) solutions, with residual chloroform (δ 7.26 ppm for 1 H NMR and δ 77.0 ppm for 13 C NMR) as the internal standard, and were reported in parts per million (ppm). Abbreviations for signal couplings are as follows: s, singlet; d, doublet; t, triplet; q, quartet; quin, quintet; sex, sextet; sep, septet; and m, multiplet. Coupling constants were taken from the spectra directly and are uncorrected. Infrared (IR) Spectra were collected on a Nicolet Impact Series 10 FT-IR. Mass spectrometric determinations were carried out on a Thermo Finnigan LTQ- FTMS spectrometer with nano-spray ionization (NSI). Analytical thin layer chromatography (TLC) was performed on silica gel plates using ultraviolet (UV) light or stained with either KMnO 4 or phosphomolybdic acid (PMA). Flash column chromatography was performed with silica gel 60 Å ( mesh). S3

4 2. Preparation of Starting Materials 2.1 Isoxazol-5-ones General Prodecure A: 1 Under air, at room temperature, HCl.H 2 NOH (1.5 equiv.) and NaOAc (1.5 equiv.) are dissolved in absolute EtOH (0.5M). Then, the -ketoester (1 equiv.) is added. The reaction mixture is heated to reflux (78 o C). Upon completion (as judged by TLC analysis), the reaction mixture is concentrated under reduced pressure to remove the EtOH. The resulting crude is dissolved in water, and extracted with AcOEt (3x). The combined organic phases are dried (MgSO 4 ) and concentrated again under reduced pressure. Purification by flash column chromatography affords the corresponding isoxazol-5-one 1 in the stated yields. 3-butylisoxazol-5(4H)-one (1a) General Procedure A is employed using methyl 3- oxoheptanoate (3.16 g, 20 mmol), HCl.H 2 NOH (2.09 g, 30 mmol), NaOAc (2.46 g, 30 mmol) in EtOH (40 ml). Purification by flash column chromatography (SiO 2, gradient: Hex- 9:1 Hex:AcOEt 8:2 Hex:AcOEt 7:3 Hex:AcOEt 1:1 Hex:AcOEt) affords the title compound as a pale yellow oil (1.8 g, 64%). 1 H (CDCl 3, 400 MHz) : 3.37 (s, 2H), 2.45 (t, J = 7.6 Hz, 2H), (m, 2H), (m, 2H), 0.93 (t, J = 7.2 Hz, 3H). 13 C (CDCl 3, 100 MHz) : 175.3, 167.0, 35.8, 28.8, 27.9, 22.2, IR (ATR, cm -1 ): 2960 (m), 2933 (m), 2873 (w), 1793 (s), 1612 (w), 1467 (w), 1370 (w), 1165 (s). HRMS (NSI+): Calcd. for [C 7 H 11 NO 2 +H] + : Found: N. M. R. Capreti, I. D. Jurberg, Org. Lett. 2015, 17, Bess, E. N.; Guptill, D. M.; Davies, H. M.; Sigman, M. S.; Chem. Sci. 2015, 6, S4

5 3-isopropylisoxazol-5(4H)-one(1b) General Procedure A is employed using methyl 4-methyl-3- oxopentanoate (5.76 g, 40 mmol), HCl.H 2 NOH (4.18 g, 60 mmol), NaOAc (4.92 g, 60 mmol) in EtOH (80 ml). Purification by flash column chromatography (SiO 2, DCM) affords the title compound as an orange oil (3.95 g, 78%). 1 H (CDCl 3, 500 MHz) : 3.38 (s, 2H), 2.80 (hept, J =7.0 Hz 1H), 1.24 (d, J = 7.0 Hz, 6H). 13 C (CDCl 3, 125 MHz) : 175.3, 171.2, 34.0, 29.5, IR (ATR, cm -1 ): 2973 (w), 2934 (w), 2880 (w), 1794 (s), 1609 (w), 1470 (w), 1370 (w), 1172 (m). HRMS (NSI+): Calcd for [C 6 H 9 NO 2 +H] + : Found: methylisoxazol-5(4H)-one (1c) General Procedure A is employed using methyl 3-oxobutanoate (2.32 g, 20 mmol), HCl.H 2 NOH (2.09 g, 30 mmol), NaOAc (2.46 g, 30 mmol) in EtOH (40 ml). Purification by flash column chromatography (SiO 2, DCM) affords the title compound as an orange oil (1.1 g, 56%). 1 H (CDCl 3, 400 MHz) : 3.38 (s, 2H), 2.14 (s, 3H). 13 C (CDCl 3, 100 MHz) : 175.2, 163.4, 37.0, IR (ATR, cm -1 ): 2968 (w), 1929 (w), 1792 (s), 1432 (w), 1393 (w), 1374 (m), 1341 (w), 1201 (m), 1166 (s), 1034 (w), 1000 (w). HRMS (NSI+): Calcd. for [C 4 H 5 NO 2 +H] + : Found: ethyl-3-methylisoxazol-5(4H)-one (1d) General Procedure A is employed using ethyl 2-ethyl-3-oxobutanoate (90%, 3.5g, 20 mmol), HCl.H 2 NOH (2.09 g, 30 mmol), NaOAc (2.46 g, 30 mmol) in EtOH (40 ml). Purification by flash column chromatography (SiO 2, gradient: Hex 8:2 Hex:AcOEt 1:1 Hex:AcOEt) affords the title compound as an yellow oil (2.52 g, 99%). 1 H (CDCl 3, 500 MHz) : 3.30 (t, J = 6.0 Hz, 0.87 H), 2.24 (q, J = 7.5 Hz, 0.26H), 2.15 (s, 0.39H), 2.10 (s, 2.61H), (m, 0.87H), (m, 0.87H), 1.10 (t, J = 7.5 Hz, 0.39H), 0.96 (t, J = 8.0 Hz, 2.61 H). S5

6 13 C (CDCl 3, 125 MHz) (only major tautomer described): 178.0, 166.2, 48.0, 20.6, 13.5, 9.6. IR (ATR, cm -1 ): 3202 (br w), 2973 (w), 2938 (w), 2880 (w), 1797 (s), 1692 (s), 1617 (s), 1459 (m), 1431 (m), 1390 (m), 1329 (w), 1211 (w). HRMS (NSI+): Calcd. for [C 6 H 9 NO 2 +H] + : Found: ,5,6,7-tetrahydrobenzo[c]isoxazol-3(3aH)-one (1e) General Procedure A is employed using ethyl 2- oxocyclohexane-1-carboxylate (1.7g, 10 mmol), HCl.H 2 NOH (1.05 g, 15 mmol), NaOAc (1.23 g, 15 mmol) in EtOH (20 ml). Purification by flash column chromatography (SiO 2, gradient: Hex 8:2 Hex:AcOEt 1:1 Hex:AcOEt) affords the title compound as a pale yellow oil (1.4 g, 100%). 1 H (CDCl 3, 500 MHz) : (m, 1H), (m, 1H), (m, 1H), (m, 0.5 Hz), (m, 1.5H), (m, 1H), (m, 1H), (m, 0.5H), (m, 0.5H), (m, 3H). 13 C (CDCl 3, 125 MHz) (only major tautomer described) : 177.7, 169.4, 44.0, 28.6, 26.6, 26.2, IR (ATR, cm -1 ): 3172 (br w), 2941 (w), 2859 (w), 2782 (w), 1789 (w), 1697 (s), 1612 (s), 1445 (m), 1424 (m), 1355 (m), 1245 (w). HRMS (NSI+): Calcd for [C 7 H 9 NO 2 +H] + : Found: a,4,5,6,7,8-hexahydro-3H-cyclohepta[c]isoxazol-3-one (1f) General Procedure A is employed using methyl 2- oxocycloheptane-1-carboxylate (1.7g, 10 mmol), HCl.H 2 NOH (1.05 g, 15 mmol), NaOAc (1.23 g, 15 mmol) in EtOH (20 ml). Purification by flash column chromatography (SiO 2, DCM) affords the title compound as a yellow solid (1.49 g, 97%). 1 H (CDCl 3, 500 MHz) : 3.40 (dd, J = 5.0 Hz, J = 9.0 Hz, 1H), (m, 2H), 2.54 (dd, J = 5.5 Hz, J = 6.0 Hz, 2H), 2.37 (dd, J = 5.5 Hz, J = 6.0 Hz, 2H), (m, 1H), (m, 9H), (m, 4H). S6

7 13 C (CDCl 3, 125 MHz) : 178.5, 173.8, 171.4, 167.3, 104.2, 48.0, 30.9, 29.7, 28.6, 28.5, 28.3, 27.7, 27.6, 26.1, 25.7, IR (ATR, cm -1 ): 2924 (w), 2849 (w), 2764 (w), 1672 (s), 1594 (s), 1575 (s), 1441 (m), 1392 (w), 1366 (w), 1272 (w). HRMS (NSI+): Calcd. for [C 8 H 11 NO 2 +H] + : Found: Diazocompounds ethyl 2-(4-bromophenyl)-2-diazoacetate (2a) Prepared according to the literature 2 1 H (CDCl 3, 400MHz) : 7.47 (d, J = 8.8 Hz, 2H), 7.35 (d, J = 8.8 Hz, 2H), 4.31 (q, J = 7.0 Hz, 2H), 1.32 (t, J = 7.0 Hz, 3H). 13 C (CDCl 3, 100MHz) : 164.8, 132.0, 125.3, 124.8, 119.2, 61.1, IR (ATR, cm -1 ): 2985 (w), 2911 (w), 2088 (s), 1719 (m), 1693 (s), 1584 (w), 1487 (s), 1452 (w), 1388 (m), 1369 (s), 1337 (s), 1302 (m), 1273 (s), 1238 (s). HRMS (NSI+): Calcd. for [C 10 H 9 BrN 2 O 2 +H] + : Found: ethyl 2-diazo-2-phenylacetate (2b) Prepared according to the literature. 3 1 H (CDCl 3, 500 MHz) : (m, 2H), (m, 2H), (m, 1H), 4.34 (q, J = 7.3 Hz, 2H), 1.35 (t, J = 7.3 Hz, 3H). 13 C (CDCl 3, 125MHz) : 165.2, 128.9, 125.7, 125.6, 124.0, 61.0, IR (ATR, cm -1 ): 2981 (w), 2080 (s), 1698 (s), 1598 (w), 1575 (w), 1498 (m), 1464 (w), 1449 (w), 1370 (m), 1337 (m), 1286 (w), 1243 (s). HRMS (NSI+): Calcd. for [C 10 H 10 N 2 O 2 +H+CH 3 CN-N 2 ] + : Found: Bess, E. N.; Guptill, D. M.; Davies, H. M.; Sigman, M. S.; Chem. Sci. 2015, 6, Davis, O. A.; Croft, R. A.; Bull, J. A.; Chem. Commun. 2015, 51, S7

8 isopropyl 2-diazo-2-phenylacetate (2c) Prepared according to the literature. 2 1 H (CDCl 3, 500MHz) : (m, 2H), (m, 2H), (m, 1H), 5.22 (hept, J = 6.3 Hz, 1H), 1.33 (d, J = 6.3 Hz, 6H). 13 C (CDCl 3, 125 MHz) : 164.8, 128.9, 125.8, 125.7, 123.9, 68.7, IR (ATR, cm -1 ): 2980 (w), 2077 (s), 1695 (s), 1598 (w), 1498 (m), 1466 (w), 1450 (w), 1386 (w), 1362 (m), 1327 (m), 1286 (w), 1243 (s). HRMS (NSI+): Calcd. for [C 11 H 12 N 2 O 2 +H+CH 3 CN-N 2 ] + : Found: tert-butyl 2-diazo-2-phenylacetate (2d) Prepared according to the literature. 4 1 H (CDCl 3, 500 MHz) : 7.47 (d, J = 7.5 Hz, 2H), 7.37 (t, J = 7.5 Hz, 2H), 7.16 (t, J = 7.5 Hz, 1H), 1.56 (s, 9H). 13 C (CDCl 3, 125 MHz) : 164.6, 128.8, 126.1, 125.5, 124.0, 82.0, IR (ATR, cm -1 ): 2978 (w), 2078 (s), 1696 (s), 1598 (w), 1498 (m), 1450 (w), 1368 (m), 1349 (m), 1287 (w), 1245 (s), 1139 (s). HRMS (NSI+): Calcd. for [C 12 H 14 N 2 O 2 +H] + : Found: (triisopropylsilyl)ethyl 2-diazo-2-phenylacetate (2e) Prepared according to the literature. 5 1 H (CDCl 3, 500 MHz) : 7.49 (d, J = 7.5 Hz, 2H), 7.39 (t, J = 7.5 Hz, 2H), 7.18 (t, J = 7.5 Hz, 1H), (m, 2H), (m, 2H), 1.07 (s, 21H). 13 C (CDCl 3, 125 MHz) : 165.4, 128.9, (x2), 124.0, 63.5, 18.7, 11.2, IR (ATR, cm -1 ): 2941 (w), 2890 (w), 2865 (w), 2080 (s), 1700 (s), 1599 (w), 1498 (m), 1462 (m), 1380 (w), 1345 (w), 1332 (w), 1285 (w), 1244 (s), 1150 (s). HRMS (NSI-): Calcd. for [C 19 H 30 N 2 O 2 Si-H] - : Found: Lee, S. I.; Hwang, G.-S.; Ryu, D. H.; J. Am. Chem. Soc. 2013, 135, Guptill, D. M.; Cohen, C. M.; Davies, H. M. L.; Org. Lett. 2013, 15, S8

9 methyl 2-([1,1'-biphenyl]-4-yl)-2-diazoacetate (2f) Prepared according to the literature. 6 1 H (CDCl 3, 500 MHz) : 7.64 (d, J = 8.5 Hz, 2H), (m, 2H), 7.56 (d, J = 8.5 Hz, 2H), 7.45 (t, J = 7.5 Hz, 2H), (m, 1H), 3.90 (s, 3H). 13 C (CDCl 3, 125MHz) : 165.6, 140.3, 138.6, 128.8, 127.6, 127.4, 126.9, (2x), IR (ATR, cm -1 ): 3032 (w), 2953 (w), 2842 (w), 2091 (s), 1695 (s), 1600 (w), 1532 (w), 1487 (m), 1450 (w), 1434 (m), 1411 (w), 1353 (m), 1281 (w), 1269 (m), 1239 (s). HRMS (NSI+): Calcd. for [C 15 H 12 N 2 O 2 +H] + : Found: ,2,2-trichloroethyl 2-(4-(tert-butyl)phenyl)-2-diazoacetate (2g) Prepared according to the literature. 2 1 H (CDCl 3, 500MHz) : (m, 4H), 4.92 (s, 2H), 1.33 (s, 9H). 13 C (CDCl 3, 125MHz) : 163.6, 149.6, 126.1, 124.0, 121.3, 95.1, 73.8, 34.5, IR (ATR, cm -1 ): 2962 (w), 2869 (w), 2089 (s), 1713 (s), 1516 (w), 1373 (w), 1340 (w), 1288 (w), 1268 (w), 1241 (s), 1204 (w). HRMS (NSI+): Calcd. for [C 14 H 15 Cl 3 N 2 O 2 +H] + : Found: methyl 2-diazo-2-(3,4-dichlorophenyl)acetate (2h) Prepared according to the literature. 2 1 H (CDCl 3, 500 MHz) : 7.64 (d, J = 2.5 Hz, 1H), 7.43 (d, J = 8.5 Hz, 1H), 7.29 (dd, J = 2.5 Hz, J = 8.5 Hz, 1H), 3.88 (s, 3H). 13 C (CDCl 3, 125 MHz) : 164.8, 133.2, 130.7, 129.4, 126.0, 125.3, 122.6, IR (ATR, cm -1 ): 3099 (w), 1956 (w), 2094 (s), 1690 (s), 1588 (w), 1550 (w), 1481 (m), 1462 (m), 1436 (s), 1368 (w), 1352 (s), 1281 (m), 1260 (m), 1243 (s), 1192 (s). HRMS (NSI+): Calcd. for [C 9 H 6 Cl 2 N 2 O 2 +H+CH 3 CN-N 2 ] + : Found: Qu, Z.; Shi, W.; Wang, J.; J. Org. Chem. 2001, 66, S9

10 tert-butyl 2-diazo-2-(naphthalen-2-yl)acetate (2i) Prepared according to the literature. 7 1 H (CDCl 3, 500 MHz) : 8.0 (d, J = 1.5 Hz, 1H), 7.84 (d, J = 8.5 Hz, 1H), (m, 2H), 7.51 (dd, J = 1.5 Hz, J = 8.5 Hz, 1H), (m, 2H), 1.59 (s, 9H). 13 C (CDCl 3, 125 MHz) : 164.7, 133.6, 131.3, 128.5, (x2), 126.5, 125.6, 123.3, 122.5, 121.9, 82.2, IR (ATR, cm -1 ): 3065 (w), 2975 (w), 2081 (s), 1754 (m), 1690 (s), 1627 (w), 1600 (w), 1508 (w), 1474 (w), 1455 (w), 1389 (m), 1366 (m), 1330 (m), 1292 (w), 1247 (s). HRMS (NSI+): Calcd. for [C 16 H 16 N 2 O 2 +H] + : Found: (trimethylsilyl)methyl 2-(4-bromophenyl)-2-diazoacetate (2j) Prepared according to the literature. 6 1 H (CDCl 3, 500 MHz) : 7.50 (d, J = 7.5 Hz, 2H), 7.37 (d, J = 7.5 Hz, 2H), 3.94 (s, 2H), 0.11 (s, 9H). 13 C (CDCl 3, 125 MHz) : 165.6, 132.0, 125.2, 124.9, 119.2, 58.3, 3.2. IR (ATR, cm -1 ): 2956 (w), 2083 (s), 1817 (w), 1702 (s), 1588 (w), 1490 (s), 1406 (w), 1348 (s), 1310 (w), 1287 (m), 1249 (s), 1234 (s). HRMS (NSI+): Calcd. for [C 12 H 15 BrN 2 O 2 Si+H] + : Found: (triisopropylsilyl)ethyl 2-diazo-2-(3,4-dimethoxyphenyl)acetate (2k) Prepared according to the literature. 6 1 H (CDCl 3, 500 MHz) : 7.20 (s, 1H), 6.89 (d, J = 2.0 Hz, 2H), (m, 2H), 3.91 (s, 3H), 3.88 (s, 3H), (m, 2H), 1.07 (s, 21H). 13 C (CDCl 3, 125 MHz) : 165.9, 149.4, 147.3, 117.6, 116.5, 111.6, 108.4, 63.4, 56.0, 55.9, 18.7, 11.1, IR (ATR, cm -1 ): 2994 (w), 2940 (w), 2865 (w), 2078 (s), 1694 (s), 1604 (w), 1582 (w), 1520 (w), 1460 (m), 1446 (m), 1418 (w), 1368 (w), 1316 (m), 1300 (m), 1251 (s). HRMS (NSI+): Calcd. for [C 21 H 34 N 2 O 4 Si+Na] + : Found: Wang, H.; Guptill, D. M.; Varela-Alvarez, A.; Musaev, D. G.; Davies, H. M. L.; Chem. Sci. 2013, 4, S10

11 3. Preparation of 2,3-dihydro-6H-1,3-oxazin-6-ones 3.1 Full Optimization Table entry [Rh] (x mol%) y solvent T time yield (%) a 1 Rh(PPh 3 ) 3 Cl (2) 1.5 DCM rt 2h 0 (1a~100%) 2 [Rh(cod)Cl] 2 (2) 1.5 DCM rt 2h 0 (1a ~100%) 3 Rh(norbornadiene) 2 BF 4 (2) 1.5 DCM rt 2h 0 (1a ~100%) 4 Rh(ethylene) 2 Cl (2) 1.5 DCM rt 2h 0 (1a ~100%) 5 Rh 2 (OOct) 4 (2) 1.5 DCM rt 2h 30 (+ 70% 1a) 6 Rh 2 (OPiv) 4 (2) 1.5 DCM rt 2h 35 (+ 55% 1a) 7 Rh 2 (TFA) 4 (2) 1.5 DCM rt 2h 20 (+ 80% 1a) 8 Rh 2 (TPA) 4 (2) 1.5 DCM rt 2h 30 (+ 70% 1a) 9 Rh 2 (OAc) 4 (2) 1.5 DCM rt 2h 30 (+ 70% 1a) 10 Rh(OOct) 4 (2) 2.0 DCM rt 5h 50 (+ 30% 1a) 11 Rh 2 (OPiv) 4 (2) 2.0 DCM rt 5h 33 (+ 60% 1a) 12 Rh 2 (OAc) 4 (2) 2.0 DCM rt 5h 50 (+ 30% 1a) 13 Rh 2 (OAc) 4 (2) 2.0 1,2-DCE 60 o C 2h 50 (+ 30% 1a) 14 Rh 2 (OAc) 4 (2) 2.0 PhCl 100 o C 2h 40 (+ 50% 1a) 15 Rh 2 (OAc) 4 (2) 2.5 DCM rt 9h 60 (0% 1a) 16 Rh 2 (OAc) 4 (2) 2.5 CHCl 3 rt 17h 55 (0% 1a) 17 Rh 2 (OAc) 4 (2) 2.5 Et 2 O rt 19h 5 (+ 55% 1a) 18 Rh 2 (OAc) 4 (2) 2.5 THF rt 14h 0 (+ 40% 1a) 19 Rh 2 (OAc) 4 (2) 2.5 Tol rt 13h 50 (0% 1a) 20 Rh 2 (OAc) 4 (2) 2.5 C 6 H 5 CF 3 rt 18h 10 (+ 65% 1a) 21 Rh 2 (OAc) 4 (2) 4.0 DCM rt 6h 14 (0% 1a) 22 Rh 2 (OAc) 4 (1) 2.5 DCM rt 3h 40 (0% 1a) 23 Rh 2 (OAc) 4 (2) 2.5 DCM rt 3h 60 (0% 1a) 24 Rh 2 (OOct) 4 (2) 2.5 DCM rt 3h 30 (0% 1a) 25 Rh 2 (OAc) 4 (5) 2.5 DCM rt 3h 55 (0% 1a) a Yields are estimated based on 1 H NMR analysis of crude reaction mixture using 1,3,5- trimethoxy benzene as an internal reference. S11

12 3.2 Brief Screening for Asymmetric Version Entry [Rh] (2 mol%) time yield(%) a er b 1-18h 0 (1a ~ 100%) - 2 Rh (R-DOSP) h 70 50:50 3 Rh 2 (R-PTAD) 4 15h 75 50:50 4 Rh 2 (S-PTTL) 4 3h 80 50:50 5 Rh 2 (S-TBPTTL) 4 2h :50 6 Rh 2 (2Cl-TPCP) 4 15h 72 50:50 a Yields are estimated based on 1 H NMR analysis of crude reaction mixture using 1,3,5-trimethoxy benzene as an internal reference b Determined by HPLC using a chiral stationary phase (conditions: column ADH, 90:10 Hex:iPrOH, 254 nm, 1 ml.min -1, 1 = 10.7min, 2 = 12.2 min) Structures of Rhodium catalysts: S12

13 General Procedure B: An oven-dried round bottom flask is charged with isoxazol-5- one 1 (1 equiv) and Rh 2 (OAc) 4 (2 mol %). The flask is evacuated and backfilled with argon three times. Then, DCM (0.1 M) is added. The donor-acceptor diazocompound 2 (2.5 equiv.) is dissolved in DCM (0.1 M) and added over 1h using a syringe pump to the previously prepared solution, under argon, at room temperature. After the slow addition has ceased, the reaction mixture is allowed to stir at room temperature for an additional 1h. Finally, the reaction mixture is concentrated under reduced pressure and purified by flash column chromatography to afford the target compound 3. General Procedure C: Under Ar, a round bottom flask is charged with the diazocompound 2 (0.15 mmol, 1.5 equiv.), p-tsoh.h 2 O (0.15 mmol, 1.5 equiv), and CHCl 3 (1 ml). The reaction is allowed to stir at rt until full consumption of diazocompound 2, as indicated by TLC analysis. Then, the isoxazol-5-one (0.1 mmol, 1 equiv.) in CHCl 3 (0.5 ml) is added at rt, followed by Et 3 N (0.15 mmol, 1.5 equiv.). The reaction mixture is heated at 60 o C overnight. Finally, the reaction is quenched with a saturated aqueous solution of NaHCO 3, extracted with DCM (3x), dried and concentrated. Purification by flash column chromatography affords the title compounds in the stated yields. General Procedure D: If desired, 2-aryl-2-tosyloxy ester intermediates 6 can be isolated. In this case, one should start as indicated in general procedure C, using DCM as solvent (0.2M). Upon full consumption of starting diazocompound 2, the reaction is quenched with a S13

14 saturated aqueous solution of NaHCO 3, extracted with DCM (3x), dried and concentrated. Purification by flash column chromatography affords the corresponding tosylates 6 in high yields. ethyl 2-(4-bromophenyl)-4-butyl-6-oxo-3,6-dihydro-2H-1,3-oxazine-2-carboxylate (3a) Prepared as described by the general procedure B using isoxazol-5-one 1a (28 mg, 0.2 mmol) and diazocompound 2a (134 mg, 0.5 mmol). Purification by flash column chromatography (SiO 2, gradient Hex - 9:1 Hex:AcOEt - 8:2 Hex:AcOEt) affords the title compound as pale yellow solid (46 mg, 60%). 1 H (CDCl 3, 500 MHz) : (m, 4H), 5.99 (s, 1H), 4.88 (s, 1H), (m, 2H), (m, 2H), 1.57 (quint., J = 7.5 Hz, 2H), (m, 2H), 1.24 (t, J = 7.0 Hz, 3H), 0.93 (t, J = 7.0 Hz, 3H). 13 C (CDCl 3, 125 MHz) : 168.5, 162.4, 161.0, 135.2, 131.9, 127.4, 124.3, 90.7, 87.6, 63.5, 33.3, 28.8, 22.1, 13.9, IR (ATR, cm -1 ): 3246 (br w), 2985 (w), 2957 (w), 2930 (w), 2871 (w), 1744 (s), 1674 (s), 1585 (s), 1514 (s), 1488 (s), 1467 (m), 1453 (m), 1398 (m), 1290 (m), 1258 (s), 1229 (s). HRMS (NSI+): Calcd. for [C 17 H 20 BrNO 4 +H] + : Found: X-ray 3a (CCDC ) Bond precision: C-C = A Wavelength= Cell: a=6.3863(3) b= (6) c= (3) alpha= (3) beta= (4) gamma= (4) Temperature: 173 K Calculated Reported Volume (7) (7) Space group P -1 P -1 Hall group -P 1 -P 1 Moiety formula C17 H20 Br N O4 C17 H20 Br N O4 Sum formula C17 H20 Br N O4 C17 H20 Br N O4 S14

15 Mr Dx,g cm Z 2 2 Mu (mm-1) F F000' h,k,lmax 7,14,14 7,14,14 Nref Tmin,Tmax 0.289, ,1.000 Tmin' Correction method= # Reported T Limits: Tmin=0.390 Tmax=1.000 AbsCorr = MULTI-SCAN Data completeness= Theta(max)= R(reflections)= ( 3106) wr2(reflections)= ( 3230) S = Npar= 214 ethyl (3b) 2-(4-bromophenyl)-4-isopropyl-6-oxo-3,6-dihydro-2H-1,3-oxazine-2-carboxylate Prepared as described by the general procedure B using isoxazol-5-one 1b (25 mg, 0.2 mmol) and diazocompound 2a (134 mg, 0.5 mmol). Purification by flash column chromatography (SiO 2, gradient Hex - 9:1 Hex:AcOEt - 8:2 Hex:AcOEt - 7:3 Hex-AcOEt) affords the title compound as a white solid (40 mg, 55%). 1 H (CDCl 3, 400 MHz) : (m, 4H), 5.86 (s, 1H), 4.90 (s, 1H), (m, 2H), 2.48 (sept., J = 7.0 Hz, 1H), 1.23 (t, J = 6.8 Hz, 3H), 1.18 (d, J = 7.0 Hz, 6H). 13 C (CDCl 3, 100 MHz) : 168.5, 165.7, 162.7, 135.2, 131.9, 127.4, 124.3, 89.0, 87.4, 63.5, 32.4, 20.2, IR (ATR, cm -1 ): 3258 (br w), 2966 (w), 2931 (w), 1744 (s), 1671 (s), 1578 (s), 1511 (s), 1488 (s), 1462 (m), 1449 (m), 1397 (w), 1313 (w), 1289 (w), 1257 (w), 1223 (s), 1180 (w). HRMS (NSI+): Calcd. for [C 16 H 18 BrNO 4 +H ] + : Found: This molecule has been also prepared in a preparative scale, following General Procedure B: isoxazol-5-one 1b (127 mg, 1 mmol) and Rh 2 (OAc) 4 (8.8 mg, 2 mol %) are dissolved in DCM (5 ml). Slow addition of diazocompound 2a (670 mg, 2.5 mmol) in DCM (5 ml) over 5h (which corresponds to the same rate of 1 ml.h -1 established in the general procedure B), followed by additional stirring at rt for 2h produces the same S15

16 target compound. After concentration, the title compound can be purified by flash column chromatography as previously described to afford a white solid (235 mg, 64%). The use of general procedure C employing isoxazol-5-one 1b (13 mg, 0.1 mmol) and diazocompound 2a (40 mg, 0.15 mmol) affords the title compound as a white solid (17 mg, 46%) ethyl 2-(4-bromophenyl)-4-methyl-6-oxo-3,6-dihydro-2H-1,3-oxazine-2-carboxylate (3c) Prepared as described by the general procedure B using isoxazol-5-one 1c (20 mg, 0.2 mmol) and diazocompound 2a (134 mg, 0.5 mmol). Purification by flash column chromatography (SiO 2, gradient Hex - 9:1 Hex:AcOEt - 8:2 Hex:AcOEt - 7:3 Hex:AcOEt) affords the title compound as a white solid (34 mg, 50%). 1 H (CDCl 3, 500 MHz) : 7.51 (app s, 4H), 6.25 (s, 1H), 4.84 (s, 1H), (m, 2H), 2.05 (s, 3H), 1.23 (t, J = 7.5 Hz, 3H). 13 C (CDCl 3, 125 MHz) : 168.5, 162.3, 157.5, 135.1, 131.9, 127.4, 124.3, 91.3, 87.8, 63.5, 19.7, IR (ATR, cm -1 ): 3249 (br w), 2994 (w), 1738 (s), 1675 (s), 1601 (m), 1586 (s), 1519 (s), 1489 (s), 1397 (m), 1389 (m), 1290 (w), 1258 (w), 1227 (s). HRMS (NSI+): Calcd. for [C 14 H 14 BrNO 4 +H] + : Found: The use of general procedure C employing isoxazol-5-one 1c (10 mg, 0.1 mmol) and diazocompound 2a (40 mg, 0.15 mmol) affords the title compound as a white solid (17 mg, 50%) ethyl 2-(4-bromophenyl)-5-ethyl-4-methyl-6-oxo-3,6-dihydro-2H-1,3-oxazine-2- carboxylate (3d) Prepared as described by the general procedure B using isoxazol-5-one 1d (25 mg, 0.2 mmol) and diazocompound 2a (134 mg, 0.5 mmol). Purification by flash column chromatography (SiO 2, gradient Hex - 9:1 Hex:AcOEt - 8:2 Hex:AcOEt - 7:3 Hex:AcOEt) affords the title compound as a S16

17 yellow solid (37 mg, 51%). 1 H (CDCl 3, 500 MHz) : 7.51 (app s, 4H), 5.62 (s, 1H), (m, 2H), (m, 2H), 2.04 (s, 3H), 1.23 (t, J = 7.0 Hz, 3H), 0.90 (t, J = 7.5 Hz, 3H). 13 C (CDCl 3, 125 MHz) : 169.2, 162.8, 151.8, 135.2, 131.8, 127.4, 124.2, 105.5, 87.2, 63.3, 18.9, 17.3, 14.0, IR (ATR, cm -1 ): 3308 (br w), 2979 (w), 2937 (w), 2907 (w), 1740 (s), 1686 (s), 1604 (m), 1588 (m), 1509 (w), 1488 (s), 1462 (w), 1397 (m), 1369 (w), 1235 (s), 1200 (s). HRMS (NSI+): Calcd. for [C 16 H 18 BrNO 4 +H] + : Found: The use of general procedure C employing isoxazol-5-one 1d (13 mg, 0.1 mmol) and diazocompound 2a (40 mg, 0.15 mmol) affords the title compound as a brown/orange solid solid (11 mg, 29%) ethyl 2-(4-bromophenyl)-4-oxo-1,4,5,6,7,8-hexahydro-2H-benzo[d][1,3]oxazine-2- carboxylate (3e) Prepared as described by the general procedure B using isoxazol-5-one 1e (28 mg, 0.2 mmol) and diazocompound 2a (134 mg, 0.5 mmol). Purification by flash column chromatography (SiO 2, gradient Hex - 9:1 Hex:AcOEt - 8:2 Hex:AcOEt - 7:3 Hex:AcOEt) affords the title compound as a white solid (61 mg, 80%). 1 H (CDCl 3, 500 MHz) : 7.52 (app s, 4H), 5.45 (s, 1H), (m, 2H), (m, 3H), (m, 5H), 1.23 (t, J = 6.0 Hz, 3H). 13 C (CDCl 3, 125 MHz) : 168.9, 162.8, 153.4, 135.6, 131.9, 127.5, 124.2, 101.1, 87.4, 63.3, 27.9, 22.1, 21.7, 21.4, IR (ATR, cm -1 ): 3282 (m), 2987 (w), 2956 (w), 2918 (w), 1732 (s), 1674 (s), 1599 (s), 1525 (s), 1488 (s), 1417 (m), 1397 (m), 1304 (m), 1258 (s), 1225 (s), 1171 (w), 1150 (m), 1117 (w), 1070 (w), 1035 (m), 1025 (s), 1005 (s). HRMS (NSI+): Calcd. for [C 17 H 18 BrNO 4 +H] + : Found: The use of general procedure C employing isoxazol-5-one 1e (14 mg, 0.1 mmol) and diazocompound 2a (40 mg, 0.15 mmol) affords the title compound as a white solid (13 mg, 34%) S17

18 ethyl 2-(4-bromophenyl)-4-oxo-1,2,4,5,6,7,8,9-octahydrocyclohepta[d][1,3]oxazine-2- carboxylate (3f) Prepared as described by the general procedure B using isoxazol-5-one 1f (30 mg, 0.2 mmol) and diazocompound 2a (134 mg, 0.5 mmol). Purification by flash column chromatography (SiO 2, gradient Hex - 9:1 Hex:AcOEt - 8:2 Hex:AcOEt - 7:3 Hex:AcOEt) affords the title compound as a pale orange foam (61 mg, 79%). 1 H (CDCl 3, 500 MHz) : (m, 4H), 5.92 (s, 1H), (m, 2H), (m, 3H), (m, 1H), (m, 4H), (m, 2H), 1.22 (t, J = 7.0 Hz, 3H). 13 C (CDCl 3, 125 MHz) : 169.0, 163.4, 159.6, 135.2, 131.8, 127.4, 124.1, 104.1, 86.9, 63.3, 34.4, 31.7, 27.1, 25.1, 24.9, IR (ATR, cm -1 ): 3280 (br w), 2925 (w), 2850 (w), 1741 (s), 1672 (s), 1587 (s), 1517 (s), 1488 (s), 1445 (w), 1398 (w), 1358 (w), 1227 (s), 1178 (s), 1152 (s), 1096 (s). HRMS (NSI+): Calcd. for [C 18 H 20 BrNO 4 +H] + : Found: ethyl 4-isopropyl-6-oxo-2-phenyl-3,6-dihydro-2H-1,3-oxazine-2-carboxylate (3g) Prepared as described by the general procedure B using isoxazol-5-one 1b (25 mg, 0.2 mmol) and diazocompound 2b (95 mg, 0.5 mmol). Purification by flash column chromatography (SiO 2, gradient Hex - 9:1 Hex:AcOEt - 8:2 Hex:AcOEt - 7:3 Hex:AcOEt) affords the title compound as a pale yellow oil (29 mg, 51%). 1 H (CDCl 3, 500 MHz) : (m, 2H), (m, 3H), 5.90 (s, 1H), 4.90 (s, 1H), (m, 2H), (sept, J = 7.0 Hz, 1H), 1.23 (t, J = 7.5 Hz, 3H), 1.20 (d, J = 7.0 Hz, 6H) 13 C (CDCl 3, 125 MHz) : 169.2, 166.2, 163.2, 135.9, 129.9, 128.7, 125.6, 88.6, 88.0, 63.2, 32.3, 20.3, 20.2, IR (ATR, cm -1 ): 3256 (br w), 2972 (w), 1745 (s), 1679 (s), 1584 (s), 1495 (s)1451 (m), 1388 (w), 1367 (w), 1296 (w), 1232 (s), 1194 (m), 1145 (w), 1096 (w). HRMS (NSI+): Calcd. for [C 16 H 19 NO 4 +H] + : Found: S18

19 The use of general procedure C employing isoxazol-5-one 1b (13 mg, 0.1 mmol) and diazocompound 2b (29 mg, 0.15 mmol) affords the title compound as a transparent oil (9 mg, 31%) isopropyl 4-isopropyl-6-oxo-2-phenyl-3,6-dihydro-2H-1,3-oxazine-2-carboxylate (3h) Prepared as described by the general procedure B using isoxazol-5-one 1b (25 mg, 0.2 mmol) and diazocompound 2c (102 mg, 0.5 mmol). Purification by flash column chromatography (SiO 2, gradient Hex - 9:1 Hex:AcOEt - 8:2 Hex:AcOEt - 7:3 Hex:AcOEt) affords the title compound as a white solid (38 mg, 64%). 1 H (CDCl 3, 500 MHz) : (m, 2H), (m, 3H), 5.91 (s, 1H), 5.05 (sept., J = 7.0 Hz, 1H), 4.90 (s, 1H), 2.50 (sept., J = 7.0 Hz, 1H), 1.27 (d, J = 6.5 Hz, 3H), 1.20 (d, J = 7.0 Hz, 6H), 1.14 (d, J = 6.5 Hz, 3H). 13 C (CDCl 3, 125 MHz) : 168.6, 166.2, 163.3, 135.9, 129.8, 128.6, 125.6, 88.5, 88.0, 71.4, 32.3, 21.6, 21.2, 20.3 (x2). IR (ATR, cm -1 ): 3257 (br w), 2979 (w), 2935 (w), 1741 (s), 1682 (s), 1584 (s), 1495 (s), 1466 (m), 1451 (m), 1375 (w), 1238 (s), 1193 (w), 1096 (s). HRMS (NSI+): Calcd. for [C 17 H 21 NO 4 +H] + : Found: tert-butyl 4-isopropyl-6-oxo-2-phenyl-3,6-dihydro-2H-1,3-oxazine-2-carboxylate (3i) Prepared as described by the general procedure B using isoxazol-5-one 1b (25 mg, 0.2 mmol) and diazocompound 2d (109 mg, 0.5 mmol). Purification by flash column chromatography (SiO 2, gradient Hex - 9:1 Hex:AcOEt - 8:2 Hex:AcOEt - 7:3 Hex:AcOEt) affords the title compound as a white solid (32 mg, 51%). 1 H (CDCl 3, 500 MHz) : (m, 2H), (m, 3H), 5.90 (s, 1H), 4.89 (s, 1H), 2.49 (sept., J = 7.0 Hz, 1H), 1.41 (s, 9H), 1.19 (d, J = 7.0 Hz, 6H). 13 C (CDCl 3, 125 MHz) : 167.8, 166.0, 163.6, 136.3, 129.6, 128.5, 125.6, 88.6, 88.0, 84.5, 32.3, 27.6, 20.3 (x2). IR (ATR, cm -1 ): 3246 (br w), 2964 (w), 2929 (w), 1738 (s), 1677 (s), 1582 (m), 1497 (s), 1452 (m), 1369 (m), 1253 (s), 1149 (s), 1076 (m). HRMS (NSI+): Calcd. for [C 18 H 23 NO 4 +H] + : Found: S19

20 2-(triisopropylsilyl)ethyl carboxylate (3j) Prepared as described by the general procedure B using isoxazol-5-one 1b (25 mg, 0.2 mmol) and diazocompound 2e (174 mg, 0.5 mmol). Purification by flash column chromatography (SiO 2, gradient Hex - 9:1 Hex:AcOEt - 8:2 Hex:AcOEt - 7:3 Hex:AcOEt) affords the title compound as a pale yellow solid (44 mg, 50%). 1 H (CDCl 3, 500 MHz) : (m, 2H), (m, 3H), 5.95 (s, 1H), 4.90 (s, 1H), (m, 2H), 2.50 (sept., J = 7.0 Hz, 1H), 1.20 (d, J = 7.0 Hz, 6H), (m, 2H), 1.00 (s, 21H). 13 C (CDCl 3, 125 MHz) : 169.1, 165.9, 163.2, 136.0, 129.8, 128.6, 125.7, 88.6, 87.9, 66.1, 32.3, 20.3, 20.2, 18.6, 10.8, IR (ATR, cm -1 ): 3258 (br w), 2942 (w), 2866 (w), 1741 (s), 1683 (s), 1585 (m), 1496 (s), 1464 (m), 1386 (w), 1231 (s), 1191 (m), 1145 (w). HRMS (NSI+): Calcd for [C 25 H 39 NO 4 Si+H] + : Found: isopropyl-6-oxo-2-phenyl-3,6-dihydro-2H-1,3-oxazine-2- methyl 2-([1,1'-biphenyl]-4-yl)-4-isopropyl-6-oxo-3,6-dihydro-2H-1,3-oxazine-2- carboxylate (3k) Prepared as described by the general procedure B using isoxazol-5-one 1b (25 mg, 0.2 mmol) and diazocompound 2f (126 mg, 0.5 mmol). Purification by flash column chromatography (SiO 2, gradient Hex - 9:1 Hex:AcOEt - 8:2 Hex:AcOEt - 7:3 Hex:AcOEt) affords the title compound as a white foam (41 mg, 59%). 1 H (CDCl 3, 500 MHz) : 7.70 (d, J = 8.7 Hz, 2H), 7.61 (d, J = 8.7 Hz, 2H), 7.55 (d, J = 7.5 Hz, 2H), 7.44 (t, J = 7.5 Hz, 2H), 7.37 (t, J = 7.5 Hz, 1H), 6.08 (s, 1H), 4.92 (s, 1H), 3.80 (s, 3H), 2.53 (sept, J = 7.0 Hz, 1H), 1.21 (d, J = 7.0 Hz, 3H), 1.20 (d, J = 7.0 Hz, 3H). 13 C (CDCl 3, 125 MHz) : 169.8, 166.5, 163.1, 142.9, 140.0, 134.6, 128.9, 127.8, 127.4, 127.1, 126.1, 88.5, 88.1, 53.8, 32.4, 20.3, IR (ATR, cm -1 ): 3255 (br w), 2969 (w), 1748 (s), 1682 (s), 1586 (s), 1502 (s), 1486 (s), 1407 (w), 1312 (w), 1235 (s), 1193 (w), 1145 (w), 1099 (w). HRMS (NSI+): Calcd. for [C 21 H 21 NO 4 +H] + : Found: S20

21 The use of general procedure C employing isoxazol-5-one 1b (13 mg, 0.1 mmol) and diazocompound 2g (52 mg, 0.15 mmol) affords the title compound as a orange foam (10 mg, 22%) 2,2,2-trichloroethyl 2-(4-(tert-butyl)phenyl)-4-isopropyl-6-oxo-3,6-dihydro-2H-1,3- oxazine-2-carboxylate (3l) Prepared as described by the general procedure B using isoxazol-5-one 1b (25 mg, 0.2 mmol) and diazocompound 2g (174 mg, 0.5 mmol). Purification by flash column chromatography (SiO 2, gradient Hex - 9:1 Hex:AcOEt - 8:2 Hex:AcOEt) affords the title compound as a pale orange foam (47 mg, 53%). 1 H (CDCl 3, 500 MHz) : 7.62 (d, J = 8.7 Hz, 2H), 7.43 (d, J = 8.7 Hz, 2H), 5.77 (br s, 1H), 4.99 (s, 1H), 4.79 (s, 2H), 2.53 (sept., J = 7.0 Hz, 1H), 1.31 (s, 9H), 1.21 (d, J = 7.0 Hz, 6H). 13 C (CDCl 3, 125 MHz) : 168.5, 166.4, 162.8, 153.6, 131.6, 125.9, 125.2, 93.9, 89.2, 88.3, 75.1, 34.7, 32.3, 31.2, 20.3, IR (ATR, cm -1 ): 3187 (w), 2966 (w), 2160 (w), 2030 (w), 1768 (s), 1680 (s), 1605 (s), 1501 (s), 1386 (w), 1363 (w), 1316 (w), 1264 (s), 1197 (s), 1145 (s). HRMS (NSI+): Calcd. for [C 20 H 24 Cl 3 NO 4 +H] + : Found: methyl 2-(3,4-dichlorophenyl)-4-isopropyl-6-oxo-3,6-dihydro-2H-1,3-oxazine-2- carboxylate (3m) Prepared as described by the general procedure B using isoxazol-5-one 1b (25 mg, 0.2 mmol) and diazocompound 2h (123 mg, 0.5 mmol). Purification by flash column chromatography (SiO 2, gradient Hex - 9:1 Hex:AcOEt - 8:2 Hex:AcOEt - 7:3 Hex:AcOEt) affords the title compound as a white solid (40 mg, 59%). 1 H (CDCl 3, 500 MHz) : 7.72 (d, J = 2.0 Hz, 1H), (m, 2H), 6.05 (s, 1H), 4.91 (s, 1H), 3.81 (s, 3H), 2.52 (sept., J = 7.0 Hz, 1H), 1.20 (d, J = 7.0 Hz, 6H). 13 C (CDCl 3, 125 MHz) : 168.7, 166.0, 162.3, 136.2, 134.5, 133.2, 130.8, 127.9, 125.2, 89.0, 86.9, 54.1, 32.4, 20.2 (x2). IR (ATR, cm -1 ): 3283 (br w), 2971 (w), 1747 (s), 1677 (s), 1578 (s), 1510 (s), 1472 (m), 1431 (w), 1385 (w), 1331 (w), 1290 (w), 1234 (s), 1137 (w), 1098 (w). S21

22 HRMS (NSI+): Calcd. for [C 15 H 15 Cl 2 NO 4 +H] + : Found: tert-butyl 4-isopropyl-2-(naphthalen-2-yl)-6-oxo-3,6-dihydro-2H-1,3-oxazine-2- carboxylate (3n) Prepared as described by the general procedure B using isoxazol-5-one 1b (25 mg, 0.2 mmol) and diazocompound 2i (134 mg, 0.5 mmol). Purification by flash column chromatography (SiO 2, gradient Hex - 9:1 Hex:AcOEt - 8:2 Hex:AcOEt - 7:3 Hex:AcOEt) affords the title compound as a white solid (36 mg, 50%). 1 H (CDCl 3, 500 MHz) : 8.10 (s, 1H), (m, 3H), 7.71 (dd, J = 2.0 Hz, J = 8.5 Hz, 1H), (m, 2H), 6.06 (d, J = 15.0 Hz, 1H), (m, 1H), 2.51 (sept., J = 7.0 Hz, 1H), 1.41 (s, 9H), 1.21 (d, J = 7.0 Hz, 3H), 1.20 (d, J = 7.0 Hz, 3H). 13 C (CDCl 3, 125 MHz) : 167.8, 166.0, 163.6, 133.7, (x2), 132.7, 128.5, 127.6, 127.0, 126.6, 125.6, 122.7, 88.7, 88.1, 84.7, 32.4, 27.6, 20.3 (x2). IR (ATR, cm -1 ): 3254 (br w), 2974 (w), 1737 (s), 1672 (s), 1579 (s), 1502 (s), 1395 (w), 1370 (m), 1311 (w), 1248 (s), 1148 (s), 1097 (s). HRMS (NSI+): Calcd. for [C 22 H 25 NO 4 +H] + : Found: The use of general procedure C employing isoxazol-5-one 1b (13 mg, 0.1 mmol) and diazocompound 2i (40 mg, 0.15 mmol) affords the title compound as a white solid (15 mg, 40%) (trimethylsilyl)methyl 2-(4-bromophenyl)-4-isopropyl-6-oxo-3,6-dihydro-2H-1,3-oxazine- 2-carboxylate (3o) Prepared as described by the general procedure B using isoxazol-5-one 1b (25 mg, 0.2 mmol) and diazocompound 2j (164 mg, 0.5 mmol). Purification by flash column chromatography (SiO 2, gradient Hex - 9:1 Hex:AcOEt - 8:2 Hex:AcOEt - 7:3 Hex:AcOEt) affords the title compound as an orange solid (45 mg, 54%). 1 H (CDCl 3, 500 MHz) : 7.50 (app s, 4H), 5.99 (s, 1H), 4.89 (s, 1H), 3.93 (s, 2H), 2.49 (sept, J = 6.5 Hz, 1H), 1.18 (d, J = 7.0 Hz, 6H), 0.05 (s, 9H). S22

23 13 C (CDCl 3, 125 MHz) : 169.2, 165.8, 162.8, 135.6, 131.6, 127.5, 124.2, 89.0, 87.6, 61.4, 32.4, 20.3, 20.2, IR (ATR, cm -1 ): 3243 (br w), 2971 (w), 2160 (w), 2030 (w), 1734 (s), 1673 (s), 1580 (s), 1516 (s), 1488 (m), 1397 (w), 1296 (m), 1249 (s), 1226 (s), 1092 (w), 1071 (w), 1051 (w). HRMS (NSI+): Calcd. for [C 18 H 24 BrNO 4 Si+H] + : Found: The use of general procedure C employing isoxazol-5-one 1b (13 mg, 0.1 mmol) and diazocompound 2j (49 mg, 0.15 mmol) affords the title compound as a white solid (24 mg, 55%) 2-(triisopropylsilyl)ethyl 2-(3,4-dimethoxyphenyl)-4-isopropyl-6-oxo-3,6-dihydro-2H-1,3- oxazine-2-carboxylate (3p) Prepared as described by the general procedure B using isoxazol-5-one 1b (25 mg, 0.2 mmol) and diazocompound 2k (203 mg, 0.5 mmol). Purification by flash column chromatography (SiO 2, gradient Hex - 9:1 Hex:AcOEt - 8:2 Hex:AcOEt - 7:3 Hex:AcOEt) affords the title compound as a white foam (71 mg, 71%). 1 H (CDCl 3, 500 MHz) : 7.17 (d, J = 2.0 Hz, 1H), 7.12 (dd, J = 2.0 Hz, J = 8.0 Hz, 1H), 6.8 (d, J = 8.0 Hz, 1H), 5.95 (s, 1H), 4.88 (s, 1H), (m, 2H), 3.87 (s, 3H), 3.86 (s, 3H), 2.49 (sept., J = 7.0 Hz, 1H), 1.18 (d, J = 7.0 Hz, 6H), (m, 2H), 0.99 (s, 21H). 13 C (CDCl 3, 125 MHz) : 169.3, 166.1, 163.4, 150.0, 149.0, 128.3, 118.1, 110.7, 108.9, 88.4, 87.8, 65.9, 56.0, 55.9, 32.3, 20.3 (x2), 18.6, 10.8, IR (ATR, cm -1 ): 3269 (w), 2941 (w), 2866 (w), 1740 (s), 1682 (s), 1587 (m), 1502 (s), 1464 (s), 1417 (w), 1266 (s), 1238 (s), 1170 (s), 1144 (m), 1025 (s). HRMS (NSI+): Calcd. for [C 27 H 43 NO 6 Si+H] + : Found: Preparation of 2-aryl-2-tosyloxy-esters ethyl 2-(4-bromophenyl)-2-(tosyloxy)acetate (6a) Prepared as described by the general procedure D using diazocompound 2a (134 mg, 0.5 mmol) and ptsoh.h 2 O (143 mg, 0.75 mmol) in DCM (2.5mL). Purification by flash column S23

24 chromatography (SiO 2, gradient Hex - 95:5 Hex:AcOEt - 9:1 Hex:AcOEt) affords the title compound as a transparent oil (188 mg, 91%). 1 H (CDCl 3, 600 MHz) : 7.74 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H), 5.72 (s, 1H), (m, 2H), 2.43 (s, 3H), 1.18 (t, J = 7.2 Hz, 3H). 13 C (CDCl 3, 100 MHz) : 166.9, 145.2, 133.1, 131.9, 131.8, 129.7, 129.0, 128.0, 123.9, 78.0, 62.3, 21.7, IR (ATR, cm -1 ): 2968 (w), 2929 (w), 1792 (s), 1731 (m), 1623 (w), 1432 (m), 1393 (m), 1374 (m), 1341 (w), 1201 (m), 1166 (s), 1034 (m), 1000 (m), 909 (w), 874 (s). HRMS (NSI+): Calcd. for [C 17 H 17 BrO 5 S+NH 4 ] + : Found: ethyl 2-phenyl-2-(tosyloxy)acetate (6b) Prepared as described by the general procedure D using diazocompound 2b (38 mg, 0.2 mmol) and ptsoh.h 2 O (57 mg, 0.3 mmol) in DCM (1 ml). Purification by flash column chromatography (SiO 2, gradient Hex- 95:5 Hex:AcOEt - 9:1 Hex:AcOEt) affords the title compound as a transparent oil (65 mg, 97%). 1 H (CDCl 3, 500 MHz) : 7.77 (d, J = 8.5 Hz, 2H), (m, 7H), 5.77 (s, 1H), (m, 2H), 2.42 (s, 3H), 1.18 (t, J = 7.0 Hz, 3H). 13 C (CDCl 3, 125 MHz) : 167.3, 145.0, 133.4, 132.8, 129.7, 129.6, 128.8, 128.0, 127.5, 78.9, 62.1, 21.7, IR (ATR, cm -1 ): 2983 (w), 2160 (w), 1756 (s), 1598 (w), 1497 (w), 1456 (w), 1368 (s), 1269 (m), 1210 (m), 1190 (s), 1174 (s), 1095 (m). HRMS (NSI+): Calcd. for [C 17 H 18 O 5 S+H] + : Found: ,2,2-trichloroethyl 2-(4-(tert-butyl)phenyl)-2-(tosyloxy)acetate (6c) Prepared as described by the general procedure D using diazocompound 2g (70 mg, 0.2 mmol) and ptsoh.h 2 O (57 mg, 0.3 mmol) in DCM (1 ml). Purification by flash column chromatography (SiO 2, gradient Hex- 95:5 Hex:AcOEt - 9:1 Hex:AcOEt) affords the title compound as a transparent oil (100 mg, 100%). S24

25 1 H (CDCl 3, 500 MHz) : 7.76 (d, J = 8.5 Hz, 2H), 7.33 (d, J = 8.7 Hz, 2H), 7.31 (d, J = 8.7 Hz, 2H), 7.26 (d, J = 8.5 Hz, 2H), 5.90 (s, 1H), 4.76 (d, J = 12.0 Hz, 1H), 4.66 (d, J = 12.0 Hz, 1H), 2.41 (s, 3H), 1.28 (s, 9H). 13 C (CDCl 3, 125 MHz) : 166.1, 153.2, 145.1, 133.2, 129.7, 128.9, 128.1, 127.4, 125.8, 94.1, 78.3, 74.4, 34.7, 31.2, IR (ATR, cm -1 ): 2962 (w), 2160 (w), (w), 1777 (s), 1598 (w), 1515 (w), 1448 (w), 1368 (s), 1269 (w), 1210 (w), 1190 (s), 1177 (s), 1157 (s), 1096 (w). HRMS (NSI+): Calcd. for [C 21 H 23 Cl 3 O 5 S+NH 4 ] + : Found: tert-butyl 2-(naphthalen-2-yl)-2-(tosyloxy)acetate (6d) Prepared as described by the general procedure D using diazocompound 2i (54 mg, 0.2 mmol) and ptsoh.h 2 O (57 mg, 0.3 mmol) in DCM (1 ml). Purification by flash column chromatography (SiO 2, gradient Hex- 95:5 Hex:AcOEt - 9:1 Hex:AcOEt) affords the title compound as a pale yellow solid (85 mg, 100%). 1 H (CDCl 3, 500 MHz) : (m, 6H), (m, 2H), 7.43 (dd, J = 1.5 Hz, J = 8.5 Hz, 1H), 7.22 (d, J = 8.0 Hz, 2H), 5.83 (s, 1H), 2.35 (s, 3H), 1.36 (s, 9H). 13 C (CDCl 3, 125 MHz) : 166.2, 144.9, 133.6, 133.5, 132.8, 130.5, 129.6, 128.6, 128.3, 128.0, 127.7, 127.5, 126.9, 126.5, 124.2, 83.4, 79.5, 27.7, IR (ATR, cm -1 ): 2977 (w), 2160 (w), 1978 (w), 1751 (s), 1596 (w), 1510 (w), 1458 (w), 1369 (s), 1332 (m), 1284 (w), 1259 (w), 1190 (s), 1180 (s), 1148 (s), 1094 (w). HRMS (NSI+): Calcd. for [C 23 H 24 O 5 S+NH 4 ] + : Found: (trimethylsilyl)methyl 2-(4-bromophenyl)-2-(tosyloxy)acetate (6e) Prepared as described by the general procedure D using diazocompound 2j (65 mg, 0.2 mmol) and ptsoh.h 2 O (57 mg, 0.3 mmol) in DCM (1 ml). Purification by flash column chromatography (SiO 2, gradient Hex- 95:5 Hex:AcOEt - 9:1 Hex:AcOEt) affords the title compound as a transparent oil (95 mg, 100%). 1 H (CDCl 3, 500 MHz) : 7.74 (d, J = 8.5 Hz, 2H), 7.42 (d, J = 8.5 Hz, 2H), 7.27 (d, J = 8.5 Hz, 2H), 7.20 (d, J = 8.5 Hz, 2H), 5.74 (s, 1H), 3.82 (d, J = 14.0 Hz, 1H), 3.78 (d, J = 14.0 Hz, 1H), 2.42 (s, 3H), (s, 9H). S25

26 13 C (CDCl 3, 125 MHz) : 167.5, 145.2, 133.2, 132.3, 131.9, 129.8, 128.9, 128.0, 123.8, 78.1, 59.9, 21.7, IR (ATR, cm -1 ): 2956 (w), 2160 (w), 1978 (w), 1755 (s), 1596 (w), 1489 (m), 1407 (m), 1372 (s), 1308 (m), 1250 (s), 1190 (s), 1175 (s), 1095 (w), 1071 (w). HRMS (NSI+): Calcd. for [C 19 H 23 BrO 5 SSi+NH 4 ] + : Found: S26

27 5. NMR Spectra 5.1 Isoxazol-5-ones Molecule 1a (400MHz, CDCl 3 ) S27

28 Molecule 1a (100MHz, CDCl 3 ) S28

29 Molecule 1b (500MHz, CDCl 3 ) S29

30 Molecule 1b (125MHz, CDCl 3 ) S30

31 Molecule 1c (500MHz, CDCl 3 ) S31

32 Molecule 1c (125MHz, CDCl 3 ) S32

33 Molecule 1d (500MHz, CDCl 3 ) S33

34 Molecule 1d (125MHz, CDCl 3 ) S34

35 Molecule 1e (500MHz, CDCl 3 ) S35

36 Molecule 1e (125MHz, CDCl 3 ) S36

37 Molecule 1f (500MHz, CDCl 3 ) S37

38 Molecule 1f (125MHz, CDCl 3 ) S38

39 5.2 Diazocompounds Molecule 2a (500MHz, CDCl 3 ) S39

40 Molecule 2a (125MHz, CDCl 3 ) S40

41 Molecule 2b (500MHz, CDCl 3 ) S41

42 Molecule 2b (125MHz, CDCl 3 ) S42

43 Molecule 2c (500MHz, CDCl 3 ) S43

44 Molecule 2c (125MHz, CDCl 3 ) S44

45 Molecule 2d (500MHz, CDCl 3 ) S45

46 Molecule 2d (125MHz, CDCl 3 ) S46

47 Molecule 2e (500MHz, CDCl 3 ) S47

48 Molecule 2e (125MHz, CDCl 3 ) S48

49 Molecule 2f (500MHz, CDCl 3 ) S49

50 Molecule 2f (125MHz, CDCl 3 ) S50

51 Molecule 2g (500MHz, CDCl 3 ) S51

52 Molecule 2g (125MHz, CDCl 3 ) S52

53 Molecule 2h (500MHz, CDCl 3 ) S53

54 Molecule 2h (125MHz, CDCl 3 ) S54

55 Molecule 2i (500MHz, CDCl 3 ) S55

56 Molecule 2i (125MHz, CDCl 3 ) S56

57 Molecule 2j (500MHz, CDCl 3 ) S57

58 Molecule 2j (125MHz, CDCl 3 ) S58

59 Molecule 2k (500MHz, CDCl 3 ) S59

60 Molecule 2k (125MHz, CDCl 3 ) S60

61 5.3 2,3-dihydro-6H-1,3-oxazin-6-ones Molecule 3a (500MHz, CDCl 3 ) S61

62 Molecule 3a (125MHz, CDCl 3 ) S62

63 Molecule 3b (600MHz, CDCl 3 ) S63

64 Molecule 3b (100MHz, CDCl 3 ) S64

65 Molecule 3c (500MHz, CDCl 3 ) S65

66 Molecule 3c (125MHz, CDCl 3 ) S66

67 Molecule 3d (500MHz, CDCl 3 ) S67

68 Molecule 3d (125MHz, CDCl 3 ) S68

69 Molecule 3e (500MHz, CDCl 3 ) S69

70 Molecule 3e (125MHz, CDCl 3 ) S70

71 Molecule 3f (500MHz, CDCl 3 ) S71

72 Molecule 3f (125MHz, CDCl 3 ) S72

73 Molecule 3g (500MHz, CDCl 3 ) S73

74 Molecule 3g (125MHz, CDCl 3 ) S74

75 Molecule 3h (500MHz, CDCl 3 ) S75

76 Molecule 3h (125MHz, CDCl 3 ) S76

77 Molecule 3i (500MHz, CDCl 3 ) S77

78 Molecule 3i (125MHz, CDCl 3 ) S78

79 Molecule 3j (500MHz, CDCl 3 ) S79

80 Molecule 3j (125MHz, CDCl 3 ) S80

81 Molecule 3k (500MHz, CDCl 3 ) S81

82 Molecule 3k (125MHz, CDCl 3 ) S82

83 Molecule 3l (500MHz, CDCl 3 ) S83

84 Molecule 3l (125MHz, CDCl 3 ) S84

85 Molecule 3m (500MHz, CDCl 3 ) S85

86 Molecule 3m (125MHz, CDCl 3 ) S86

87 Molecule 3n (500MHz, CDCl 3 ) S87

88 Molecule 3n (125MHz, CDCl 3 ) S88

89 Molecule 3o (500MHz, CDCl 3 ) S89

90 Molecule 3o (125MHz, CDCl 3 ) S90

91 Molecule 3p (500MHz, CDCl 3 ) S91

92 Molecule 3p (125MHz, CDCl 3 ) S92

93 5.4 2-aryl-2-tosyloxy esters Molecule 6a (600MHz, CDCl 3 ) S93

94 Molecule 6a (100MHz, CDCl 3 ) S94

95 Molecule 6b (500MHz, CDCl 3 ) S95

96 Molecule 6b (125MHz, CDCl 3 ) S96

97 Molecule 6c (500MHz, CDCl 3 ) S97

98 Molecule 6c (125MHz, CDCl 3 ) S98

99 Molecule 6d (500MHz, CDCl 3 ) S99

100 Molecule 6d (125MHz, CDCl 3 ) S100

101 Molecule 6e (500MHz, CDCl 3 ) S101

102 Molecule 6e (125MHz, CDCl 3 ) S102