2R-Substituted 1R,25-Dihydroxyvitamin D3 Analogues
J . Org. Chem., Vol. 66, No. 26, 2001 8769
(4S,5R)-5-(ter t-Bu tyld im eth ylsila n yloxy)-4-[(R)-1-(ter t-
bu tyld im eth ylsila n yloxy)a llyl]oct-7-yn n itr ile (35). Alco-
hol 32 (129 mg, 313 µmol) was converted to nitrile 35 (80.0
mg, 61%) according to the procedure described above for
2957, 1254, 1075, 926, 837, 776, 625 cm-1; 1H NMR (400 MHz,
CDCl3) δ 0.02 (s, 3H), 0.05 (s, 3H), 0.06 (s, 3H), 0.09 (s, 3H),
0.87 (t, 3H, J ) 7.2 Hz), 0.89 (s, 18H), 1.27 (m, 2H), 1.36 (m,
2H), 1.76 (ddt, 1H, J ) 4.0, 5.2, 6.0 Hz), 1.95 (t, 1H, J ) 2.8
Hz), 2.39 (ddd, 1H, J ) 2.8, 6.4, 17.6 Hz), 2.41 (ddd, 1H, J )
2.8, 6.4, 17.6 Hz), 3.99 (dt, 1H, J ) 4.0, 6.4 Hz), 4.12 (ddt, 1H,
J ) 6.0, 8.0, 1.2 Hz), 5.07 (dt, 1H, J ) 1.2, 10.4 Hz), 5.13 (dt,
1H, J ) 1.2, 17.2 Hz), 5.85 (ddd, 1H, J ) 8.0, 10.4, 17.2 Hz);
13C NMR (100 MHz, CDCl3) δ -4.7, -4.5, -4.2, -3.7, 14.4,
18.0, 18.1, 22.3, 25.8, 25.9, 26.0, 28.2, 49.2, 69.7, 71.6, 75.7,
82.3, 115.2, 140.5; HREIMS calcd for C19H37O2Si2 (M+) 353.2330,
found 353.2332.
converting 30 from 28. Data for 35: colorless oil; [R]20 +1.39
D
(c 1.15, CHCl3); IR (neat) 3314, 2932, 2247, 1256, 1078, 928,
837, 777, 635 cm-1; 1H NMR (400 MHz, CDCl3) δ 0.05 (s, 3H),
0.08 (s, 6H), 0.10 (s, 3H), 0.90 (s, 18H), 1.73 (m, 2H), 1.96 (q,
1H, J ) 6.4 Hz), 2.03 (t, 1H, J ) 2.4 Hz), 2.38 (ddd, 1H, J )
2.4, 6.0, 16.8 Hz), 2.43 (ddd, 1H, J ) 2.4, 4.8, 16.8 Hz), 2.50
(dt, 2H, J ) 4.0, 8.4 Hz), 3.88 (dt, 1H, J ) 4.8, 6.0 Hz), 4.18
(tt, 1H, J ) 1.2, 6.4 Hz), 5.19 (dt, 1H, J ) 1.2, 10.4 Hz), 5.25
(dt, 1H, J ) 1.2, 17.2 Hz), 5.80 (ddd, 1H, J ) 6.4, 10.4, 17.2
Hz); 13C NMR (100 MHz, CDCl3) δ -4.7, -4.6, -4.3, -4.2, 17.0,
18.0, 18.2, 22.4, 25.9, 26.0, 26.7, 48.3, 71.0, 71.1, 75.2, 80.5,
116.6, 120.4, 138.2; HREIMS calcd for C23H43O2NSi2 (M+)
421.2814, found 421.2794.
(5S,6R)-6-(ter t-Bu tyld im eth ylsila n yloxy)-5-[(R)-1-(ter t-
bu tyld im eth ylsila n yloxy)a llyl]n on -8-yn n itr ile (40). Al-
cohol 37 (470 mg, 1.10 mmol) was converted to nitrile 40 (400
mg, 83%) according to the procedure described above for
obtaining 30 from 28. Data for 40: colorless oil; [R]20 +2.21
D
(4S,5R)-5-(ter t-Bu tyld im eth ylsila n yloxy)-4-[(R)-1-(ter t-
bu tyld im eth ylsila n yloxy)a llyl]oct-7-yn a l (36). Nitrile 35
(80.0 mg, 190 µmol) was converted to aldehyde 36 (71.0 mg,
89%) according to the procedure described above for obtaining
(c 1.27, CHCl3); IR (neat) 3314, 2930, 2361, 1255, 1078, 928,
837, 777, 632 cm-1; 1H NMR (400 MHz, CDCl3) δ 0.05 (s, 3H),
0.06 (s, 3H), 0.72 (s, 3H), 0.09 (s, 3H), 0.89 (s, 18H), 1.43 (m,
2H), 1.73 (m, 3H), 1.99 (t, 1H, J ) 2.6 Hz), 2.28 (t, 2H, J ) 7.3
Hz), 2.39 (ddd, 2H, J ) 2.8, 6.4, 6.4 Hz), 3.88 (dt, 1H, J ) 2.8,
6.7 Hz), 4.18 (dd, 1H, J ) 5.8, 7.7 Hz), 5.14 (dt, 1H, J ) 1.2,
10.4 Hz), 5.19 (dt, 1H, J ) 1.2, 17.1 Hz), 5.80 (ddd, 1H, J )
7.0, 10.4, 17.1 Hz); 13C NMR (100 MHz, CDCl3) δ -4.7, -4.5,
-4.2, -3.8, 17.5, 18.1, 18.2, 25.1, 25.3, 25.86, 25.9, 26.4, 48.5,
70.6, 71.1, 75.5, 81.1, 116.2, 119.8, 139.2; HREIMS calcd for
31 from 30. Data for 36: colorless oil; [R]20 +3.22 (c 1.15,
D
CHCl3); IR (neat) 3314, 2932, 2712, 1728, 1256, 1078, 926, 837,
777, 635 cm-1; 1H NMR (400 MHz, CDCl3) δ 0.04 (s, 3H), 0.06
(s, 3H), 0.07 (s, 3H), 0.10 (s, 3H), 0.89 (s, 18H), 1.69 (m, 2H),
1.87 (ddt, 1H, J ) 5.2, 5.6, 6.0 Hz), 1.99 (t, 1H, J ) 2.8 Hz),
2.40 (ddd, 1H, J ) 2.8, 6.0, 17.2 Hz), 2.43 (ddd, 1H, J ) 2.8,
6.0, 17.2 Hz), 2.57 (ddd, 1H, J ) 2.0, 2.8, 6.0 Hz), 2.59 (ddd,
1H, J ) 2.0, 3.2, 6.0 Hz), 3.94 (dt, 1H, J ) 4.4, 6.0 Hz), 4.17
(ddt, 1H, J ) 1.6, 5.6, 6.8 Hz), 5.14 (dt, 1H, J ) 1.6, 10.4 Hz),
5.21 (dt, 1H, J ) 1.6, 17.2 Hz), 5.83 (ddd, 1H, J ) 6.8, 10.4,
17.2 Hz); 13C NMR (100 MHz, CDCl3) δ -4.7, -4.5, -4.2, -3.9,
18.2, 18.3, 25.9, 26.4, 30.9, 43.8, 48.4, 70.5, 71.4, 75.6, 81.2,
C
20H36O2NSi2 (M+ - tBu) 378.2285, found 378.2298.
(5S,6R)-6-(ter t-Bu tyld im eth ylsila n yloxy)-5-[(R)-1-(ter t-
bu tyld im eth ylsila n yloxy)a llyl]n on -9-yn a l (41). Nitrile 40
(400 mg, 920 µmol) was converted to aldehyde 41 (320 mg,
82%) according to the procedure described above for obtaining
31 from 30. Data for 41: colorless oil; [R]20 +6.30 (c 1.78,
D
116.1, 139.2, 203.0; HREIMS calcd for
424.2829, found 424.2829.
C
23H44O3Si2 (M+)
CHCl3); IR (neat) 3314, 2930, 2712, 2361, 1730, 1253, 1072,
924, 837, 775, 632 cm-1; 1H NMR (400 MHz, CDCl3) δ 0.04 (s,
3H), 0.06 (s, 3H), 0.07 (s, 3H), 0.10 (s, 3H), 0.830 (s, 9H), 0.833
(s, 9H), 1.3 (m, 2H), 1.69 (m, 2H), 1.82 (m, 1H), 1.96 (t, 1H,
J ) 2.4 Hz), 2.40 (ddd, 1H, J ) 2.8, 6.0, 17.2 Hz), 2.43 (ddd,
1H, J ) 2.8, 6.0, 17.2 Hz), 2.37 (m, 3H), 3.96 (m, 1H), 4.12
(dd, 1H, J ) 5.8, 7.0 Hz), 5.10 (dt, 1H, J ) 1.6, 10.4 Hz), 5.17
(dt, 1H, J ) 1.6, 16.5 Hz), 5.83 (ddd, 1H, J ) 7.3, 10.4, 16.5
Hz); 13C NMR (100 MHz, CDCl3) δ -4.6, -4.4, -4.2, -3.7,
18.09, 18.17, 25.4, 25.9, 26.3, 44.4, 49.0, 70.3, 71.2, 75.6, 81.5,
115.8, 139.8, 202.8; HREIMS calcd for C20H37O3Si2 (M+ - tBu)
381.2281, found 381.2278.
(4S,5R)-5-(ter t-Bu tyld im eth ylsila n yloxy)-4-[(R)-1-(ter t-
bu tyld im eth ylsila n yloxy)a llyl]oct-7-yn -1-ol (37). Aldehyde
36 (71.0 mg, 167 µmol) was converted to alcohol 37 (70.0 mg,
98%) according to the procedure described above for obtaining
32 from 31. Data for 37: colorless oil; [R]21 +10.26 (c 1.15,
D
CHCl3); IR (neat) 3340, 3314, 2932, 1254, 1067, 924, 837, 776,
1
635 cm-1; H NMR (400 MHz, CDCl3) δ 0.04 (s, 3H), 0.06 (s,
3H), 0.07 (s, 3H), 0.10 (s, 3H), 0.89 (s, 18H), 1.39 (m, 2H), 1.57
(bs, 1H), 1.66 (q, 2H, J ) 6.4 Hz), 1.85 (ddt, 1H, J ) 4.8, 5.2,
5.6 Hz), 1.98 (t, 1H, J ) 2.8 Hz), 2.39 (ddd, 1H, J ) 2.8, 6.4,
16.8 Hz), 2.43 (ddd, 1H, J ) 2.8, 6.4, 16.8 Hz), 3.61 (t, 2H,
J ) 6.4 Hz), 3.97 (dt, 1H, J ) 4.8, 6.4 Hz), 4.16 (ddt, 1H, J )
1.2, 5.6, 7.2 Hz), 5.12 (dt, 1H, J ) 1.2, 9.6 Hz), 5.17 (dt, 1H,
J ) 1.2, 16.8 Hz), 5.84 (ddd, 1H, J ) 7.2, 9.6, 16.8 Hz); 13C
NMR (100 MHz, CDCl3) δ -4.8, -4.6, -4.3, -4.1, 18.0, 18.2,
21.5, 25.8, 25.9, 26.1, 32.3, 48.6, 63.0, 70.2, 71.5, 75.7, 81.2,
115.7, 139.0; HREIMS calcd for C23H46O3Si2 (M+) 426.2985,
found 426.2977.
(5S,6R)-6-(ter t-Bu tyld im eth ylsila n yloxy)-5-[(R)-1-(ter t-
bu tyld im eth ylsila n yloxy)a llyl]n on -8-yn -1-ol (42). Alde-
hyde 41 (320 mg, 731 µmol) was reduced to alcohol 42 (300
mg, 93%) according to the procedure described above for
obtaining 32 from 31. Data for 42: colorless oil; [R]21 +8.56
D
(c 0.63, CHCl3); IR (neat) 3314, 2932, 2361, 1253, 1070, 924,
837, 775, 625 cm-1; 1H NMR (400 MHz, CDCl3) δ 0.04 (s, 3H),
0.06 (s, 3H), 0.07 (s, 3H), 0.10 (s, 3H), 0.89 (s, 18H), 1.37 (m,
2H), 1.54 (m, 2H), 1.78 (m, 1H), 1.97 (t, 1H, J ) 2.6 Hz), 2.39
(m, 2H), 3.61 (t, 2H, J ) 6.4 Hz), 3.97 (dt, 1H, J ) 6.2, 10.0
Hz), 4.13 (t, 1H, J ) 6.8 Hz), 5.09 (dt, 1H, J ) 1.2, 10.4 Hz),
5.16 (dt, 1H, J ) 1.2, 17.1 Hz), 5.84 (ddd, 1H, J ) 7.3, 10.4,
17.1 Hz); 13C NMR (100 MHz, CDCl3) δ -4.6, -4.4, -4.2, -3.7,
18.1, 18.2, 25.4, 25.7, 25.9, 26.0, 26.2, 33.3, 49.3, 63.0, 70.0,
71.5, 75.7, 82.0, 115.5, 140.3; HREIMS calcd for C24H48O3Si2
(M+) 440.3142, found 440.3148.
(3R,4S,5R)-3,5-Bis-(ter t-bu tyld im eth ylsila n yloxy)-4-[3-
(ter t-bu tyld im eth ylsila n yloxy)p r op yl]oct-1-en -7-yn e (38).
Alcohol 37 (60.0 mg, 141 µmol) was converted to silyl ether
38 (63.0 mg, 83%) according to the procedure described above
for obtaining 33 from 32. Data for 38: colorless oil; [R]25D +8.70
(c 1.15, CHCl3); IR (neat) 3316, 2932, 1256, 1102, 924, 837,
776, 633 cm-1; 1H NMR (400 MHz, CDCl3) δ 0.03 (s, 3H), 0.04
(s, 6H), 0.05 (s, 3H), 0.07 (s, 3H), 0.09 (s, 3H), 0.89 (s, 27H),
1.32 (m, 2H), 1.56 (m, 2H), 1.75 (ddt, 1H, J ) 4.0, 6.4, 6.8 Hz),
1.95 (t, 1H, J ) 2.8 Hz), 2.38 (ddd, 1H, J ) 2.8, 6.4, 16.8 Hz),
2.42 (ddd, 1H, J ) 2.8, 6.4, 16.8 Hz), 3.56 (t, 2H, J ) 6.8 Hz),
4.03 (dt, 1H, J ) 4.0, 6.0 Hz), 4.12 (dd, 1H, J ) 6.4, 7.6 Hz),
5.08 (d, 1H, J ) 10.0 Hz), 5.14 (d, 1H, J ) 17.2 Hz), 5.84 (ddd,
1H, J ) 7.6, 10.0, 17.2 Hz); 13C NMR (100 MHz, CDCl3) δ -5.3,
-4.6, -4.4, -4.1, -3.6, 18.1, 18.2, 22.1, 25.9, 26.0, 26.1, 32.6,
49.2, 63.6, 69.9, 71.5, 75.9, 82.1, 115.5, 140.4; HREIMS calcd
for C25H51O3Si3 (M+) 483.3146, found 483.3141.
(3R,4S,5R)-3,5-Bis-(ter t-bu tyld im eth ylsila n yloxy)-4-[4-
(ter t-bu tyld im eth ylsila n yloxy)bu tyl]oct-1-en -7-yn e (43).
Alcohol 42 (90.0 mg, 205 µmol) was converted to silyl ether
43 (105 mg, 93%) according to the procedure described above
for obtaining 33 from 32. Data for 43: colorless oil; [R]25D +7.58
(c 1.29, CHCl3); IR (neat) 3316, 2930, 2359, 1253, 1100, 924,
837, 775, 630 cm-1; 1H NMR (400 MHz, CDCl3) δ 0.02 (s, 3H),
0.04 (s, 6H), 0.05 (s, 3H), 0.06 (s, 3H), 0.09 (s, 3H), 0.844 (s,
9H), 0.848 (s, 9H), 0.850 (s, 9H), 1.32 (m, 2H), 1.48 (m, 2H),
1.75 (m, 1H), 1.95 (t, 1H, J ) 2.5 Hz), 2.39 (dd, 2H, J ) 2.5,
6.4 Hz), 2.42 (t, 1H, J ) 6.4 Hz), 3.58 (t, 2H, J ) 6.4 Hz), 4.03
(dt, 1H, J ) 6.4, 10.0 Hz), 4.13 (dd, 1H, J ) 5.5, 7.3 Hz), 5.08
(dt, 1H, J ) 1.2, 10.0 Hz), 5.14 (dt, 1H, J ) 1.2, 17.2 Hz), 5.80
(ddd, 1H, J ) 7.6, 10.0, 17.2 Hz); 13C NMR (100 MHz, CDCl3)
(3R,4S,5R)-3,5-Bis(ter t-bu tyldim eth ylsilan yloxy)-4-pr o-
p yl-oct-1-en -7-yn e (39). Alcohol 37 (70.0 mg, 164 µmol) was
converted to enyne 39 (54.0 mg, 80%) according to the
procedure described above for obtaining 34 from 32. Data for
39: colorless oil; [R]22D +19.39 (c 1.15, CHCl3); IR (neat) 3316,