10926
U. Jahn et al. / Tetrahedron 65 (2009) 10917–10929
(d, C3), 46.9 (d, C3*), 56.0 (t, C2), 56.7 (t, C2*), 57.4 (t, C5*), 58.6 (t,
C5), 59.8 (s, TMP–C(CH3)2), 60.07 (s, TMP–C(CH3)2), 60.10 (t,
PhCH2*), 60.6 (t, PhCH2), 76.6 (t, C6), 78.7 (t, C6*), 80.4 (s, C(CH3)3*),
80.8 (s, C(CH3)3), 127.0 (d, CHAr*), 127.1 (d, CHAr), 128.38 (d, CHAr*),
128.43 (d, CHAr),128.8 (d, CHAr*),128.9 (d, CHAr),139.3 (s, CAr*),139.5
(s, CAr), 172.7 (s, C]O), 174.0 (s, C]O*). Resonances marked with *
belong to 3,4-trans-6c.
1H, CHOTMP); 5.05 (m, 2H, CH]CH2); 5.71 (ddt, J¼6.5, 10.2, 17.6 Hz,
1H, CH]CH2); 7.12–7.23 (m, 5H, ArH). 13C NMR (100 MHz, CDCl3):
d¼17.3 (t, TMP–CCH2CH2), 20.2 (q, TMP–CH3), 20.4 (q, TMP–CH3), 32.9
(q, TMP–CH3), 33.5 (q, TMP–CH3), 40.4 (t, TMP–CCH2), 51.3 (q, OCH3),
54.7 (t, NCH2CHCO), 57.1 (t, NCH2CH]), 59.1 (t, PhCH2N), 59.6 (s,
TMP–C(CH3)2), 60.7 (s, TMP–C(CH3)2), 85.0 (d, CHOTMP), 117.8 (t,
CH]CH2), 127.1 (d, CHAr), 128.3 (d, CHAr), 129.1 (d, CHAr), 135.4 (d,
CH]CH2), 139.3 (s, CAr), 173.5 (s, C]O).
4.2.6. tert-Butyl
3-(N-allyl-N-benzylamino)-2-(2,2,6,6-tetramethyl
piperidin-1-yloxy)propanoate (5c). Colorless oil, for yields see
4.2.9. tert-Butyl 1-(1-phenylethyl)-4-[(2,2,6,6-tetramethylpiperidin-
1-yloxy)methyl]pyrrolidine-3-carboxylates (6e). Isolated after flash
chromatography (hexanes/EtOAc 50:1–7:1) as a pale yellow oil. For
yields and diastereomeric ratios see Table 3. [Rf (hexanes/EtOAc
10:1)¼0.19].
Table 2. [Rf (hexanes/EtOAc 20:1)¼0.41]. IR (film); v [cmꢁ1]: 3064
~
(w), 2975 (m), 2930 (m), 1734 (s), 1365 (s), 1154 (s), 741 (m), 699
(m). MS (ESI) m/z, (%): 453 (MþNaþ, 70), 431 (MþHþ, 100), 160 (70)
[CH2]N(All)Bnþ]. C26H42N2O3 (430.62): calcd C 72.52, H 9.83, N
6.51; found C 72.73, H 9.99, N 6.27. 1H NMR (400 MHz, CDCl3):
4.2.9.1. (1R,3S,4R)-6e and (1R,3R,4S)-6e. IR (film); v [cmꢁ1]:
~
d
¼1.01–1.09 (m, 12H, TMP–CH3); 1.21 (m, 2H, TMP–CH2), 1.35 (m,
4H, TMP–CH2); 1.43 (s, 9H, C(CH3)3); 2.74 (dd, J¼5.0, 12.4 Hz, 1H,
NCHHCHCO); 2.82 (m, 2H, NCHHCHCO, NCHHCH]); 3.02 (dd,
J¼5.9, 14.1 Hz, 1H, NCHHCH]); 3.43 (d, J¼13.5 Hz, 1H, PhCHHN);
3.62 (d, J¼13.5 Hz, 1H, PhCHHN); 4.21 (dd, J¼5.0, 9.9 Hz, 1H,
CHOTMP); 5.03 (m, 2H, CH]CH2); 5.74 (m, 1H, CH]CH2); 7.14–7.25
2973 (m), 2930 (m), 2780 (w, br), 1727 (s), 1367 (m), 1146 (s), 701
(m). MS (ESI) m/z, (%): 445 (MþHþ, 100). C27H44N2O3 (444.65):
calcd C 72.93, H 9.97, N 6.30; found 73.14, H 10.19, N 5.92. 1H NMR
(600 MHz, CDCl3):
d
¼0.98–1.17 (m, 24H, TMP–CH3, TMP–CH3*);
1.29 (m, 2H, TMP–CH2, TMP–CH2*); 1.37 (d, J¼6.6 Hz, 3H, CHCH3*);
1.39 (d, J¼6.6 Hz, 3H, CHCH3); 1.38–1.45 (m, 8H, TMP–CH2, TMP–
CH2*); 1.42 (s, 9H, C(CH3)3); 1.44 (s, 9H, C(CH3)3*); 1.52 (m, 2H,
TMP–CH2, TMP–CH2*); 2.41 (dd, J¼7.8, 9.0 Hz, 1H, H5); 2.56 (dd,
J¼6.5, 8.7 Hz, 1H, H5*); 2.58 (dd, J¼7.3, 9.9 Hz 1H, H2); 2.60 (m, 1H,
H4*); 2.68 (dd, J¼5.9, 8.7 Hz, 1H, H5*); 2.69 (m, 1H, H4); 2.73 (dd,
J¼7.9, 9.9 Hz 1H, H2); 2.73 (dd, J¼8.4, 9.7 Hz, 1H, H2*); 2.93 (ddd,
J¼7.3, 7.9, 10.0 Hz, 1H, H3); 2.93 (dd, J¼9.1, 9.7 Hz, 1H, H2*); 3.02
(ddd, J¼7.4, 8.4, 9.1 Hz, 1H, H3*); 3.16 (dd, J¼6.5, 9.0 Hz, 1H, H5);
3.31 (d, J¼6.6 Hz, 1H, CHCH3); 3.34 (d, J¼6.6 Hz, 1H, CHCH3*); 3.71
(dd, J¼5.5, 8.4 Hz, 1H, H6*); 3.73 (dd, J¼6.1, 8.5 Hz, 1H, H6); 3.78
(dd, J¼4.6, 8.4 Hz, 1H, H6*); 3.82 (dd, J¼4.7, 8.5 Hz, 1H, H6); 7.19–
(m, 5H, ArH). 13C (100 MHz, CDCl3):
d¼17.3 (t, TMP–CCH2CH2), 20.3
(q, TMP–CH3), 20.4 (q, TMP–CH3), 28.4 (q, C(CH3)3), 33.7 (q, TMP–
CH3), 33.8 (q, TMP–CH3), 40.6 (t, TMP–CCH2), 55.6 (t, NCH2CHCO),
57.1 (t, NCH2CH]), 58.9 (t, PhCH2), 59.5 (s, TMP–C(CH3)2), 60.5 (s,
TMP–C(CH3)2), 80.9 (s, C(CH3)3), 85.4 (d, CHOTMP), 117.8 (t,
CH]CH2), 127.0 (d, CHAr), 128.2 (d, CHAr), 129.4 (d, CHAr), 135.5 (d,
CH]CH2), 139.2 (s, CAr), 172.6 (s, C]O).
4.2.7. Methyl 1-benzyl-4-[(2,2,6,6-tetramethylpiperidin-1-yloxy)-
methyl]pyrrolidine-3-carboxylate (6d). Isolated after flash chro-
matography (hexanes/EtOAc 50:1 to 2:1) as a pale yellow oil. For
yields and diastereomeric ratios see Table 2. [Rf (hexanes/EtOAc
7.35 (m, 10H, ArH, ArH*). 13C NMR (151 MHz, CDCl3):
d¼17.3 (t,
5:1)¼0.23]. IR (film); v [cmꢁ1]: 2973 (m), 2932 (m), 2792 (w, br),1735
TMP–CCH2CH2), 20.1 (q, TMP–CH3), 20.2 (q, TMP–CH3), 23.2 (q,
CHCH3*), 23.4 (q, CHCH3), 28.31 (q, C(CH3)3), 28.33 (q, C(CH3)3*),
33.3 (q, TMP–CH3), 33.6 (q, TMP–CH3), 39.8 (t, TMP–CCH2), 39.9 (d,
C4*), 40.1 (d, C4), 45.3 (d, C3), 45.5 (d, C3*), 54.4 (t, C2*), 55.2 (t, C2),
56.3 (t, C5*), 56.7 (t, C5), 59.8 (s, TMP–C(CH3)2), 60.0 (s, TMP–
C(CH3)2), 65.3 (d, CHCH3*), 65.7 (d, CHCH3), 76.1 (t, C6*), 76.5 (t, C6),
78.6 (s, C(CH3)3*), 80.7 (s, C(CH3)3), 126.93 (d, CHAr*), 126.96 (d,
CHAr), 127.3 (d, CHAr*), 127.4 (d, CHAr), 128.38 (d, CHAr*), 128.41 (d,
CHAr), 145.7 (s, CAr*), 145.8 (s, CAr), 172.6 (s, C]O*), 172.7 (s, C]O).
Resonances marked with * belong to (1R,3R,4S)-6e.
~
(s), 1362 (m), 1139 (s), 702 (m). MS (ESI) m/z, (%): 389 (MþHþ, 100),
288 (5). HRMS m/z, (C23H37N2O3; MþHþ): calcd 389.2799; found
389.2798. C23H36N2O3 (388.54): calcd C 71.10, H 9.34, N 7.21; found C
71.54, H 9.21, N 6.92. 1H NMR (400 MHz, CDCl3):
d¼0.96–1.04 (m,
24H, TMP–CH3, TMP–CH3*); 1.18 (m, 4H, TMP–CH2, TMP–CH2*); 1.35
(m, 8H, TMP–CH2, TMP–CH2*); 2.31 (t, J¼8.7 Hz, 1H, H5); 2.45 (dd,
J¼9.7, 12.9 Hz, 1H, H5*); 2.61 (dd, J¼8.1, 9.4 Hz, 1H, H2); 2.69 (m, 5H,
H4, H2*, H3*, H4*, H5*); 2.95 (m, 2H, H2, H5); 3.06 (dt, J¼7.9, 9.9 Hz,
2H, H3, H2*); 3.48 (d, J¼13.0 Hz,1H, PhCH2*); 3.59 (s, 3H, OCH3); 3.60
(m, 8H, PhCH2, PhCH2*, H6, H6*, OCH3*); 3.73 (dd, J¼6.2, 8.7 Hz, 2H,
H6, H6*); 7.16–7.27 (m, 10H, ArH, ArH*). 13C NMR (100 MHz, CDCl3):
4.2.9.2. (1R,3S,4S)-6e. 1H NMR (600 MHz, CDCl3):
d¼1.07 (s, 3H,
d¼17.3 (TMP–CCH2CH2), 20.16 (q, TMP–CH3), 20.18 (q, TMP–CH3),
TMP–CH3); 1.09 (s, 3H, TMP–CH3); 1.15 (s, 3H, TMP–CH3); 1.16 (s,
3H, TMP–CH3); 1.30 (m, 1H, TMP–CH2); 1.34 (d, J¼6.7 Hz, 3H,
CHCH3); 1.39–1.45 (m, 4H, TMP–CH2); 1.41 (s, 9H, C(CH3)3); 1.53 (m,
1H, TMP–CH2); 2.58 (m, 1H, H4); 2.60 (m, 1H, H5); 2.71 (m, 1H, H2);
2.74 (m, 1H, H2); 2.75 (m, 1H, H5); 2.93 (dt, J¼10.0, 7.6 Hz, 1H, H3);
3.21 (q, J¼6.7 Hz, 1H, CHCH3); 3.78 (m, 2H, H6); 7.19–7.35 (m, 5H,
33.2 (q, TMP–CH3), 33.3 (q, TMP–CH3), 39.9 (t, TMP–CCH2), 40.3 (d,
C4), 41.5 (d, C4*), 44.4 (d, C3), 46.1 (d, C3*), 51.5 (q, OCH3*), 51.7 (q,
OCH3), 56.4 (t, C2), 56.86 (t, C2*), 56.91 (t, C5*), 57.9 (t, C5), 59.91 (s,
TMP–C(CH3)2), 59.92 (s, TMP–C(CH3)2), 60.0 (t, PhCH2*), 60.5 (t,
PhCH2), 76.2 (t, C6), 78.5 (t, C6*), 127.08 (d, CHAr*), 127.13 (d, CHAr),
128.37 (d, CHAr*), 128.43 (d, CHAr), 128.8 (d, CHAr*), 128.9 (d, CHAr),
139.3 (s, CAr*), 139.4 (s, CAr), 173.8 (s, C]O), 174.0 (s, C]O*). Reso-
nances marked with * belong to 3,4-trans-6d.
ArH). 13C NMR (151 MHz, CDCl3):
d
¼17.0 (t, TMP–CCH2CH2), 20.06
(q, TMP–CH3), 20.10 (q, TMP–CH3), 23.04 (q, CHCH3), 28.0 (q,
C(CH3)3), 33.02 (q, TMP–CH3), 33.06 (q, TMP–CH3), 39.5 (t, TMP–
CCH2), 41.2 (d, C4), 46.4 (d, C3), 55.41 (t, C2 or C5), 55.47 (t, C2 or
C5), 59.5 (s, TMP–C(CH3)2), 59.6 (s, TMP–C(CH3)2), 65.0 (d, CHCH3),
78.3 (t, C6), 80.2 (s, C(CH3)3), 126.8 (d, CHAr), 127.1 (d, CHAr), 128.2
(d, CHAr), 145.6 (s, CAr), 173.9 (s, C]O).
4.2.8. Methyl 3-(N-allyl-N-benzylamino)-2-(2,2,6,6-tetramethylpi-
peridin-1-yloxy)propanoate (5d). Colorless oil, for yields see Table 2.
[Rf (hexanes/EtOAc 10:1)¼0.63]. IR (film); v [cmꢁ1]: 3064 (w), 2975
~
(m), 2930 (w),1744 (s),1361 (m),1040 (s), 740 (s), 698 (s). MS (ESI) m/
z, (%): 411 (MþNaþ, 80), 389 (MþHþ,100),160 (80) [CH2]N(All)Bnþ].
HRMS m/z, (C22H36N2O3Na; MþNaþ): calcd 411.2618; found 411.2616.
4.2.10. (R,R- and R,S)-tert-Butyl 3-[N-allyl-N-(1-phenylethyl)amino]-
2-(2,2,6,6-tetramethylpiperidin-1-yloxy)propanoates (5e). Colorless
oil, for yields see Table 3. [Rf (hexanes/EtOAc 10:1)¼0.49]. IR
1H NMR (400 MHz, CDCl3):
d
¼0.94–1.09 (m,12H, TMP–CH3); 1.22 (m,
(film); v [cmꢁ1]: 3062 (w), 2975 (m), 2931 (m), 1734 (s), 1365 (s),
~
2H, TMP–CH2), 1.35 (m, 4H, TMP–CH2); 2.78 (dd, J¼5.4, 12.4 Hz, 1H,
NCHHCHCO); 2.87 (m, 2H, NCHHCHCO, NCHHCH]); 3.03 (dd, J¼5.8,
14.2 Hz, 1H, NCHHCH]); 3.39 (d, J¼13.5 Hz, 1H, PhCHHN); 3.62 (s,
3H, OCH3); 3.64 (d, J¼13.0 Hz, 1H, PhCHHN); 4.34 (dd, J¼5.4, 10.4 Hz,
1148 (s), 916 (m), 701 (s). MS (ESI) m/z, (%): 467 (MþNaþ, 100),
445 (MþHþ, 50), 174 (70) [CH2]NAll(PhCHCH3)þ]. HRMS m/z,
(C27H44N2O3Na; MþNaþ): calcd 467.3244; found 467.3243. 1H