(S)-2,2´-bis(methoxymethoxy)-1,1´-binaphthalene (SI4). (S)-2,2´-Bis(methoxymethoxy)-1,1´-
binaphthalene was prepared following the procedure described in the literature with slight modifications, instead of using MOMBr, it was used MOMCl.30 NMR spectral data were in agreement with those reported in the literature.30
Silylated BINOL derivative (SI5a-b)
SI5a and SI5b were prepared from (S)-2,2´-bis(methoxymethoxy)-1,1´-binaphthalene with the
corresponding silanol derivative in two steps following a procedure described in the literature.31 Spectroscopic data for SI5a31and SI5b32 were in agreement with those reported in the literature.
25 Rueping, M.; Nachtsheim, B. J.; Koenigs, R. M.; Ieawsuwan, W. Chem. Eur. J. 2010, 16, 13116. 26 Sai, M.; Yamamoto, H. J. Am. Chem. Soc. 2015, 137, 7091.
27 Kaupmees, K.; Tolstoluzhsky, N.; Raja, S.; Rueping, M.; Leito, I. Angew. Chem. Int. Ed. 2013, 52, 11569. 28 Knipe, P. C.; Smith, M. D. Org. Biomol. Chem. 2014, 12, 5094.
29 Lalli, C.; van de Weghe, P. Chem. Commun. 2014, 50, 7495. 30 Wu, T. R.; Shen, L.; Chong, J. M. Org. Lett. 2004, 6, 2701.
31 Storer, R. I.; Diane, E. C., Yike, N.; MacMillan, D. W. C. J. Am. Chem. Soc. 2006, 128, 84. 32 Maruoka, K.; Itoh, T.; Araki, Y.; Shirasaka, T.; Yamamoto, H. Bull. Chem. Soc. Jpn. 1988, 61, 2975.
Experimental
137
SI5a: 1H NMR (300 MHz, CDCl3) δ 7.98 (s, 2H, Carom-H), 7.80-7.65 (m, 14H, Carom-H), 7.51-
7.28 (m, 24H, Carom-H), 5.36 (s, 2H, OH). 13
C NMR (75 MHz, CDCl3) δ 156.5 (Carom-OH), 142.1
(Carom-H), 136.3 (Carom-H), 134.7 (Carom), 134.2 (Carom), 129.5 (Carom-H), 129.2 (Carom), 129.0
(Carom-H), 128.2 (Carom-H), 127.8 (Carom-H), 123.9 (Carom-H), 123.8 (Carom-H), 123.6 (Carom), 110.6
(Carom).
(S)-3,3´-Dibromo-5,5ʹ,6,6ʹ,7,7ʹ,8,8ʹ-octahydro-[1,1ʹ-binaphthalene]-2,2ʹ-diol (SI6)
(S)-H8-Binol was synthesized following the procedure described in the literature.33 Spectroscopic
data for (S)-H8-binol were in agreement with those reported in the literature.25,34
SI6 was prepared following the reported procedure in the literature from (S)-H8-binol by a
bromination step.25 Spectroscopic data for SI6 were in agreement with those reported in the literature.25
(S)-3,3ʹ-Bis(triphenylsilyl)-5,5ʹ,6,6ʹ,7,7ʹ,8,8ʹ-octahydro-[1,1ʹbinaphthalene]2,2ʹ-diol (SI7)
SI7 was synthesized following a procedure described in the literature with slight modifications as
follows.35 SI6 (1g, 2.21 mmol, 1 eq) was dissolved in DMF (16 mL, 0.14M), imidazole (0.67 g,
33 Korostylev, A.; Tararov, V. I.; Fischer, C.; Monsees, A.; Börner, A. J. Org. Chem. 2004, 69, 3220. 34 The enantiomeric excess of (S)-H
8-Binol was calculated by HPLC analysis on chiral stationary phase using Chiralcel
OD-H column [n-hexane/ i-PrOH (95:5)]; flow rate 1.0 mL/min; τminor= 13.85 min, τmajor = 16.77 min (99% ee).
35 Sewgobind, N. V.; Wanner, M. J.; Ingemann, S.; de Gelder, R.; van Maarseveen, J. H.; Hiemstra, H. J. Org. Chem.
138
Chapter 5
9.9 mmol, 4.5 eq) and corresponding silyl chloride (4.1 g, 13.3 mmol, 6 eq) were added at room temperature. The mixture was stirred at room temperature for 72 h until all starting material was consumed (reaction monitored by TLC using hexanes/CH2Cl2 2.5:1). The reaction was quenched
with a saturated solution of Na2CO3 (10 mL). The aqueous layer was extracted with EtOAc
(3×10 mL) and combined organic extracts were washed with HCl (1M, 20 mL) and brine (20 mL). Organic layer was dried over Na2SO4 and filtered. After the removal of the solvent, the
residue was filtered through a small plug of silica gel (hexanes/EtOAc 19:1) obtaining a crude wich pure enough to perform the next step. To a solution of bromosilyl ether (1 g, 1.03 mmol, 1 eq) in dry THF (25 mL, 0.04M) was dropwise added tBuLi (1.6M in pentane) (3.9 mL, 6.2 mmol, 6 eq) over 10 min at 0 ºC. The mixture was stirred at room temperature for 5 h. Then, the mixture was cooled to 0 ºC and a saturated solution of NH4Cl (15 mL) was added dropwise to
quench the reaction. The mixture was extracted with CH2Cl2 (3×10 mL) and combined organic
extracts were washed with brine and dried over Na2SO4, filtered and the solvent was removed
under reduced pressure. The residue was purified by FC on silica gel (hexanes/EtOAc 19:1 to 8:2) to obtain SI7 (1.07 g, 1.32 mmol, 60% two steps). 1H NMR (300 MHz, CDCl3) δ 7.61-7.55
(m, 12H, Carom-H), 7.45-7.29 (m, 18H, Carom-H), 6.93 (s, 2H, Carom-H), 4.87 (s, 2H, 2×OH), 2.58
(bs, 4H, 2×CH2), 2.45-2.24 (m, 4H, 2×CH2), 1.77-1.61 (m, 8H, 4×CH2). 13
C NMR (75 MHz, CDCl3) δ 156.3 (Carom-O), 140.2 (Carom), 139.8 (Carom-H), 136.4 (Carom-H), 134.8 (Carom), 130.2
(Carom), 129.5 (Carom-H), 127.8 (Carom-H), 119.0 (Carom), 117.3 (Carom), 29.3 (CH2), 27.6 (CH2),
Experimental
139
1,1´-Spirobiindane-7,7´-derivatives
The spiroanalog of BINOL was prepared following the procedure available on the literature with some modifications.36
1,5-bis-m-anisyl-3-pentanone (SI8). A solution of m-anisaldehyde (367.2 mmol, 2.0 eq) and
acetone (183.6 mmol, 1 eq) in 25 mL of EtOH was added dropwise to a solution of 37.5 g of NaOH in 300 mL of 50% aqueous ethanol, stirring in a water bath at room temperature. The mixture was stirred for 2 h with mechanic stirring. Then CH2Cl2 was added and the aqueous layer
was extracted with CH2Cl2. The combined organic layers were washed with water, dried over
Na2SO4, filtered and the solvent was removed under reduced pressure. A solution of 1,5-bis-m-
anisyl-1,4-pentadien-3-one (53.5 mmol, 1 eq) in the minimum quantity of acetone was stirred with Ni Raney (2 eq) under an atmosphere of H2 (1 atm, balloon) at room temperature,
monitoring the reaction by TLC and adding more catalyst as necessary. After 16 h, the catalyst was filtered off, washed with acetone and the filtrate was evaporated under reduced pressure. The crude was obtained as a colorless oil wich was purificated by FC on silica (hexanes to hexanes/EtOAc 8:2) to obtain SI8 (21.4 mmol, 40%). 1H NMR (300 MHz, CDCl3) δ 7.25-7.19
(m, 2H, Carom-H), 6.80-6.76 (m, 6H, Carom-H), 3.79 (s, 6H, OCH3), 2.90 (t, J = 7.5 Hz, 4H, CH2),
2.71 (t, J = 7.5 Hz, 4H, CH2). 13C NMR (75 MHz, CDCl3) δ 209.0 (C=O), 159.7 (Carom-O), 142.6
(Carom), 129.4 (Carom-H), 120.6 (Carom-H), 114.1 (Carom-H), 111.4 (Carom-H), 55.1 (OCH3), 44.4
(O=CCH2), 29.7 (CH2).
4,4´-dibromo-7,7´-dimethoxy-1,1´-spirobiindane (SI9). SI8 (9.8 mmol, 1 eq) was dissolved in
the minimum quantity of CH2Cl2, pyridine (34.3 mmol, 3.5 eq) was added and the mixture was
140
Chapter 5
cooled to -10 ºC. A solution of bromine in CH2Cl2 (24.5 mmol, 2.5 eq, 10% v/v) was added
dropwise. After that, the reaction mixture was allowed to warm to room temperature and stirred until the starting material disappeared (1 day). The mixture was washed with aqueous NaHSO3 to
remove excess bromine, washed with diluted HCl and water and dried over Na2SO4, filtered and
concentrate under vacuum. The product solidified on standing and it was used without further purification. The crude (5.5 mmol, 1 eq) was stirred with 22 g of H3PO4 (PPA can be used as
well) at 105 ºC for 5.5 h. Due to the complex workup, low scale reaction is recommended. The crude was cooled to 0ºC and quenched with aqueous KOH solution and stirred for 10 minutes. The mixture was extracted with Et2O (3×30 mL) and then with CH2Cl2 (3×30 mL), the combined
organic extracts were dried over Na2SO4, filtered and concentrated under vacuum. The residue
was purified by FC on silica gel (hexanes/EtOAc 9:1) and SI9 was obtained (6.4 mmol, 65%). 1H NMR (300 MHz, CDCl3) δ 7.26 (d, J = 8.6 Hz, 2H, Carom-H), 6.52 (d, J = 8.6 Hz, 2H, Carom-H),
3.52 (s, 3H, OCH3), 3.12-2.89 (m, 4H, CH2), 2.37-2.27 (m, 2H, CH2), 2.20-2.12 (m, 2H, CH2). 13
C NMR (75 MHz, CDCl3) δ 155.6 (Carom-O), 144.8 (Carom), 138.2 (Carom), 130.3 (Carom-H),
110.8 (Carom-H), 110.5 (Carom-Br), 61.9 (Cspiro), 55.4 (OCH3), 37.9 (CH2), 33.2 (CH2).
rac-1,1´-Spirobiindane-7,7´–diol, (±)-SI10. In a dried flask a solution of SI9 (1.4 mmol, 1 eq) in THF (0.12M) was placed under Argon atmosphere. The solution was cooled to -78 ºC and treated with tBuLi 1.9M solution in pentane (5.6 mmol, 4 eq). After 1 h, the reaction mixture was quenched with EtOH and aqueous layer was extracted with CH2Cl2 (3×10 mL). Combined
organic layers were washed with water and dried over Na2SO4, filtered and the solvent was
removed under reduced pressure The residue was used in the next step without further purification. In a dried flask a solution of 7,7´-dimethoxy-1,1´-spirobiindane (1.96 mmol, 1 eq) in CH2Cl2 (0.22M) was cooled to -78 ºC, treated with BBr3 in CH2Cl2 (4.5 mmol, 2.3 eq) and
allowed to warm to room temperature for 16 h. The reaction mixture was diluted with CH2Cl2
and washed with water until washings had neutral pH. Organic layer was dried over Na2SO4,
filtered and evaporated. The residue was purified by FC on silica gel (hexane/EtOAc, 19:1 to 8:2) to give product (±)-SI10 (1.1 mmol, 81%). 1H NMR (300 MHz, CDCl3) δ 7.18 (t, J = 7.7 Hz, 2H,
Carom-H), 6.90 (d, J = 7.4 Hz, 2H, Carom-H), 6.68 (d, J = 8.0 Hz, 2H, Carom-H), 4.72 (s, 2H, OH),
3.09-2.98 (m, 4H, CH2), 2.36-2.14 (m, 4H, CH2). 13
Experimental
141
OH), 145.8 (Carom), 130.5 (Carom), 129.8 (Carom-H), 117.6 (Carom-H), 114.3 (Carom-H), 57.4 (Cspiro),
37.4 (CH2), 31.2 (CH2).
7,7´-Bis-(L-menthyloxy-carbonyloxy)-1,1´-spirobiindane (R)-SI11 and (S)-SI11
The resolution of rac-1,1´-spirobiindane-7,7´–diol (±)-SI10 was achieved using L-Menthyl chloroformate (1.9 mmol, 2.4 eq) which was added to a stirring solution of rac-1,1´- spirobiindane-7,7´–diol (±)-SI10 (0.8 mmol, 1 eq), Et3N (2.95 mmol, 3.7 eq) and DMAP (0.08
mmol, 10 mol%) in CH2Cl2 (0.1M) under Ar atmosphere. After stirring for 9 h at room
temperature the organic layer was washed with water, HCl and brine. The organic layer was dried with Na2SO4, evaporated and the residue was purified by FC on silica gel (hexane to
hexane/EtOAc 95:5) to give (R)-SI11 (0.44 mmol, 40%) and (S)-SI11 (0.46 mmol, 42%). Mixed fractions were gotten as well.
(R)-SI11: 1H NMR (300 MHz, CDCl3) δ 7.20 (t, J = 7.7 Hz, 2H, Carom-H), 7.09 (d, J = 7.7 Hz,
2H, Carom-H), 6.98 (d, J = 7.7 Hz, 2H, Carom-H), 4.33 (td, J = 10.8, 4.4 Hz, 2H, 2×CcyH), 3.17-
2.99 (m, 4H, 2×CcyH2), 2.46-2.33 (m, 2H, CcyH2), 2.32-2.19 (m, 2H, CcyH2), 1.95-1.20 (m, 14H,
2×CcyH + 6×CcyH2), 1.07-0.82 (m, 16H, 2×CcyH + 2×CH + 4×CH3), 0.71 (d, J = 6.9 Hz, 6H,
2×CH3). 13C NMR (75 MHz, CDCl3) δ 152.6 (C=O), 147.6 (Carom), 145.7 (Carom), 138.9 (Carom),
127.8 (Carom-H), 121.9 (Carom-H), 119.9 (Carom-H), 78.5 (OCH), 59.1 (Cspiro), 46.5 (CH), 40.2
(CcyH2), 38.8 (CcyH2), 34.0 (CcyH2), 31.2 (CcyH2), 31.1 (CH), 25.4 (CH), 23.0 (CcyH2), 21.9 (CH3), 20.7 (CH3), 16.1 (CH3). (S)-SI11: 1H NMR (300 MHz, CDCl3) δ 7.22 (t, J = 7.7 Hz, 2H, Carom-H), 7.12 (d, J = 7.7 Hz, 2H, Carom-H), 6.95 (d, J = 7.7 Hz, 2H, Carom-H), 4.39 (td, J = 10.9, 4.4 Hz, 2H, 2×Ccy-H), 3.14- 2.92 (m, 4H, 2×CcyH2), 2.37-1.17 (m, 18H, 4×CcyH + 6×CcyH2 + 2×CH), 1.01-0.83 (m, 12H, 4×CH3), 0.72 (d, J = 6.9 Hz, 6H, 2×CH3). 13C NMR (75 MHz, CDCl3) δ 153.0 (C=O), 147.4
142
Chapter 5
(OCH), 58.5 (Cspiro), 46.6 (CH), 40.3 (CcyH2), 38.3 (CcyH2), 33.9 (CcyH2), 31.1 (CcyH2), 30.9
(CH), 25.4 (CH), 22.9 (CcyH2), 21.8 (CH3), 20.6 (CH3), 15.9 (CH3).
(S)-(−)-1,1´-Spirobiindane-7,7´-diol, (S)-SI12. For the preparation of (S)-SI12, a solution of (S)- SI11 (0.32 mmol, 1 eq) and hydrazine hydrate (4.4 mmol, 6 eq) in THF (0.15M) were added. The
mixture was refluxed under Ar atmosphere for 2 h. The crude was diluted with CH2Cl2, washed
with diluted HCl, water and dried over Na2SO4, filtered and the solvent was removed under
reduced pressure. FC on silica gel (hexanes/EtOAc 19:1 to 8:2) afforded (S)-SI12 (0.18 mmol, 56%). 1H NMR (300 MHz, CDCl3) δ 7.18 (t, J = 7.6 Hz, 2H, Carom-H), 6.89 (d, J = 7.6 Hz, 2H,
Carom-H), 6.68 (d, J = 8.1 Hz, 2H, Carom-H), 4.57 (s, 2H, OH), 3.07-3.01 (m, 4H, CH2), 2.35-2.14
(m, 4H, CH2). 13
C NMR (75 MHz, CDCl3) δ 152.9 (Carom-O), 145.8 (Carom), 130.4 (Carom), 129.9
(Carom-H), 117.7 (Carom-H), 114.3 (Carom-H), 57.4 (Cspiro), 37.4 (CH2), 31.2 (CH2). [α]D 20
: -43.9 (c = 1.0, CH2Cl2). Literature value [α]D
20
: -32.7 (c = 1.0, CHCl3).
The opposite enantiomer was obtained following the same procedure described.
(S)-6,6´-bis(triphenylsilyl)-2,2´,3,3´-tetrahydro-1,1´-spirobiindane-7,7´-diol, (S)-SI13
(S)-6,6´-bis(triphenylsilyl)-2,2´,3,3´-tetrahydro-1,1´-spirobiindane-7,7´-diol (S)-SI13 was prepared through an ortho-bromination step of (S)-SI12 following a patented procedure with slight modifications as follows.37 To a solution of (S)-SI12 (0.16 mmol, 1 eq) and KHCO
3 (0.32
mmol, 2 eq) in CH2Cl2 (1.5 mL, 0.11M), N-bromo succinimide (0.33 mmol, 2.05 eq) was added
slowly at -20ºC. The reaction mixture was stirred for 20 h. The mixture was quenched with HCl (2M, 5 mL) and extracted with CH2Cl2 (3×5 mL). Combined organic layers were dried over
Na2SO4 and filtered. After removal of the solvent, the crude was filtered through a small plug of
37 Chipa, L.; Zambad, S. P.; Gupta, R.; Tuli, D.; Kasundra, A.; Munshi, S.; Siddiqui, M. A.; Bhattamisra, S. K.; Dutt, C.; Chauthaiwale, V. Pyrazole derivatives as thyroid receptor modulators and their preparation, pharmaceutical compositions and use in the treatment of diseases. International Patent WO 2008149379, July 02, 2008.
Experimental
143
silica and it was used in the next step without further purification. NMR spectral data were in agreement with those reported in the literature.38
(S)-SI13. Silylation and rearrangement step were developed following a procedure reported in
the literature.39. Spectroscopic data for (S)-SI13 were in agreement with those reported in the literature.391H NMR (300 MHz, CDCl3) δ 7.63-7.60 (m, 12H, Carom-H), 7.43-7.37 (m, 6H, Carom-
H), 7.32-7.27 (m, 12H, Carom-H), 7.12 (d, J = 7.4 Hz, 2H, Carom-H), 6.87 (d, J = 7.4 Hz, 2H, Carom-
H), 5.20 (s, 2H, 2×OH), 3.16-2.96 (m, 4H, 2×CH2), 2.40-2.22 (m, 4H, 2×CH2). 13
C NMR (75 MHz, CDCl3) δ 158.5 (Carom), 149.2 (Carom), 139.0 (Carom-H), 136.3 (Carom-H), 134.5 (Carom),
131.4 (Carom), 129.6 (Carom-H), 128.0 (Carom-H), 117.9 (Carom-H), 117.6 (Carom), 58.2 (Cspiro), 37.3
(CH2), 31.2 (CH2).
38 Gonzalez, A. Z.; Benitez, D.; Tkatchouk, E.; Goddard III, W. A.; Toste, F. D. J. Am. Chem. Soc. 2011, 133, 5500. 39 Xing, C.-H.; Liao Y.-X.; Zhang, Y.; Sabarova, D.; Bassous, M.; Hu, Q.-S. Eur. J. Org. Chem. 2012, 6, 1115.
144
Chapter 5
2.3.2 Synthesis of catalysts
Catalysts 3g-j
General Procedure G (GP-G) for the synthesis of catalysts 3g-j: Corresponding (S)-diol (0.5
mmol, 1 eq) was placed in a two-necked flask fitted with a reflux condenser under Argon atmosphere and was dissolved in dry CH2Cl2 (0.15M). Freshly distilled and dry Et3N (3.5 mmol,
7 eq) and POCl3 (0.75 mmol, 1.5 eq) respectively were added at 0ºC and the reaction mixture
was stirred for 5 min. DMAP (1 mmol, 2 eq) was added into the reaction mixture at 0ºC and it was stirred at room temperature for 2 h. Freshly distilled EtCN (0.15M) was added followed by corresponding sulfonamide (1.5 mmol, 3 eq) and the reaction was heated to 95ºC for 14 h. The mixture was cooled to room temperature and quenched with water (10 mL), stirred for 30 minutes and diluted with CH2Cl2. The organic layer was separated from the mixture and the
aqueous phase was extracted with CH2Cl2 (3×10 mL). The combined organic extracts were
washed with NaHCO3 sat. aq. (5 mL) and 5M HCl (3×5 mL). Combined organic extracts were
dried with Na2SO4, filtered and solvent was removed under reduced pressure. The residue was
purified by FC on silica gel (CH2Cl2 to CH2Cl2/MeOH 95:5). After purification, residue must be
cleaned with 5M HCl (5×5 mL) since no calcium ions are present during the synthetic steps, it is likely that N-triflylphosphoramides bound calcium cations from the silica gel used for the final column chromatography but they release it upon acidic washing.40 EDX measurements had been done to confirm that these highly acidic BrØnsted acids are free from any metal impurities.41 (3h)
was synthesized following a procedure in the literature.26
40 Hatano, M.; Moriyama, K.; Maki, T.; Ishihara, K. Angew. Chem. Int. Ed. 2010, 122, 3911. 41 Rueping, M.; Nachtsheim, B. J.; Koenigs, R. M.; Ieawsuwan, W. Chem. Eur. J. 2010, 16, 13116.
Experimental
145
1,1,1-trifluoro-N-((11bS)-4-oxido-2,6-bis(triphenylsilyl)dinaphtho[2,1-
d:1´,2´-f][1,3,2]dioxaphosphepin-4-yl)methanesulfonamide (3g).
Following GP-G, 3g was isolated as a white solid by FC on silica gel (314 mg, 0.31 mmol, 63%), starting from SI5a (400 mg, 0.5 mmol) in CH2Cl2
(2.6 mL) with Et3N (0.49 mL, 3.5 mmol), POCl3 (70 µL, 0.75 mmol), DMAP (122 mg, 1 mmol),
EtCN (2.6 mL) and NH2Tf (235 mg, 1.5 mmol). Rf= 0.33 (CH2Cl2/MeOH, 98:2). 1
H NMR (300 MHz, CDCl3) δ 8.35 (s, 1H, Carom-H), 8.13 (s, 1H, Carom-H), 7.93 (d, J = 8.1 Hz, 1H, Carom-H),
7.85-7.78 (m, 7H, Carom-H), 7.78-7.69 (m, 6H, Carom-H), 7.58-7.24 (m, 24H, Carom-H), 4.26 (s, 1H,
NH). 13C NMR (75 MHz, CDCl3) δ 142.7 (Carom-H), 142.1 (Carom-H), 136.9 (Carom-H), 136.6
(Carom-H), 134.3 (Carom), 133.3 (Carom), 133.2 (Carom), 131.1 (Carom), 131.0 (Carom), 129.9 (Carom-H),
129.5 (Carom-H), 128.9 (Carom-H), 128.8 (Carom-H), 128.2 (Carom-H), 127.9 (Carom-H), 127.7 (Carom-
H), 126.8 (Carom-H), 126.0 (Carom-H), 125.9 (Carom-H), 125.1 (Carom), 121.7 (Carom), 120.9 (Carom). 19
F NMR (282 MHz, CDCl3) δ -77.8. IR (CH2Cl2): 1430 (SO2 st as), 1190 (SO2 st sim), 1190
(P=O st)cm-1. HRMS: Calculated for [C57H40NO5PSF3Si2]
– : 994.1855 [M-H]–; found: 994.1848. M.p.: 160-162ºC (CH2Cl2). [α]D 20 : +175.4 (c = 1.0, CH2Cl2). N-((11bS)-2,6-bis(tert-butyldimethylsilyl)-4-oxidodinaphtho[2,1-d:1´,2´- f][1,3,2]dioxaphosphepin-4-yl)-1,1,1-trifluoromethanesulfonamide (3h). Following GP-G, 3j was isolated as a white solid by FC on silica gel (314 mg, 0.31 mmol, 52%), starting from SI5b (125 mg, 0.24 mmol) in CH2Cl2
(0.8 mL) with Et3N (0.23 mL, 1.7 mmol), POCl3 (33 µL, 0.36 mmol),
DMAP (58.6 mg, 1 mmol), EtCN (0.8 mL) and NH2Tf (111 mg, 0.72
mmol). Rf= 0.27 (CH2Cl2/MeOH, 92:8). 1
H NMR (300 MHz, CDCl3) δ 8.07 (d, J = 8.7 Hz, 2H,
Carom-H), 7.91 (dd, J = 8.3, 5.1 Hz, 2H, Carom-H), 7.47-7.35 (m, 2H, Carom-H), 7.25-7.17 (m, 2H,
Carom-H), 7.06-6.97 (m, 2H, Carom-H), 2.49 (s, 1H, NH), 0.81 (s, 9H, 3×CH3), 0.79 (s, 9H,
3×CH3), 0.61 (s, 3H, CH3), 0.49 (s, 3H, CH3), 0.48 (s, 3H, CH3), 0.39 (s, 3H, CH3). 13
C NMR (75 MHz, CDCl3) δ 151.5 (Carom), 151.4 (Carom), 151.2 (Carom), 151.1 (Carom), 138.6 (Carom-H), 133.8
(Carom), 133.7 (Carom), 130.8 (Carom), 130.7 (Carom), 129.1 (Carom), 129.0 (Carom), 128.8 (Carom),
128.7 (Carom), 128.5 (Carom-H), 128.4 (Carom-H), 127.1 (Carom-H), 126.9 (Carom-H), 126.8 (Carom-H),
126.7 (Carom-H), 125.4 (Carom-H), 125.3 (Carom-H), 121.6 (Carom), 121.0 (Carom), 26.9 (CH3), 26.9
(CH3), 17.8 (CH3), 17.7 (CH3), -3.3 (CH3), -3.8 (CH3), -4.4 (CH3), -4.8 (CH3). 19