CHART I 4.2.2.2 Results Synthesis
4.2.2.6 Experimental Part
General. NMR spectra were obtained at 128 MHz (11B), 100 MHz (13C), and 400
174
MHz (1H) in CDCl3 or CD3CN. Chemical shifts were referenced to the solvent (1H,
13C) or to an external sample of B(OH)3 in MeOH (11B, = 18.1 ppm). Optical microscopy and phase identification were performed using a PZO “Biopolar”
polarized microscope equipped with a HCS400 Instec hot stage. Thermal anal ysis was obtained using a TA Instruments 2920 DSC. Transition temperatures and enthalpies were typically obtained using small samples (~0.5 mg) and a heating rate of 5 K min-
1.
Preparation of Esters 4[n]. General procedure.
Method A. Esters of phenols. The sulfonium acid (0.16 mmol) was suspended in CH2Cl2 (1 mL) and was treated with (COCl)2 (3 eq) and anhydrous DMF (catalytic amount). The suspension began to bubble and became homogenous and was stirred vigorously for 30 min at rt. The light yellow solution was evaporated to dryness. The residue was redissolved in anhydrous CH2Cl2 (1 mL) and the appropriate phenol 10 (1.1 eq) and freshly distilled NEt3 (3 eq) were added. The mixture was stirred at rt overnight.
The reaction mixture was washed with 5% HCl, dried (Na2SO4) and evaporated to dryness. The product was isolated by column chromatography (SiO2), the eluent was filtered through a cotton plug and the solvent evaporated to give the desired ester in about 60% yield. The resulting esters were purified further by repeated recrystallization.
Method B. Esters of cyclohexanols. The acid chloride derived from the sulfonium acid was generated as in Method A. The crude acid chloride, excess alcohol 11 (5 eq), and freshly distilled pyridine (5 eq) were stirred and heated for 3 days at 90 °C, protected from moisture. At times, the reaction was cooled to rt, and minimal amount of anhydrous
175
CH2Cl2 was added to wash the sides of the flask. The product was purified as in Method A.
* NMR spectra of all esters 4[n] recorded at ambient temperature show the presence of minor quantities (about 20%) of the cis isomer, (4[n]-cis) with characteristic signals at 2.08-2.15 (m), 2.28-2.35 (m) and 3.55-3.65 (m) ppm in the 1H NMR spectra. The B(10) signals of the cis isomers are shifted upfield by about 1 ppm relative to the trans isomers in 11B NMR spectra. In addition, in compounds 4[n]h the pyrimidine ring of the cis isomer is shifted downfield by about 0.01 ppm relative to the trans isomer 4[n]h-trans.
Ester 4[3]c.
The ester was obtained in 65% yield, purified by column chromatography (CH2Cl2/hexane, 1:3) followed by recrystallization from iso-octane/toluene (2x) and then methanol/water (2x) to give a white crystalline solid: 1H NMR (400 MHz, CDCl3) 0.6- 2.8 (br m, 8H), 0.96 (t, J = 5.6 Hz, 3H), 1.39-1.43 (m, 5H), 1.67-1.79 (m, 2H), 2.38 (br d, J = 11.6 Hz, 2H), 3.44 (br t, J = 10.4, 2H), 3.72 (br d, J = 10.0 Hz, 2H), 7.29 (d, J = 6.8 Hz, 2H), 7.37-7.40 (m, 2H); {1H}11B NMR (128 MHz, CDCl3) -19.6 (4B), -14.0 (4B), 32.0 (1B). Anal. Calcd. for C17H28B9F3O3S: C, 43.75; H, 6.05. Found: C, 43.94; H, 6.07.
Ester 4[3]d.
176
The ester was obtained in 58% yield, purified by column chromatography (CH2Cl2) followed by recrystallization from iso-octane/toluene (2x) and then methanol/water (2x) to give a white crystalline solid: 1H NMR (400 MHz, CDCl3) 0.6- 2.8 (br m, 8H), 0.96 (t, J = 5.6 Hz, 3H), 1.39-1.43 (m, 5H), 1.67-1.79 (m, 2H), 2.33 (br d, J = 11.2 Hz, 2H), 3.44 (br t, J = 10.4 Hz, 2H), 3.71 (br d, J = 10.8 Hz, 2H), 7.07 (t, J = 5.6 Hz, 2H); {1H}11B NMR (128 MHz, CDCl3) -19.6 (4B), -13.9 (4B), 32.4 (1B). Anal.
Calcd. for C16H26B9F3O2S: C, 44.00; H, 6.00. Found: C, 44.03; H, 6.07.
Ester 4[3]e.
The ester was obtained in 77% yield, purified by column chromatography (CH2Cl2/hexane, 1:2) followed by recrystallization from iso-octane/toluene (2x) to give a white crystalline solid: 1H NMR (400 MHz, CDCl3) 0.6-2.8 (br m, 8H), (t, J = 5.8 Hz, 3H),0.96 (t, J = 5.6 Hz, 3H), 1.05-1.12 (m, 2H), 1.18-1.23 (m, 2H), 1.28-1.32 (m, 3H), 1.39-1.43 (m, 5H), 1.47-1.59 (m, 2H), 1.67-1.79 (m, 2H), 1.83 (br d, J = 10.4 Hz, 2H), 2.18 (d, J = 8.4 Hz, 2H), 2.33 (br d, J = 11.2 Hz, 2H), 3.44 (br t, J = 10.4 Hz, 2H), 3.71 (br d, J = 10.8 Hz, 2H), 4.98-5.06 (m, 1H); {1H}11B NMR (128 MHz, CDCl3) -
(4B)- (4B) (1B). Anal. Calcd. for C19H41B9O2S: C, 52.96; H, 9.59.
Found: C, 53.24; H, 9.72.
Ester 4[3]f.
177
The ester was prepared by method B in 59% yield, purified by column chromatography (CH2Cl2) followed by recrystallization from iso-octane/toluene (2x) to give a white crystalline solid: 1H NMR (400 MHz, CDCl3) 0.6-2.8 (br m, 8H), (t, J
= 7.12 Hz, 3H),0.95 (t, J = 6.7 Hz, 3H), 1.04-1.13 (m, 2H), 1.15-1.30 (m, 7H), 1.35-1.43 (m, 5H), 1.45-1.59 (m, 2H), 1.64-1.76 (m, 2H), 1.84 (d, J = 12.9 Hz, 2H), 2.18 (d, J = 9.0 Hz, 2H), 2.33 (br d, J = 12.8 Hz, 2H), 3.41 (br t, J = 12.8 Hz, 2H), 3.69 (br d, J = 12.9 Hz, 2H), 4.98-5.06 (m, 1H); {1H}11B NMR (128 MHz, CDCl3) -(4B)-
(4B) (1B). Anal. Calcd. for C21H45B9O2S: C, 54.96; H, 9.88. Found: C, 55.08; H, 9.82.
Ester 4[3]g.
The ester was obtained in 64% yield, purified by column chromatography (CH2Cl2) followed by recrystallization from iso-octane/toluene (2x) and then CH3CN (2x) to give a white crystalline solid: 1H NMR (400 MHz, CDCl3) 0.6-2.8 (br m, 8H), 0.96 (t, J = 6.5 Hz, 3H), 1.41-1.42 (m, 5H), 1.67-1.77 (m, 2H), 2.36 (br d, J = 14.0 Hz, 2H), 3.44 (br t, J = 10.4 Hz, 2H), 3.72 (br d, J = 12.7 Hz, 2H), 7.21 (t, J = 7.6 Hz Hz, 2H), 7.43 (d, J = 8.6 Hz, 2H), 7.58 (d, J = 8.6 Hz, 2H); {1H} 11B NMR (128 MHz, CDCl3) - 19.6 (4B), -13.9 (4B), 32.0 (1B). Anal. Calcd. for C22H30B9F3O2S: C, 51.53; H, 5.90.
Found: C, 51.70; H, 6.00.
178 Ester 4[3]h.
The ester was obtained in 66% yield, purified by column chromatography (CH2Cl2/hexane, 2:1) followed by recrystallization from iso-octane/toluene (2x) to give a white crystalline solid: 1H NMR (400 MHz, CDCl3) 0.6-2.8 (br m, 8H), 0.89 (t, J = 6.9 Hz, 3H), 0.96 (t, J = 6.6 Hz, 3H), 1.25-1.45 (m, 9H), 1.65-1.79 (m, 6H), 2.41 (br d, J = 11.2 Hz, 2H), 2.69 (t, J = 7.8 Hz, 2H), 3.44 (br t, J = 10.4, 2H), 3.71 (br d, J = 10.8 Hz, 2H), 7.30 (t, J = 8.2 Hz, 2H), 8.36 (s, 2H); {1H}11B NMR (128 MHz, CDCl3) -
(4B)- (4B) (1B). Anal. Calcd. for C26H43B9N2O2S: C, 57.30; H, 7.95; N, 5.14. Found: C, 57.44; H, 8.07; N, 5.19.
Ester 4[3]i.
The ester was obtained in 88% yield, purified by column chromatography (CH2Cl2) followed by recrystallization from iso-octane/toluene (2x) and then methanol with few drops of acetone (2x) to give a white crystalline solid: 1H NMR (400 MHz, CDCl3) 0.6-2.8 (br m, 8H), 0.88 (t, J = 7.2 Hz, 3H), 0.96 (t, J = 6.5 Hz, 3H), 1.14-1.16 (m, 4H), 1.21-1.29 (m, 8H), 1.39-1.41 (m, 5H), 1.50-1.54 (m, 2H), 1.69-1.73 (m, 8H), 2.39 (br d, J = 12.9 Hz, 2H), 2.63 (t, J = 8.1 Hz, 2H), 3.43 (br t, J = 11.5 Hz, 2H), 3.73 (br d, J = 10.4 Hz, 2H), 6.98 (d, J = 8.1 Hz, 1H), 7.03 (d, J = 12.6 Hz, 1H), 7.23 (d, J =
179
8.1 Hz, 1H); {1H}11B NMR (128 MHz, CDCl3) -19.6 (4B), -13.9 (4B), 32.0 (1B). Anal.
Calcd. for C29H52B9FO2S: C, 59.94; H, 9.02. Found: C, 59.93; H, 8.91.
Ester 4[3]j.
The ester was obtained in 57% yield, purified by column chromatography (CH2Cl2) followed by recrystallization from iso-octane/toluene (2x) then CH3OH (2x) to give a white crystalline solid: 1H NMR (400 MHz, CDCl3) 0.6-2.8 (br m, 8H), 0.94 (t, J
= 6.8 Hz, 3H), 1.37-1.43 (m, 5H), 1.65-1.80 (m, 2H), 2.39 (br d, J = 12.2 Hz, 2H), 3.44 (br t, J = 12.8 Hz, 2H), 3.72 (br d, J = 12.6 Hz, 2H), 7.27 (s, 4H), 7.52 (d, J = 8.8 Hz, 2H), 8.29 (d, J = 8.8 Hz, 2H); {1H}11B NMR (128 MHz, CDCl3) -19.3 (4B), -13.7 (4B), 32.4 (1B). Anal. Calcd. for C24H32B9F3O5S: C, 49.12; H, 5.50. Found: C, 49.20; H, 5.51.
Ester 4[3]k.
The ester was prepared by method A in 66% yield, purified by column chromatography (CH2Cl2 then CH3CN) followed by recrystallization from hexane/ethyl acetate (2x) to give a white crystalline solid: 1H NMR (CD3CN, 400 MHz) 0.6-2.8 (br m, 8H) 0.94 (t, J = 6.8 Hz, 3H). 1.30-1.43 (m, 5H), 1.62-1.80 (m, 2H), 2.34 (br d, J = 11.9 Hz, 2H), 3.43 (br t, J = 12.0 Hz, 2H), 3.78 (d, J = 12.0 Hz, 2H), 7.36-7.45 (m, 6H), 8.27 (t, J = 8.6 Hz, 1H); 1H NMR (CDCl3, 400 MHz) 0.6-2.8 (br m, 8H) 0.96 (t, J = 6.5 Hz, 3H). 1.35-1.46 (m, 5H), 1.63-1.82 (m, 2H), 2.40 (d, J = 11.9 Hz, 2H), 3.44 (t, J =
- S
O
O
C3H7 O
O OCF3
180
12.9 Hz, 2H), 3.73 (d, J = 13.0 Hz, 2H), 7.28-7.36 (m, 6H), 8.20 (t, J = 8.4 Hz, 1H);
{1H}11B NMR (CD3CN, 128 MHz) --{1H} 11B NMR (CDCl3, 128 MHz) --. Anal. Calcd. for C24H31B9F4O5S:
C, 47.66; H, 5.17. Found: C, 47.61; H, 5.32.
Ester 4[3]l.
The ester was obtained in 61% yield, purified by column chromatography (CH2Cl2) followed by recrystallization from iso-octane/toluene (2x) and then CH3CN (2x) to give a white crystalline solid: 1H NMR (400 MHz, CDCl3) 0.6-2.8 (br m, 8H), 0.88 (t, J = 7.2 Hz, 3H), 0.96 (t, J = 6.5 Hz, 3H), 1.14-1.16 (m, 4H), 1.21-1.29 (m, 8H), 1.39-1.41 (m, 5H), 1.50-1.54 (m, 2H), 1.69-1.73 (m, 8H), 2.39 (br d, J = 12.9 Hz, 2H), 2.63 (t, J = 8.1 Hz, 2H), 3.43 (br t, J = 11.5 Hz, 2H), 3.73 (br d, J = 10.4 Hz, 2H), 6.99 (t, J = 7.4 Hz, 1H), 7.13 (t, J = 6.7 Hz, 1H), 7.42 (d, J = 7.6 Hz, 2H), 7.62 (d, J = 8.6 Hz, 2H); {1H}11B NMR (128 MHz, CDCl3) -19.5 (4B), -13.9 (4B), 32.1 (1B). Anal. Calcd.
for C35H55B9F2O2S: C, 62.26; H, 8.21. Found: C, 62.26; H, 8.11.
Ester 4[5]h.
The ester was obtained in 91% yield, purified by column chromatography (CH2Cl2) followed by recrystallization from hexane (2x) to give a white crystalline solid:
1H NMR (400 MHz, CDCl3) 0.6-2.8 (br m, 8H), 0.90 (t, J = 7.0 Hz, 3H), 0.92 (t, J =
- S
O
O C5H11
N N
C6H13
181
6.7 Hz, 3H), 1.30-1.40 (m, 13H), 1.67-1.77 (m, 6H), 2.40 (br d, J = 12.5 Hz, 2H), 2.69 (t, J = 7.5 Hz, 2H), 3.45 (br t, J = 13.2 Hz, 2H), 3.73 (br d, J = 12.5 Hz, 2H), 7.31 (d, J = 8.2 Hz, 2H), 8.35 (d, J = 8.2 Hz, 2H), 8.86 (s, 2H); {1H}11B NMR (128 MHz, CDCl3) -19.5 (4B), -13.8 (4B), 32.9 (1B). Anal. Calcd. for C28H47B9N2O2S: C, 58.69; H, 8.27; N, 4.89.
Found: C, 58.95; H, 8.19; N, 4.84.
Ester 4[7]b.
The ester was prepared in 81% yield, purified by column chromatography (CH2Cl2) followed by recrystallization from iso-octane/toluene (2x) and then CH3OH (2x) to give a white crystalline solid: 1H NMR (400 MHz, CDCl3) 0.6-2.8 (br m, 8H), 0.90 (t, J = 6.5 Hz, 3H), 0.99 (t, J = 7.4 Hz, 3H), 1.25-1.38 (m, 13H), 1.49-1.51 (m, 2H), 1.72-1.80 (m, 4H), 2.37 (br d, J = 12.5 Hz, 2H), 3.43 (br t, J = 11.3 Hz, 2H), 3.71 (br d, J
= 12.5 Hz, 2H), 3.98 (t, J = 6.5 Hz, 2H), 6.93 (d, J = 9.0 Hz, 2H), 7.23 (d, J = 9.0 Hz, 2H); {1H}11B NMR (128 MHz, CDCl3) -19.7 (4B), -14.2 (4B), 32.5 (1B). Anal. Calcd.
for C24H45B9O3S: C, 56.41; H, 8.88. Found: C, 56.84; H, 8.89.
Ester 4[7]c.
The ester was obtained in 79% yield, purified by column chromatography (CH2Cl2) followed by recrystallization from iso-octane/toluene (2x) and then CH3OH (2x) to give a white crystalline solid: 1H NMR (400 MHz, CDCl3) 0.6-2.8 (br m, 8H),
(t, J = 6.3 Hz, 3H), 1.30-1.39 (m, 11H), 1.70-1.77 (m, 4H), 2.49 (br d, J = 13.9 Hz,
- S
O
O C7H15
OC4H9
- S
O
O C7H15
OCF3
182
2H), 3.44 (br t, J = 13.0 Hz, 2H), 3.72 (br d, J = 12.4 Hz, 2H), 7.30 (d, J = 8.6 Hz, 2H), 7.39 (d, J = 9.0 Hz, 2H); {1H} 11B NMR (128 MHz, CDCl3) -19.7 (4B), -14.0 (4B), 32.4 (1B). Anal. Calcd. for C21H36B9F3O3S: C, 48.24; H, 6.94. Found: C, 47.39; H, 6.96.
Ester 4[7]h.
The ester was obtained in 63% yield, purified by column chromatography (CH2Cl2) followed by recrystallization from iso-octane/toluene (2x) and then CH3OH (2x) to give a white crystalline solid: 1H NMR (400 MHz, CDCl3) 0.6-2.8 (br m, 8H), 0.87-0.92 (m, 6H), 1.25-1.38 (m, 17H), 1.62-1.77 (m, 6H), 2.39 (br d, J = 12.6 Hz, 2H), 2.68 (t, J = 7.6 Hz, 2H), 3.44 (br t, J = 13.1 Hz, 2H), 3.72 (br d, J = 12.9 Hz, 2H), 7.31 (d, J = 8.2 Hz, 2H), 8.35 (d, J = 8.2 Hz, 2H), 8.86 (s, 2H); {1H} 11B NMR (128 MHz, CDCl3) -19.5 (4B), -13.8 (4B), 32.8 (1B). Anal. Calcd. for C30H51B9N2O2S: C, 59.95; H, 8.55; N, 4.66. Found: C, 59.66; H, 8.41; N, 4.59.
Preparation of ester 4[7]j.
The ester was prepared by method A in 82% yield, purified by column chromatography (CH2Cl2) followed by recrystallization from iso-octane/toluene (2x) and then CH3OH (2x) to give a white crystalline solid: 1H NMR (400 MHz, CDCl3) 0.6-2.8 (br m, 8H), (t, J = 6.6 Hz, 3H), 1.30-1.39 (m, 11H), 1.70-1.77 (m, 4H), 2.49 (br d, J
= 14.2 Hz, 2H), 3.44 (br t, J = 12.7 Hz, 2H), 3.71 (br d, J = 12.0 Hz, 2H), 7.29 (s, 4H),
- S
O
O C7H15
N N
C6H13
- S
O
O
C7H15 O
O OCF3
183
7.52 (d, J = 8.7 Hz, 2H). 8.29 (d, J = 8.7 Hz, 2H); {1H} 11B NMR (128 MHz, CDCl3) -
(4B)-(4B) (1B). Anal. Calcd. for C28H40B9F3O5S: C, 52.31; H, 6.27.
Found: C, 52.48; H, 6.36.
Intermediates Preparation of 1,5-dibromo-3-heptylpentane (8[7]).2
Following a general literature procedure,3 a biphasic mixture of the 3- heptylpentane-1,5-diol, 47% aqueous HBr (15 eq) and an equal volume of conc. H2SO4 (relative to HBr) was stirred at 120 °C overnight. The black reaction mixture was cooled to rt, diluted by the addition of half its volume of H2O and extracted with CH2Cl2. The organic layers were combined, dried (MgSO4) and evaporated to leave black oil. The oil was passed through a short silica gel plug (hexanes) to give crude dibromide 8[7] as a slightly brown oil. The dibromide was purified further by short-path distillation (135 °C, 0.7 mmHg) to give 15.4 g (54% yield) of 8[7] as a colorless oil: 1H NMR (400 MHz, CDCl3) 0.88 (t, J = 7.0 Hz, 3H), 1.27 (m, 12H), 1.71-1.74 (m, 1H), 1.77-1.90 (m, 4H), 3.41 (t, J = 7.3 Hz, 4H); 13C NMR (100 MHz, CDCl3) 14.0, 22.6, 26.0, 29.2, 29.7, 31.2 (2C), 31.8, 32.4, 35.4, 36.6 (2C). Anal. Calcd. for C14H24Br2: C, 43.93; H, 7.37. Found: C, 43.63; H, 7.38.
C7H15
Br Br