SI_revised

Transcription

1 Supporting Information Copper-Catalyzed Regio- and Stereoselective Aminoboration of Alkenylboronates Daiki ishikawa, Koji Hirano,* and Masahiro Miura* Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita, Osaka , Japan Contents Instrumentation and Chemicals Experimental Procedures Detailed Optimization Studies X-Ray Analysis Chiral HPLC Charts of Enantioenriched Products Characterization Data for Products S1 S2 S3 S5 S6 S11 S12 S13 S14 S15 S16 S54 Instrumentation and Chemicals 1 H, 13 C, and 11 B MR spectra were recorded at 400 MHz, 100 MHz, and 128 MHz, respectively, for C 6 D 6 solutions. HRMS data were obtained by APCI. TLC analyses were performed on commercial glass plates bearing 0.25-mm layer of Wako H 2 Silica gel 60F 254. H 2 silica gel (Wakogel, 50H 2 ) was used for column chromatography. Unless otherwise noted, materials obtained from commercial suppliers were used as received. Anhydrous THF was purchased and used out of the bottle without further purification. Anhydrous Cu(OAc) 2 was purchased from Wako. LiO-t-Bu and (R,R)-Ph-BPE were obtained from Aldrich. MeO-dppbz was synthesized according to the literature. 1 Alkenyl dan boronates 1a 1f were prepared from the corresponding terminal alkynes via hydroboration/condensation sequence. 2 The diboron reagent pinb Bpin was commercially available, and pinb Bdan was prepared by Suginome s original procedure. O-Benzoyl-,-diethylhydroxylamine 2c was prepared by the condensation of diethylhydroxylamine and benzoyl chloride. Others were readily accessible through the nucleophilic substitution of the 3 1 Ito, S.; Itoh, T.; akamura, M. Angew. Chem., Int. Ed. 2011, 50, ishikawa, D.; Hirano, K.; Miura, M. J. Am. Chem. Soc. 2015, 137, Iwadate,.; Suginome, M. J. Am. Chem. Soc. 2010, 132, S1

2 corresponding secondary amines with benzoyl peroxide. 4 nitrogen atmosphere. All reactions were carried out under 4 (a) Berman, A. M.; Johnson, J. S. J. Am. Chem. Soc. 2004, 126, (b) Berman, A. M.; J Johnson,. S. J. Org. Chem. 2006, 71, 219. S2

3 Experimental Procedures Typical Procedure for Copper-Catalyzed Aminoboration of Alkenyl dan Boronates. Synthesis of syn-3aa-o: Cu(OAc) 2 (4.5 mg, mmol), 1,3-bis(diphenylphosphino)propane (dppp, 10 mg, mmol), LiO-t-Bu (60 mg, 0.75 mmol), and bis(pinacolato)diboron (pinb-bpin, 95 mg, 0.38 mmol) were placed in a 20 ml two-necked reaction flask, which was filled with nitrogen by using the Schlenk technique. THF was then added to the flask, and the suspension was stirred for 15 min at ambient temperature. A solution of (E)-2-(oct-1-en-1-yl)-2,3-dihydro-1H-naphtho[1,8-de][1,3,2]diazaborinine (1a, 70 mg, 0.25 mmol) and O-benzoyl-,-dibenzylhydroxylamine (2a, 0.12 g, 0.38 mmol) in THF (1.0 ml) was added dropwise. The reaction solution was stirred at the same temperature for additional 4 h. The resulting mixture was filtered through a short pad of sodium sulfate and neutral alumina and then evaporated in vacuo. 1-Methylnaphthalene (ca. 25 mg) was added as an internal standard, and the resulting mixture was analyzed by 1 H MR in C 6 D 6 solution. The yield of,-dibenzyl-1-(1h-naphtho[1,8-de][1,3,2]diazaborinin-2(3h)-yl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxab orolan-2-yl)octan-1-amine (3aa) was estimated to be 82% by comparison with integrated intensity of 1-methylnaphthalene. After the above 1 H MR analysis, the volatiles were evaporated. To the residue in the flask, THF (1.6 ml), H 2 O (1.6 ml), and abo 3 OH 2 (0.20 g, 2.1 mmol) were sequentially added, and the resulting mixture was stirred for 7 h under air. The reaction was quenched with sat. a 2 S 2 O 3 aq. The mixture was extracted with Et 2 O three times, and the combined organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography on H 2 silica gel with hexane/ethyl acetate (5/1, v/v) to give (1R*,2R*)-1-(dibenzylamino)-1-(1H-naphtho[1,8-de][1,3,2]diazaborinin-2(3H)-yl)octan-2-ol (syn-3aa-o, 81 mg, 0.17 mmol) in 66% overall yield. X-ray quality crystals were grown from heptane/ethyl acetate. Synthesis of anti-3aa-o: Cu(OAc) 2 (4.5 mg, mmol), 1,2-bis{di(4-methoxyphenyl)phosphino}benzene (MeO-dppbz, 14 mg, mmol), LiO-t-Bu (60 mg, 0.75 mmol), and bis(pinacolato)diboron (pinb-bpin, 95 mg, 0.38 mmol) were placed in a 20 ml two-necked reaction flask, which was filled with nitrogen by using the Schlenk technique. 1,4-Dioxane was then added to the flask, and the suspension was stirred for 15 min at ambient temperature. A solution of (E)-2-(oct-1-en-1-yl)-2,3-dihydro-1H-naphtho[1,8-de][1,3,2]diazaborinine S3

4 (1a, 70 mg, 0.25 mmol) and O-benzoyl-,-dibenzylhydroxylamine (2a, 0.12 g, 0.38 mmol) in 1,4-dioxane (1.0 ml) was added dropwise. The reaction solution was stirred at the same temperature for additional 4 h. The resulting mixture was filtered through a short pad of sodium sulfate and neutral alumina and then evaporated in vacuo. 1-Methylnaphthalene (ca. 25 mg) was added as an internal standard, and the resulting mixture was analyzed by 1 H MR in C 6 D 6 solution. The yield of,-dibenzyl-1-(1h-naphtho[1,8-de][1,3,2]diazaborinin-2(3h)-yl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxab orolan-2-yl)octan-1-amine (3aa) and syn/anti selectivity were estimated to be 79% and 14:86, respectively, by comparison with integrated intensity of 1-methylnaphthalene. After the above 1 H MR analysis, the volatiles were evaporated. To the residue in the flask, THF (1.6 ml), H 2 O (1.6 ml), and abo 3 OH 2 (0.20 g, 2.1 mmol) were sequentially added at 0 C, and the resulting mixture was stirred for 8.5 h at the same temperature under air (Caution: anti-3aa was somewhat unstable under the oxidative conditions. Thus, longer reaction periods and higher reaction temperature caused the decomposition to lower the yield of anti-3aa-o). The reaction was quenched with sat. a 2 S 2 O 3 aq. The mixture was extracted with Et 2 O three times, and the combined organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography on H 2 silica gel with hexane/ethyl acetate (5/1 to 3/1, v/v) to give (1R*,2S*)-1-(dibenzylamino)-1-(1H-naphtho[1,8-de][1,3,2]diazaborinin-2(3H)-yl)octan-2-ol (anti-3aa-o, 43 mg, 0.09 mmol) in 36% overall yield. Synthesis of 3aa-B(dan): Cu(OAc) 2 (4.5 mg, mmol), 1,3-bis(diphenylphophino)propane (dppp, 10 mg, mmol), LiO-t-Bu (60 mg, 0.75 mmol), and 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-naphtho[1,8-de][1,3,2]diazaborinine (pinb-b(dan), 0.11 g, 0.38 mmol) were placed in a 20 ml two-necked reaction flask, which was filled with nitrogen by using the Schlenk technique. THF (0.50 ml) was then added to the flask, and the suspension was stirred for 15 min at ambient temperature. A solution of (E)-2-(oct-1-en-1-yl)-2,3-dihydro-1H-naphtho[1,8-de][1,3,2]diazaborinine (1a, 70 mg, 0.25 mmol) and O-benzoyl-,-dibenzylhydroxylamine (2a, 95 mg, 0.30 mmol) in THF (1.0 ml) was added dropwise. The solution was stirred at ambient temperature for additional 4 h. The resulting mixture was filtered through a short pad of sodium sulfate and neutral alumina. After evaporation of the volatile materials, the residue was purified by column chromatography on H 2 silica gel with hexane/ethyl acetate (5/1, v/v) to yield,-dibenzyl-1,2-bis(1h-naphtho[1,8-de][1,3,2]diazaborinin-2(3h)-yl)octan-1-amine (3aa-B(dan), 0.15 g, 0.24 mmol) in 94% yield. S4

5 Typical Procedure for Copper-Catalyzed Enantioselective Aminoboration of Alkenyl dan Boronates. Synthesis of optically active 3aa-O: Cu(OAc) 2 (4.5 mg, mmol), 1,2-bis((2R,5R)-2,5-diphenylphospholan-1-yl)ethane ((R,R)-Ph-BPE, 13 mg, mmol), LiO-t-Bu (60 mg, 0.75 mmol), and bis(pinacolato)diboron (pinb-bpin, 95 mg, 0.38 mmol) were placed in a 20 ml two-necked reaction flask, which was filled with nitrogen by using the Schlenk technique. THF was then added to the flask, and the suspension was stirred for 15 min at ambient temperature. A solution of (E)-2-(oct-1-en-1-yl)-2,3-dihydro-1H-naphtho[1,8-de][1,3,2]diazaborinine (1a, 70 mg, 0.25 mmol) and O-benzoyl-,-dibenzylhydroxylamine (2a, 0.12 g, 0.38 mmol) was added dropwise. The reaction solution was stirred at the same temperature for additional 4 h. The resulting mixture was filtered through a short pad of sodium sulfate and neutral alumina and then evaporated in vacuo. 1-Methylnaphthalene (ca. 25 mg) was added as an internal standard, and the resulting mixture was analyzed by 1 H MR in C 6 D 6 solution. The yield of,-dibenzyl-1-(1h-naphtho[1,8-de][1,3,2]diazaborinin-2(3h)-yl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxab orolan-2-yl)octan-1-amine (3aa) was estimated to be 77% by comparison with integrated intensity of 1-methylnaphthalene. After the above 1 H MR analysis, the volatiles were evaporated. To the residue in the flask, THF (1.5 ml), H 2 O (1.5 ml), and abo 3 OH 2 (0.19 g, 1.9 mmol) were sequentially added, and the resulting mixture was stirred for 7 h under air. The reaction was quenched with sat. a 2 S 2 O 3 aq. The mixture was extracted with Et 2 O three times, and the combined organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography on H 2 silica gel with hexane/ethyl acetate (5/1, v/v) to give 1-(dibenzylamino)-1-(1H-naphtho[1,8-de][1,3,2]diazaborinin-2(3H)-yl)octan-2-ol (3aa-O, 75 mg, 0.15 mmol) in 61% overall yield. The enantiomeric ratio was determined to be 88:12 by chiral HPLC analysis on a chiral stationary phase. S5

6 Detailed Optimization Studies Table S1. Optimization Studies 1: Ligand Effects with CuCl [a] C 6 H 13 1a B(dan) + pinb Bpin + BzO Bn 2 2a 10 mol % CuCl 10 mol % ligand LiO-t-Bu THF, rt, 4 h pinb B(dan) C 6 H 13 Bn 2 3aa entry ligand yield (%), syn/anti [b] entry ligand yield (%), syn/anti [b] 1 dppm 16, >99:1 16 (t-bu) 2 -dppbz 30, >99:1 2 dpppe 67, 84:16 17 TMS-dppbz 72, >99:1 3 dppp 72, 97:3 18 DTBM-dppbz 16, >99:1 4 dppb 16, >99:1 19 (Z)-Ph 2 PCH=CHPPh 2 73, 84:16 5 dpppen 82, 96:4 20 P(4-MeOC 6 H 4 ) 3 81, 74:26 6 [c] rac-binap 93, >99:1 21 P(2-MeOC 6 H 4 ) 3 76, >99:1 7 dppf 0, n.d. 22 P[2,6-(MeO) 2 C 6 H 3 ] 3 80, >99:1 8 xantphos 6, >99:1 23 P[2,4,6-(MeO) 3 C 6 H 2 ] 3 77, 98:2 9 dppbz 72, 27:73 24 P[3,5-Me 2-4-MeOC 6 H 2 ] 3 84, 76:24 10 CF 3 -dppbz 71, 29:71 25 P(2-MeC 6 H 4 ) 3 10, >99:1 11 (CF 3 ) 2 -dppbz 89, 80:20 26 IMes HCl 0, n.d. 12 F 3 -dppbz 54, 27:73 27 IPr HCl 0, n.d. 13 MeO-dppbz 85, 27:73 28 phen 51, >99:1 14 Me 2 -dppbz 51, 93:7 29 bpy 29, >99:1 15 t-bu-dppbz 71, 29:71 30 dmphen 55, >99:1 [a] Reaction conditions: CuCl (0.025 mmol), ligand (0.025 mmol for entries 1 19 and 26 30, mmol for entries 20 25), 1a (0.25 mmol), pinb Bpin (0.38 mmol), 2a (0.38 mmol), LiO-t-Bu (0.75 mmol), THF (1.5 ml), 2, rt, 4 h. [b] 1 H MR yields are shown. Syn/anti ratios are also determined by 1 H MR of the crude product. [c] Unfortunately, the CuCl/rac-binap system was too specific for the reaction of 1a with 2a. n.d. = not determined. S6

7 Ph 2 P npph 2 n = 1: dppm = 2: dppe = 3: dppp = 4: dppb = 5: dpppen Fe dppf PPh 2 PPh 2 O PPh 2 PPh 2 xantphos rac-binap PPh 2 PPh 2 phen ipr ipr + + bpy dmphen Cl IMes HCl Cl ipr ipr IPr HCl Ar = CF 3 F CF 3 F OMe PAr 2 dppbz CF 3 -dppbz CF 3 (CF 3 ) 2 -dppbz F F 3 -dppbz MeO-dppbz PAr 2 tbu SiMe 3 tbu Me 2 tbu OMe Me 2 -dppbz tbu-dppbz tbu (tbu) 2 -dppbz SiMe 3 TMS-dppbz tbu DTBM-dppbz S7

8 Table S2. Optimization Studies 2: Ligand Effects with Cu(OAc) 2 [a] C 6 H 13 1a B(dan) + pinb Bpin + BzO Bn 2 2a 10 mol % Cu(OAc) 2 10 mol % ligand LiO-t-Bu THF, rt, 4 h pinb B(dan) C 6 H 13 Bn 2 3aa entry ligand yield (%), syn/anti [b] entry ligand yield (%), syn/anti [b] 1 dppe 92, 93:7 9 t-bu-dppbz 72, 30:70 2 dppp 92, 99:1 10 TMS-dppbz 39, >99:1 3 dpppen 82, 93:7 11 P[3,5-(CF 3 ) 2 C 6 H 3 ] 3 19, >99:1 4 [c] rac-binap 90, >99:1 12 P[2,6-(MeO) 2 C 6 H 3 ] 3 53, >99:1 5 dppbz 84, 29:71 13 P[2,4,6-(MeO) 3 C 6 H 2 ] 3 70, 98:2 6 CF 3 -dppbz 91, 44:56 14 phen 54, >99:1 7 (CF 3 ) 2 -dppbz 94, 92:8 15 bpy 32, >99:1 8 MeO-dppbz 90, 28:72 16 dmphen 53, >99:1 [a] Reaction conditions: Cu(OAc) 2 (0.025 mmol), ligand (0.025 mmol for entries 1 10 and 14 16, mmol for entries 11 13), 1a (0.25 mmol), pinb Bpin (0.38 mmol), 2a (0.38 mmol), LiO-t-Bu (0.75 mmol), THF (1.5 ml), 2, rt, 4 h. [b] 1 H MR yields are shown. Syn/anti ratios are also determined by 1 H MR of the crude product. [c] Unfortunately, the CuCl/rac-binap system was too specific for the reaction of 1a with 2a. S8

9 Table S3. Optimization Studies 3: Solvent Effects with Cu(OAc) 2 /(CF 3 ) 2 -dppbz [a] C 6 H 13 1a B(dan) + pinb Bpin + BzO Bn 2 2a 10 mol % Cu(OAc) 2 10 mol % (CF 3 ) 2 -dppbz LiO-t-Bu solvent, rt, 4 h pinb B(dan) C 6 H 13 Bn 2 3aa entry solvent yield (%), syn/anti [b] entry solvent yield (%), syn/anti [b] 1 CPME 80, 46:54 4 t-butyl methyl ether 76, 34:66 2 1,4-dioxane 51, 76:24 5 toluene 52, 68:32 3 DME 86, 87:13 6 Cl(CH 2 ) 2 Cl trace, n.d. [a] Reaction conditions: Cu(OAc) 2 (0.025 mmol), (CF 3 ) 2 -dppbz (0.025 mmol), 1a (0.25 mmol), pinb Bpin (0.38 mmol), 2a (0.38 mmol), LiO-t-Bu (0.75 mmol), solvent (1.5 ml), 2, rt, 4 h. [b] 1 H MR yields are shown. Syn/anti ratios are also determined by 1 H MR of the crude product. n.d. = not determined. Table S4. Optimization Studies 4: Solvent Effects with Cu(OAc) 2 /MeO-dppbz [a] C 6 H 13 1a B(dan) + pinb Bpin + BzO Bn 2 2a 10 mol % Cu(OAc) 2 10 mol % MeO-dppbz LiO-t-Bu solvent, rt, 4 h pinb B(dan) C 6 H 13 Bn 2 3aa entry solvent yield (%), syn/anti [b] entry solvent yield (%), syn/anti [b] 1 CPME 95, 26:74 5 toluene 24, 15:85 2 1,4-dioxane 79, 14:86 6 Cl(CH 2 ) 2 Cl 58, 86:14 3 DME 90, 32:68 7 [c] CPME 42, 29:71 4 t-butyl methyl ether 33, 23:77 8 [c] 1,4-dioxane 89, 11:89 [a] Reaction conditions: Cu(OAc) 2 (0.025 mmol), MeO-dppbz (0.025 mmol), 1a (0.25 mmol), pinb Bpin (0.38 mmol), 2a (0.38 mmol), LiO-t-Bu (0.75 mmol), solvent (1.5 ml), 2, rt, 4 h. [b] 1 H MR yields are shown. Syn/anti ratios are also determined by 1 H MR of the crude product. [c] With PivO-Bn 2 (2a-Piv) instead of 2a. S9

10 Scheme S1. Effects of Substituents on Boron C 6 H 13 1a B(dan) + pinb Bpin BzO Bn 2 2a 10 mol % Cu(OAc) 2 10 mol % ligand LiO-t-Bu solvent, rt, 4 h pinb B(dan) C 6 H 13 Bn 2 3aa ligand solvent 1 H yield syn/anti dppp THF 92% 99:1 (CF 3 ) 2 -dppbz THF 94% 92:8 MeO-dppbz 1,4-dioxane 79% 14:86 Bpin C 6 H 13 1a-Bpin + pinb Bpin BzO Bn 2 2a 10 mol % Cu(OAc) 2 10 mol % ligand LiO-t-Bu solvent, rt, 4 h pinb Bpin C 6 H 13 Bn 2 3aa-Bpin ligand solvent 1 H yield syn/anti dppp THF 47% >99:1 (CF 3 ) 2 -dppbz THF 60% >99:1 MeO-dppbz 1,4-dioxane 62% >99:1 C 6 H 13 B(MIDA)+ 1a-B(MIDA) pinb Bpin BzO Bn 2 2a 10 mol % Cu(OAc) 2 10 mol % ligand LiO-t-Bu solvent, rt, 4 h pinb Bpin C 6 H 13 Bn 2 3aa-Bpin C 6 H 13 pinb B(MIDA) ligand solvent 1 H yield syn/anti dppp THF 30% >99:1 MeO-dppbz 1,4-dioxane 16% >99:1 Bn 2 3aa-B(MIDA) not detected B(dan) = H B H Bpin = O B O B(MIDA) = Me B O O O O S10

11 Table S5. Optimization Studies for Copper-Catalyzed Enantioselective Aminoboration of 1a with 2a [a] C 6 H 13 1a B(dan) + pinb Bpin BzO Bn 2 2a 10 mol % Cu(OAc) 2 10 mol % ligand LiO-t-Bu THF, rt, 4 h pinb B(dan) C 6 H * 13 * Bn 2 3aa abo 3 OH 2 THF/H 2 O rt, 7 h C 6 H 13 OH * * Bn 2 3aa-O B(dan) entry ligand yield of 3aa (%), syn/anti [b] yield of 3aa-O (%),er [c] 1 (S,S)-BDPP 90, 96:4 53, 38:62 2 (S,S)-Me-DuPhos 75, 20:80 n.d. 3 (R)-BIAP 84, 96:4 45, 41:59 4 (R)-DTBM-SEGPHOS 34, >99:1 21, 47:53 5 (R,R)-Ph-BPE 77, 87:13 61, 88:12 [a] Reaction conditions: Cu(OAc) 2 (0.025 mmol), ligand (0.025 mmol), 1a (0.25 mmol), pinb Bpin (0.38 mmol), 2a (0.38 mmol), LiO-t-Bu (0.75 mmol), THF (1.5 ml), 2, rt, 4 h. Oxidation conditions: abo 3 OH 2 (2.5 mmol), THF/H 2 O (1/1), open flask, 7 h [b] 1 H MR yields are shown. Syn/anti ratios are also determined by 1 H MR of the crude product. [c] Isolated overall yields of the syn isomer. The anti-isomer was somewhat unstable for the oxidative conditions with abo 3 OH 2. The er values are determined by HPLC analysis on a chiral stationary phase. n.d. = not determined. Ph 2 P PPh 2 (S,S)-BDPP Me Me P P Me Me (S,S)-Me-DuPhos Ph Ph P P Ph Ph (R,R)-Ph-BPE PPh 2 PPh 2 O O O PAr 2 PAr 2 Ar = t-bu OMe (R)-BIAP O (R)-DTBM-SEGPHOS t-bu S11

12 X-Ray Analysis 3aa-O grown from heptane/ethyl acetate Figure S1. ORTEP Drawing of 3aa-O (CCDC ) S12

13 3ah-B(dan) grown from heptane/dichloromethane Figure S2. ORTEP Drawing of 3ah-B(dan) (CCDC ) S13

14 Chiral HPLC Charts of Enantioenriched Products syn-3aa-o (61%): The enantiomeric ratio was determined by HPLC analysis in comparison with authentic racemic material (CHIRALPAK AD-H column, 80/20 n-hexane/2-propanol, 0.5 ml/min, major isomer: t R = 16.9 min, minor isomer: t R = 18.3 min, UV detection at nm, 30 o C.). rac-syn-3aa-o AU 分 Peak # Ret. Time Area Area % Optically active syn-3aa-o AU Peak # Ret. Time Area Area % S14

15 3ea-O (61%): The enantiomeric ratio was determined by HPLC analysis in comparison with authentic racemic material (CHIRALPAK AD-H column, 85/15 n-hexane/2-propanol, 0.5 ml/min, major isomer: t R = 46.8 min, minor isomer: t R = 37.1 min, UV detection at nm, 30 o C.). rac-3ea-o AU 分 Peak # Ret. Time Area Area % Optically active 3ea-O AU Peak # Ret. Time Area Area % S15

16 Characterization Data for Products 1 H, 13 C{ 1 H}, and 11 B MR spectra for all compounds are attached in the last part. (1R*,2R*)-1-(Dibenzylamino)-1-(1H-naphtho[1,8-de][1,3,2]diazaborinin-2(3H)-yl)octan-2-ol (syn-3aa-o) white solid; 111 o C- decomposition; 1 H MR (400 MHz, benzene-d 6 ) d 0.86 (t, J = 6.8 Hz, 3H), (m, 6H), (m, 3H), (m, 1H), 2.29 (d, J = 9.6 Hz, 1H), 3.41 (d, J = 13.6 Hz, 2H), 3.76 (dt, J = 2.8, 9.6 Hz, 1H), 3.84 (d, J = 13.6 Hz, 2H), 4.11 (bs, 1H), 5.35 (bs, 2H), 6.06 (dd, J = 2.0, 6.4 Hz, 2H), (m, 6H), (m, 4H), (m, 4H); 13 C MR (100 MHz, benzene-d 6 ) d 14.36, 23.11, 26.87, 29.93, 32.35, 36.17, (the boron-bound carbon, very weak), 57.26, 68.82, , , , , , , , , , ; 11 B MR (128 MHz, benzene-d 6 ) d 30.92; HRMS (APCI) m/z ([M+H] + ) calcd for C 32 H 39 B 3 O: , found: (1R*,2S*)-1-(Dibenzylamino)-1-(1H-naphtho[1,8-de][1,3,2]diazaborinin-2(3H)-yl)octan-2-ol (anti-3aa-o) colorless oil; 1 H MR (400 MHz, benzene-d 6 ) d 0.89 (t, J = 6.8 Hz, 3H), (m, 7H), (m, 1H), (m, 1H), (m, 1H), 2.15 (bs, 1H), 2.25 (d, J = 2.8 Hz, 1H), 3.54 (d, J = 14.0 Hz, 2H), 3.78 (d, J = 14.0 Hz, 2H), 4.01 (ddd, J = 2.8, 7.6, 7.6 Hz, 1H), 6.05 (dd, J = 1.6, 6.8 Hz, 2H), 6.06 (bs, 2H), (m, 6H), (m, 4H), (m, 4H); 13 C MR (100 MHz, benzene-d 6 ) d 14.35, 23.04, 26.94, 29.66, 32.28, 35.79, 57.78, 71.50, , , , , , , , , , The carbon signal bound to the boron was not observed due to quadrupolar relaxation.; 11 B MR (128 MHz, benzene-d 6 ) d 1.01; HRMS (APCI) m/z ([M+H] + ) calcd for C 32 H 39 B 3 O: , found: S16

17 (1R*,2R*)-1-(Dibenzylamino)-1-(1H-naphtho[1,8-de][1,3,2]diazaborinin-2(3H)-yl)-3-phenylpropa n-2-ol (3ba-O) white solid; 52 o C- decomposition; 1 H MR (400 MHz, benzene-d 6 ) d 2.28 (d, J = 8.8 Hz, 1H), 2.69 (dd, J = 3.2, 14.0 Hz, 1H), 2.81 (dd, J = 7.6, 14.0 Hz, 1H), 3.40 (d, J = 13.6 Hz, 2H), 3.78 (d, J = 13.6 Hz, 2H), (m, 2H), 5.27 (bs, 2H), 6.15 (dd, J = 2.4, 6.0 Hz, 2H), (m, 8H), (m, 5H), (m, 6H); 13 C MR (100 MHz, benzene-d 6 ) d 42.24, (the boron-bound carbon, very weak), 57.27, 70.91, , , , , , , , , , , , , , ; 11 B MR (128 MHz, benzene-d 6 ) d 30.28; HRMS (APCI) m/z ([M+H] + ) calcd for C 33 H 33 B 3 O: , found: (1R*,2R*)-1-(Diisopropylamino)-3-methyl-1-(1H-naphtho[1,8-de][1,3,2]diazaborinin-2(3H)-yl)but an-2-ol (3cb-O) white solid; m.p o C; 1 H MR (400 MHz, benzene-d 6 ) d 0.79 (d, J = 6.8 Hz, 6H), 0.99 (d, J = 6.8 Hz, 6H), 1.12 (d, J = 6.8 Hz, 3H), 1.23 (d, J = 6.8 Hz, 3H), (m, 1H), 1.98 (d, J = 10.8 Hz, 1H), 2.88 (q, J = 6.8 Hz, 1H), 2.89 (q, J = 6.8 Hz, 1H), 3.39 (dd, J = 3.2, 10.8 Hz, 1H), 4.44 (bs, 1H), 5.37 (bs, 2H), 6.05 (dd, J = 2.0, 6.4 Hz, 2H), (m, 4H); 13 C MR (100 MHz, benzene-d 6 ) d 16.47, 21.54, 21.74, 23.90, 32.16, 47.22, 71.15, , , , , , The carbon signal bound to the boron was not observed due to quadrupolar relaxation.; 11 B MR (128 MHz, benzene-d 6 ) d 30.91; HRMS (APCI) m/z ([M+H] + ) calcd for C 21 H 33 B 3 O: , found: (1R*,2R*)-1-Cyclohexyl-2-(dibenzylamino)-2-(1H-naphtho[1,8-de][1,3,2]diazaborinin-2(3H)-yl)et han-1-ol (3da-O) white solid; 107 o C- decomposition; 1 H MR (400 MHz, benzene-d 6 ) d (m, 3H), (m, 8H), 2.54 (d, J = 10.0 Hz, 1H), 3.37 (d, J = 13.6 Hz, 2H), 3.63 (dd, J = 3.2, 10.0 Hz, 1H), 3.87 (d, J = 13.6 Hz, 2H), 4.45 (bs, 1H), 5.34 (bs, 2H), 6.05 (dd, J = 1.2, 6.4 Hz, 2H), S17

18 (m, 6H), (m, 4H), 7.27 (d, J = 7.2 Hz, 4H); 13 C MR (100 MHz, benzene-d 6 ) d 26.62, (2C), 27.46, 31.44, 42.50, (the boron-bound carbon, very weak), 57.03, 72.33, , , , , , , , , , ; 11 B MR (128 MHz, benzene-d 6 ) d 30.74; HRMS (APCI) m/z ([M+H] + ) calcd for C 32 H 37 B 3 O: , found: (1R*,2R*)-6-Chloro-1-(dibenzylamino)-1-(1H-naphtho[1,8-de][1,3,2]diazaborinin-2(3H)-yl)hexan -2-ol (3ea-O) white solid; m.p o C; 1 H MR (400 MHz, benzene-d 6 ) d (m, 1H), (m, 1H), (m, 3H), (m, 1H), 2.21 (d, J = 9.6 Hz, 1H), 3.12 (t, J = 6.4 Hz, 2H), 3.37 (d, J = 13.6 Hz, 2H), 3.62 (dt, J = 2.8, 9.6 Hz, 1H), 3.80 (d, J = 13.6 Hz, 2H), 4.07 (bs, 1H), 5.32 (bs, 2H), 6.09 (dd, J = 2.0, 6.4 Hz, 2H), (m, 6H), (m, 4H), (m, 4H); 13 C MR (100 MHz, benzene-d 6 ) d 24.14, 32.87, 35.02, 45.06, (the boron-bound carbon, very weak), 57.23, 68.54, , , , , , , , , , ; 11 B MR (128 MHz, benzene-d 6 ) d 30.31; HRMS (APCI) m/z ([M+H] + ) calcd for C 30 H 34 BCl 3 O: , found: (1R*,2R*)-,-Dibenzyl-1,2-bis(1H-naphtho[1,8-de][1,3,2]diazaborinin-2(3H)-yl)octan-1-amine (3aa-B(dan)) white solid; 84 o C- decomposition; 1 H MR (400 MHz, benzene-d 6 ) d 0.81(t, J = 7.2 Hz, 3H), (m, 2H), (m, 9H), 2.22 (d, J = 12.0 Hz, 1H), 3.20 (d, J = 13.6 Hz, 2H), 3.74 (d, J = 13.6 Hz, 2H), 5.32 (bs, 2H), 5.51 (bs, 2H), (m, 4H), (m, 2H), (m, 8H), 7.21 (d, J = 4.4 Hz, 4H), 7.34 (d, J = 7.2 Hz, 4H); 13 C MR (100 MHz, benzene-d 6 ) d 14.32, 23.09, (the boron-bound carbon, very weak), 30.03, 30.25, 30.69, 32.09, (the boron-bound carbon, very weak), 57.17, , , , , , , , , , , , , , , , ; 11 B MR (128 MHz, benzene-d 6 ) d (2B); HRMS (APCI) m/z ([M+H] + ) calcd for C 42 H 46 B 2 5 : , found: S18

19 (1R*,2R*)-,-Diisopropyl-1,2-bis(1H-naphtho[1,8-de][1,3,2]diazaborinin-2(3H)-yl)octan-1-amin e (3ab-B(dan)) white solid; 145 o C- decomposition; 1 H MR (400 MHz, benzene-d 6 ) d (m, 16H), (m, 8H), (m, 2H), 1.99 (d, J = 10.4 Hz, 1H), 2.78 (quintet, J = 6.4 Hz, 1H), 2.80 (quintet, J = 6.4 Hz, 1H), 5.43 (bs, 2H), 5.51 (bs, 2H), (m, 4H), (m, 8H); 13 C MR (100 MHz, benzene-d 6 ) d 14.35, 21.87, 23.12, 23.83, 30.19, 30.52, 30.58, (the boron-bound carbon, very weak), 32.23, 47.12, (the boron-bound carbon, very weak), , , , , , , , , , , , ; 11 B MR (128 MHz, benzene-d 6 ) d (2B); HRMS (APCI) m/z ([M+H] + ) calcd for C 34 H 46 B 2 5 : , found: (1R*,2R*)-,-Diethyl-1,2-bis(1H-naphtho[1,8-de][1,3,2]diazaborinin-2(3H)-yl)octan-1-amine (3ac-B(dan)) colorless oil; 1 H MR (400 MHz, benzene-d 6 ) d 0.87 (t, J = 7.2 Hz, 3H), 0.93 (t, J = 6.8 Hz, 6H), (m, 1H), (m, 9H), (m, 1H), 2.10 (d, J = 7.2 Hz, 1H), 2.44 (dq, J = 6.8, 13.6 Hz, 2H), 2.50 (dq, J = 6.8, 13.6 Hz, 2H), 5.53 (bs, 2H), 5.74 (m, 2H), 6.01 (dd, J = 1.2, 6.8 Hz, 2H), 6.06 (dd, J = 2.4, 6.0 Hz, 2H), 7.02 (dd, J = 6.8, 8.0 Hz, 2H), (m, 6H); 13 C MR (100 MHz, benzene-d 6 ) d 12.21, 14.34, 23.13, (the boron-bound carbon, very weak), 29.44, 30.31, 30.51, 32.28, 45.08, (the boron-bound carbon, very weak), , , , , , , , , , , , ; 11 B MR (128 MHz, benzene-d 6 ) d (2B); HRMS (APCI) m/z ([M+H] + ) calcd for C 32 H 42 B 2 5 : , found: (1R*,2R*)--Benzyl--methyl-1,2-bis(1H-naphtho[1,8-de][1,3,2]diazaborinin-2(3H)-yl)octan-1-a mine (3ad-B(dan)) white solid; 68 o C- decomposition; 1 H MR (400 MHz, benzene-d 6 ) d 0.86 (t, J = 7.2 Hz, 3H), (m, 10H), (m, 1H), 1.89 (d, J = 7.2 Hz, 1H), 2.10 (s, 3H), 3.37 (d, J = S19

20 13.2 Hz, 1H), 3.49 (d, J = 13.2 Hz, 1H), 5.57 (bs, 2H), 5.64 (bs, 2H), 6.02 (dd, J = 0.8, 7.2 Hz, 2H), 6.08 (dd, J = 2.0, 6.4 Hz, 2H), (m, 9H), 7.22 (t, J = 7.2 Hz, 2H), 7.36 (d, J = 7.2 Hz, 2H); 13 C MR (100 MHz, benzene-d 6 ) d 14.33, 23.11, (the boron-bound carbon, very weak), 29.25, 30.22, 30.47, 32.26, 40.89, (the boron-bound carbon, very weak), 62.26, , , , , , , , , , , , , , , , ; 11 B MR (128 MHz, benzene-d 6 ) d (2B); HRMS (APCI) m/z ([M+H] + ) calcd for C 36 H 42 B 2 5 : , found: (1R*,2R*)-,-Diallyl-6-chloro-1,2-bis(1H-naphtho[1,8-de][1,3,2]diazaborinin-2(3H)-yl)hexan-1- amine (3ee-B(dan)) white solid; m.p o C; 1 H MR (400 MHz, benzene-d 6 ) d (m, 1H), (m, 1H), (m, 2H), (m, 3H), 2.25 (d, J = 3.6 Hz, 1H), 2.94 (dd, J = 7.6, 14.4 Hz, 2H), (m, 2H), 3.17 (dd, J = 4.8, 14.4 Hz, 2H), 5.06 (dd, J = 1.2, 10.2 Hz, 2H), 5.11 (dd, J = 1.2, 17.2 Hz, 2H), 5.53 (bs, 2H), 5.61 (bs, 2H), 5.80 (dddd, J = 4.8, 7.6, 10.2, 17.2 Hz, 2H), 6.10 (dd, J = 1.2, 6.8 Hz, 2H), 6.16 (dd, J = 4.0, 4.0 Hz, 2H), (m, 8H); 13 C MR (100 MHz, benzene-d 6 ) d 27.07, (the boron-bound carbon, very weak), 28.52, 32.88, 44.91, (the boron-bound carbon, very weak), 55.33, , , , , , , , , , , , , , ; 11 B MR (128 MHz, benzene-d 6 ) d (2B); HRMS (APCI) m/z ([M+H] + ) calcd for C 32 H 37 B 2 Cl 5 : , found: (1R*,2R*)--Butyl-1,2-bis(1H-naphtho[1,8-de][1,3,2]diazaborinin-2(3H)-yl)--(pent-4-en-1-yl)oct an-1-amine (3af-B(dan)) colorless oil; 1 H MR (400 MHz, benzene-d 6 ) d (m, 6H), (m, 15H), (m, 1H), (m, 1H), (m, 1H), (m, 2H), (m, 4H), (m, 2H), 5.57 (bs, 2H), (m, 1H), 5.73 (bs, 2H), (m, 2H), 6.09 (dd, J = 2.4, 5.6 Hz, 2H), (m, 8H); 13 C MR (100 MHz, benzene-d 6 ) d 14.32, 14.48, 14.51, 21.08, 21.11, 23.11, 26.58, (the boron-bound carbon, very weak), 29.63, 29.69, 29.72, S20

21 29.76, 30.31, 30.49, 31.96, 32.04, 32.27, 51.74, 51.76, 52.10, 52.32, (the boron-bound carbon, very weak), , , , , , , , , , , , , , , , ; 11 B MR (128 MHz, benzene-d 6 ) d (2B); HRMS (APCI) m/z ([M+H] + ) calcd for C 37 H 50 B 2 5 : , found: ,2'-((1R*,2R*)-1-(Piperidin-1-yl)octane-1,2-diyl)bis(2,3-dihydro-1H-naphtho[1,8-de][1,3,2]diaza borinine) (3ag-B(dan)) white solid; m.p o C; 1 H MR (400 MHz, benzene-d 6 ) d 0.88 (t, J = 6.4 Hz, 3H), (m, 12H), (m, 4H), (m, 1H), 1.77 (d, J = 6.0 Hz, 1H), (m, 4H), 5.58 (bs, 2H), 5.95 (d, J = 0.8, 7.2 Hz, 2H), 5.96 (bs, 2H), 6.07 (dd, J = 1.6, 6.4 Hz, 2H), 6.98 (dd, J = 7.2, 8.0 Hz, 2H), (m, 6H); 13 C MR (100 MHz, benzene-d 6 ) d 14.34, 23.12, 25.13, 27.18, 29.68, 30.24, 30.45, 32.26, 54.74,106.12, , , , , , , , , , , The carbon signal bound to the boron was not observed due to quadrupolar relaxation.; 11 B MR (128 MHz, benzene-d 6 ) d (2B); HRMS (APCI) m/z ([M+H] + ) calcd for C 33 H 42 B 2 5 : , found: ((1R*,2R*)-1,2-Bis(1H-naphtho[1,8-de][1,3,2]diazaborinin-2(3H)-yl)octyl)morpholine (3ah-B(dan)) white solid; 106 o C- decomposition; 1 H MR (400 MHz, benzene-d 6 ) d 0.88 (t, J = 6.8 Hz, 3H), (m, 10H), (m, 1H), 1.66 (d, J = 5.2 Hz, 1H), (m, 2H), (m, 2H), (m, 4H), 5.55 (bs, 2H), 5.68 (bs, 2H), 5.91 (dd, J = 0.8, 7.2 Hz, 2H), 6.00 (d, J = 1.2, 6.8 Hz, 2H), 6.97 (dd, J = 7.2, 8.0 Hz, 2H), (m, 6H); 13 C MR (100 MHz, benzene-d 6 ) d 14.33, 23.12, (the boron-bound carbon, very weak), 28.82, 30.23, 30.63, 32.31, 54.33, (the boron-bound carbon, very weak), 67.57, , , , , , , , , , , , ; 11 B MR (128 MHz, benzene-d 6 ) d (2B); HRMS (APCI) m/z ([M+H] + ) calcd for C 32 H 40 B 2 5 O: , found: S21

22 8-((1R*,2R*)-1,2-Bis(1H-naphtho[1,8-de][1,3,2]diazaborinin-2(3H)-yl)octyl)-1,4-dioxa-8-azaspiro[ 4.5]decane (3ai-B(dan)) white solid; 103 o C- decomposition; 1 H MR (400 MHz, benzene-d 6 ) d 0.87 (t, J = 7.2 Hz, 3H), (m, 10H), (m, 1H), (m, 5H), (m, 2H), 2.70 (m, 2H), (m, 4H), 5.65 (bs, 2H), 5.82 (bs, 2H), 5.92 (dd, J = 0.8, 7.2 Hz, 2H), 6.02 (dd, J = 1.2, 6.8 Hz, 2H), 6.96 (dd, J = 7.2, 8.0 Hz, 2H), (m, 6H); 13 C MR (100 MHz, benzene-d 6 ) d 14.35, 23.13, (the boron-bound carbon, very weak), 29.08, 30.22, 30.55, 32.27, 36.16, 51.64, (the boron-bound carbon, very weak), 64.29, , , , , , , , , , , , , ; 11 B MR (128 MHz, benzene-d 6 ) d (2B); HRMS (APCI) m/z ([M+H] + ) calcd for C 35 H 44 B 2 5 O 2 : , found: ,2'-((1R*,2R*)-1-(Azepan-1-yl)octane-1,2-diyl)bis(2,3-dihydro-1H-naphtho[1,8-de][1,3,2]diazabo rinine) (3aj-B(dan)) white solid; 106 o C- decomposition; 1 H MR (400 MHz, benzene-d 6 ) d 0.87 (t, J = 6.8 Hz, 3H), (m, 1H), (m, 9H), (m, 9H), 1.97 (d, J = 8.4 Hz, 1H), (m, 4H), 5.48 (bs, 2H), 5.92 (bs, 2H), 6.05 (dd, J = 1.2, 6.8 Hz, 2H), 6.15 (dd, J = 6.0, 6.0 Hz, 2H), 7.03 (dd, J = 6.8, 8.4 Hz, 2H), (m, 6H); 13 C MR (100 MHz, benzene-d 6 ) d 14.34, 23.11, 27.03, (the boron-bound carbon, very weak), 29.67, 29.85, 30.14, 30.29, 32.22, 55.49, (the boron-bound carbon, very weak), , , , , , , , , , , , ; 11 B MR (128 MHz, benzene-d 6 ) d (2B); HRMS (APCI) m/z ([M+H] + ) calcd for C 34 H 44 B 2 5 : , found: S22

23 [ 1 H, 13 C, and 11 B MR Spectra of syn-3aa-o] C 6 H 13 OH H B H Bn 2 syn-3aa-o ppm ppm S23

24 ppm S24

25 [ 1 H, 13 C, and 11 B MR Spectra of anti-3aa-o] C 6 H 13 OH H B H Bn 2 anti-3aa-o ppm ppm S25

26 ppm S26

27 [ 1 H, 13 C, and 11 B MR Spectra of 3ba-O] Ph OH H B H Bn 2 3ba-O ppm ppm S27

28 ppm S28

29 [ 1 H, 13 C, and 11 B MR Spectra of 3cb-O] OH H B H i-pr 2 3cb-O ppm ppm S29

30 ppm S30

31 [ 1 H, 13 C, and 11 B MR Spectra of 3da-O] OH H B H Bn 2 3da-O pentane ppm pentane ppm S31

32 ppm S32

33 [ 1 H, 13 C, and 11 B MR Spectra of 3ea-O] Cl OH H B H Bn 2 3ea-O ppm ppm S33

34 ppm S34

35 [ 1 H, 13 C, and 11 B MR Spectra of 3aa-B(dan)] H B H H C 6 H 13 B H Bn 2 3aa-B(dan) ppm ppm S35

36 ppm S36

37 [ 1 H, 13 C, and 11 B MR Spectra of 3ab-B(dan)] H B H H C 6 H 13 B H i-pr 2 3ab-B(dan) ppm ppm S37

38 ppm S38

39 [ 1 H, 13 C, and 11 B MR Spectra of 3ac-B(dan)] H B H H C 6 H 13 B Et 2 3ac-B(dan) H ppm ppm S39

40 ppm S40

41 [ 1 H, 13 C, and 11 B MR Spectra of 3ad-B(dan)] H H B H B C 6 H 13 H Me Bn 3ad-B(dan) ppm ppm S41

42 ppm S42

43 [ 1 H, 13 C, and 11 B MR Spectra of 3ee-B(dan)] H B Cl 4 H H B H 3ee-B(dan) ppm ppm S43

44 ppm S44

45 [ 1 H, 13 C, and 11 B MR Spectra of 3af-B(dan)] H H B H B C 6 H 13 H Bu 3af-B(dan) ppm ppm S45

46 ppm S46

47 [ 1 H, 13 C, and 11 B MR Spectra of 3ag-B(dan)] H C 6 H 13 B H H B H 3ag-B(dan) ppm ppm S47

48 ppm S48

49 [ 1 H, 13 C, and 11 B MR Spectra of 3ah-B(dan)] H C 6 H 13 H B H B H O 3ah-B(dan) ppm ppm S49

50 ppm S50

51 [ 1 H, 13 C, and 11 B MR Spectra of 3ai-B(dan)] H C 6 H 13 H B H B H O O 3ai-B(dan) ppm ppm S51

52 ppm S52

53 [ 1 H, 13 C, and 11 B MR Spectra of 3aj-B(dan)] H C 6 H 13 H B H B H 3aj-B(dan) ppm ppm S53

54 ppm S54