Synlett, Table of Contents Synlett 2023; 34(18): 2169-2174DOI: 10.1055/a-2108-9895 cluster Modern Boron Chemistry: 60 Years of the Matteson Reaction N-Functionalization of 1,2-Azaborines Hyelee Lee a Department of Chemistry, Boston College, Chestnut Hill, MA 02467-3860, USA b Accent Therapeutics, Inc., 1050 Waltham Street, Suite 201, Lexington, MA 02421, USA , Marisol Alvarado a Department of Chemistry, Boston College, Chestnut Hill, MA 02467-3860, USA , Sarah Ingram a Department of Chemistry, Boston College, Chestnut Hill, MA 02467-3860, USA c Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA , Bo Li a Department of Chemistry, Boston College, Chestnut Hill, MA 02467-3860, USA , Shih-Yuan Liu ∗ a Department of Chemistry, Boston College, Chestnut Hill, MA 02467-3860, USA › Author Affiliations Recommend Article Abstract Buy Article All articles of this category Abstract General protocols for the N-functionalization of 1,2-azaborines with C(sp3), C(sp2), or C(sp) electrophiles are described. The syntheses of a new parental BN isostere of trans-stilbene and a BN isostere of a lisdexamfetamine derivative were accomplished with the developed methodology. Key words Key wordsazaborines - cross-coupling - BN heterocycles - N-functionalization - amination Full Text References References and Notes 1a Liu Z, Marder TB. Angew. Chem. Int. Ed. 2008; 47: 242 1b Bosdet MJ. D, Piers WE. Can. J. Chem. 2009; 87: 8 1c Campbell PG, Marwitz AJ. V, Liu S.-Y. Angew. Chem. Int. Ed. 2012; 51: 6074 1d Giustra ZX, Liu S.-Y. J. Am. Chem. Soc. 2018; 140: 1184 2 McConnell CR, Liu S.-Y. Chem. Soc. Rev. 2019; 48: 3436 3a Marwitz AJ. V, Abbey ER, Jenkins JT, Zakharov LN, Liu S.-Y. Org. Lett. 2007; 9: 4905 3b Lamm AN, Garner EB, Dixon DA, Liu S.-Y. Angew. Chem. Int. Ed. 2011; 50: 8157 3c Rudebusch GE, Zakharov LN, Liu S.-Y. Angew. Chem. Int. Ed. 2013; 52: 9316 3d Brown AN, Zakharov LN, Mikulas T, Dixon DA, Liu S.-Y. Org. Lett. 2014; 16: 3340 4 Pan J, Kampf JW, Ashe AJ. III. Org. Lett. 2007; 9: 679 5a Brown AN, Li B, Liu S.-Y. J. Am. Chem. Soc. 2015; 137: 8932 5b Brown AN, Li B, Liu S.-Y. Tetrahedron 2019; 75: 580 6a Baggett AW, Vasiliu M, Li B, Dixon DA, Liu S.-Y. J. Am. Chem. Soc. 2015; 137: 5536 6b Baggett AW, Guo F, Liu S.-Y, Jäkle F. Angew. Chem. Int. Ed. 2015; 54: 11191 7 McConnell CR, Haeffner F, Baggett AW, Liu S.-Y. J. Am. Chem. Soc. 2019; 141: 9072 8a Pan J, Kampf JW, Ashe AJ. III. Organometallics 2004; 23: 5626 8b Pan J, Kampf JW, Ashe AJ. III. Organometallics 2008; 27: 1345 8c Abbey ER, Lamm AN, Baggett AW, Zakharov LN, Liu S.-Y. J. Am. Chem. Soc. 2013; 135: 12908 8d Baggett AW, Liu S.-Y. J. Am. Chem. Soc. 2017; 139: 15259 For a study to access N-functionalized 2,1-borazaronaphthalenes, see: 9a Wang X, Davies GH. M, Koschitzky A, Wisniewski SR, Kelly CB, Molander GA. Org. Lett. 2019; 21: 2880 For a study to utilize 1,2-azaborinin-1-yls as anionic nitrogen ligands for main group elements, see: 9b Lindl F, Lamprecht A, Arrowsmith M, Khitro E, Rempel A, Dietz M, Wellnitz T, Bélanger-Chabot G, Stoy A, Paprocki V, Prieschl D, Lenczyk C, Ramler J, Lichtenberg C, Braunschweig H. Chem. Eur. J. 2023; 29: e202203345 For select examples, see: 10a Paul F, Patt J, Hartwig JF. J. Am. Chem. Soc. 1994; 116: 5969 10b Guram AS, Buchwald SL. J. Am. Chem. Soc. 1994; 116: 7901 10c Guram AS, Rennels RA, Buchwald SL. Angew. Chem. Int. Ed. 1995; 34: 1348 10d Louie J, Hartwig JF. Tetrahedron Lett. 1995; 36: 3609 For selected reviews, see: 10e Muci AR, Buchwald SL. Top. Curr. Chem. 2002; 219: 131 10f Hartwig JF. Angew. Chem. Int. Ed. 1998; 37: 2046 10g Hartwig JF. Acc. Chem. Res. 1998; 31: 852 10h Wolfe JP, Wagaw S, Marcoux J.-F, Buchwald SL. Acc. Chem. Res. 1998; 31: 805 For select examples, see: 11a Frederick MO, Mulder JA, Tracey MR, Hsung RP, Huang J, Kurtz KC. M, Shen L, Douglas CJ. J. Am. Chem. Soc. 2003; 125: 2368 11b Dunetz JR, Danheiser RL. Org. Lett. 2003; 5: 4011 11c Zhang Y, Hsung RP, Tracey MR, Kurtz KC. M, Vera EL. Org. Lett. 2004; 6: 1151 11d Hirano S, Tanaka R, Urabe H, Sato F. Org. Lett. 2004; 6: 727 11e Chen WY, Wang L, Frings M, Bolm C. Org. Lett. 2014; 16: 3796 11f Zhang X, Zhang Y, Huang J, Hsung RP, Kurtz KC. M, Oppenheimer J, Petersen ME, Sagamanova IK, Shen L, Tracey MR. J. Org. Chem. 2006; 71: 4170 12 For a leading reference on oligo(ortho-arylenes), see: Lehnherr D, Chen C, Pedramrazi Z, DeBlase CR, Alzola JM, Keresztes I, Lobkovsky EB, Crommie MF, Dichtel WR. Chem. Sci. 2016; 7: 6357 For select examples of palladium-catalyzed N-vinylation, see: 13a Lebedev AY, Izmer VV, Kazyul’kin DN, Beletskaya IP, Voskoboynikov AZ. Org. Lett. 2002; 4: 623 13b Barluenga J, Fernández MA, Aznar F, Valdés C. Chem. Commun. 2002; 2362 13c Kozawa Y, Mori M. Tetrahedron Lett. 2002; 43: 111 For select examples of copper-catalyzed vinylation, see: 13d Lam PY. S, Vincent G, Clark CG, Deudon S, Jadhav PK. Tetrahedron Lett. 2001; 42: 3415 13e Lam PY. S, Vincent G, Bonne D, Clark CG. Tetrahedron Lett. 2003; 44: 4927 13f Jiang L, Job GE, Klapars A, Buchwald SL. Org. Lett. 2003; 5: 3667 13g Pan X, Cai Q, Ma D. Org. Lett. 2004; 6: 1809 13h Taillefer M, Ouali A, Renard B, Spindler J.-F. Chem. Eur. J. 2006; 12: 5301 13i Liao Q, Wang Y, Zhang L, Xi C. J. Org. Chem. 2009; 74: 6371 For select examples of oxidative cross-coupling reactions, see: 14a Hamada T, Ye X, Stahl SS. J. Am. Chem. Soc. 2008; 130: 833 14b Jia W, Jiao N. Org. Lett. 2010; 12: 2000 14c Laouiti A, Rammah MM, Rammah MB, Marrot J, Couty F, Evano G. Org. Lett. 2012; 14: 6 15 Lamm AN, Liu S.-Y. Mol. BioSyst. 2009; 5: 1303 16 BN-Stilbene {1-[(E)-2-Phenylvinyl]-1,2-dihydro-1,2-azaborinine} (10) In a dry box, an oven-dried 50 mL round-bottomed flask was charged with 2-benzyl-1,2-dihydro-1,2-azaborinine (7)6 (507 mg, 3.00 mmol) and toluene (15 mL), and the mixture was cooled to –30 °C. A 2.5 M solution of BuLi in hexane (1.26 mL, 3.15 mmol) was added at –30 °C, and the resulting mixture was stirred for 20 min while it slowly warmed to RT. Pd2(dba)3 (55 mg, 0.060 mmol), QPhos (170 mg, 0.240 mmol), and β-bromostyrene (476 μL, 3.60 mmol) were added, and the mixture was stirred at 85 °C for 15 h. At the completion of the reaction, the mixture was cooled to RT, then passed through an Acrodisc using CH2Cl2 as solvent. The filtrate was concentrated under reduced pressure, and the crude product was purified by column chromatography (silica gel, 2–10% CH2Cl2–pentane) to give 8 as a white solid; yield: 497 mg (61%). FTIR (thin film): 3059, 3025, 1644, 1611, 1511, 1492, 1401, 1356, 1260, 1117, 1008, 801, 751, 693, 517 cm–1. 1H NMR (500 MHz, CD2Cl2): δ = 7.70 (d, J = 14.5 Hz, 1 H), 7.60–7.54 (m, 2 H), 7.48 (d, J = 7.5 Hz, 2 H), 7.41 (t, J = 7.0 Hz, 2 H), 7.34–7.29 (m, 3 H), 7.25–7.22 (m, 2 H), 7.18–7.16 (m, 1 H), 6.65 (d, J = 14.0 Hz, 1 H), 6.58 (d, J = 11.5 Hz, 1 H), 6.40 (t, J = 7.0 Hz, 1 H), 2.91 (s, 2 H). 11B NMR (160 MHz, CD2Cl2): δ = 37.9. 13C NMR (151 MHz, CD2Cl2): δ = 143.8, 143.0, 136.4, 134.1, 133.9, 131.0 (br), 129.7, 129.4, 128.9, 128.1, 126.8, 124.9, 121.5, 111.8, 27.6 (br). HRMS (DART-TOF): m/z [M + H]+ calcd for C19H19BN: 272.16105, found: 272.16078. In a dry box, an oven-dried 20 mL microwave vial was charged with 8 (360 mg, 1.33 mmol), dodecanol (346 mg, 1.86 mmol), CuBr (19 mg, 0.13 mmol), pyridine (214 μL, 2.66 mmol), di-tert-butyl peroxide (293 mL, 1.59 mmol), and toluene (13 mL), and the mixture was stirred at 90 °C for 1 h, then cooled to RT and the solvent was removed under reduced pressure. The crude oxidized product was purified by column chromatography (silica gel 2–50% Et2O–pentane) to isolate a mixture containing the desired product and other byproducts that was used directly to the next step. In a dry box, an oven-dried 25 mL round-bottomed flask was charged with the mixture of oxidized products and Et2O (10 mL), which was then cooled to –30 °C. LAH (15 mg, 0.40 mmol) was added at –30 °C, and the mixture was stirred for 30 min. A 2.0 M solution of HCl in Et2O (395 μL, 0.790 mmol) was added at –30 °C and the mixture was stirred for 30 min while it slowly warmed to RT. The solvent was removed under reduced pressure, and the crude product was purified by column chromatography (silica gel, 100% pentane to 2% Et2O–pentane) to give 10 as a white solid; yield: 91.3 mg (38% over two steps). FTIR (thin film): 3063, 3022, 2539, 1650, 1604, 1508, 1404, 1262, 1152, 973, 755, 693, 596 cm–1. 1H NMR (500 MHz, CD2Cl2): δ = 7.68–7.64 (m, 2 H), 7.48 (d, J = 14.5 Hz, 1 H), 7.45 (t, J = 8.5 Hz, 2 H), 7.35 (t, J = 7.5 Hz, 2 H), 7.26 (t, J = 7.5 Hz, 1 H), 6.97 (d, J = 10.5 Hz, 1 H), 6.79 (d, J = 14.5 Hz, 1 H), 6.51 (t, J = 6.5 Hz, 1 H), 5.82–4.60 (br, 1 H). 11B NMR (160 MHz, CD2Cl2): δ = 33.2 (d, J = 109 Hz). 13C NMR (151 MHz, CD2Cl2): δ = 144.4, 136.9, 136.4, 134.1, 131.4 (br), 129.3, 127.9, 126.7, 118.8, 113.3. HRMS (DART-TOF): m/z [M + H]+ calcd for C12H13BN: 182.11410, found: 182.11324. 17 Abbey ER, Zakharov LN, Liu S.-Y. J. Am. Chem. Soc. 2008; 130: 7250 18 The crystal structure of BN-stilbene 10 is disordered due to the apparent centrosymmetric nature of the molecule. Nevertheless, the planar geometry of the solid-state structure of 10 is clearly observed. 19 Goodman DW. Pharm. Ther. 2010; 35: 273 20 A similar effect has been reported for the 2,1-borazaronaphthalenes, see ref. 9a. Supplementary Material Supplementary Material Supporting Information
