3398
T. Oshitari, T. Mandai
LETTER
(13) For recent reviews, see: (a) Breit, B.; Seiche, W. Synthesis
2001, 1. (b) Breit, B. Acc. Chem. Res. 2003, 36, 264. For
syntheses of piperidines through Rh-catalyzed
7.3 Hz, 1 H), 7.15 (dt, J = 1.5, 8.2 Hz, 1 H), 7.20–7.31 (m,
5 H). 13C NMR (free base, CDCl3): d = 20.4, 28.2, 46.7, 47.8,
54.7, 54.8, 64.0, 109.8, 120.0, 126.3, 126.5, 127.8, 128.2,
129.6, 142.4, 157.6.
hydroformylation, see: (c) Ojima, I.; Tzamarioudaki, M.;
Eguchi, M. J. Org. Chem. 1995, 60, 7078. (d) Ojima, I.;
Iula, D. M.; Tzamarioudaki, M. Tetrahedron Lett. 1998, 39,
4599. (e) Ojima, I.; Vidal, E. S. J. Org. Chem. 1998, 63,
7999.
(20) Protection of C3-hydroxyl group as a benzoate was of choice
for the subsequent hydroformylation.
(21) Compound 13: colorless viscous oil; [a]D24 –152.3 (c = 1.02,
CHCl3). 1H NMR (CDCl3): d = 1.25 (br s, 6 H), 1.40–1.55
(br m, 3 H), 2.05–2.25 (m, 1 H), 2.40 (m, 1 H), 4.83 (br m,
0.33 H), 4.93 (br m, 0.67 H), 5.40 (br m, 0.33 H), 5.46–5.63
(m, 1.67 H), 7.00–7.35 (m, 6 H), 7.40 (m, 2 H), 7.55 (m, 1
H), 7.90 (m, 2 H). 13C NMR (CDCl3): d = 23.7, 24.0, 27.9,
28.2, 56.0, 57.3, 69.2, 81.3, 100.4, 126.1, 126.4, 127.5,
127.6, 128.0, 128.35, 128.38, 129.69, 129.71, 129.8, 133.1,
138.6, 152.3, 165.6. Anal. Calcd for C23H25NO4: C, 72.80;
H, 6.64; N, 3.69. Found: C, 72.76; H, 6.84; N, 3.66.
(22) Five-membered aminals (4%) were also isolated.
(23) Compound 14: colorless viscous oil; [a]D22 +56.7 (c = 1.3,
(14) {[3,3¢-di-tert-Butyl-2¢-(diphenoxymethoxy)-5,5¢-
dimethoxybiphenyl-2-yl]oxy}dibenzo[d,f][1,3]dioxepine.
(a) Billig, E.; Abatjoglou, A. G.; Bryant, D. R. U. S. Patent,
4668651, 1987. (b) Billig, E.; Abatjoglou, A. G.; Bryant, D.
R. U. S. Patent, 4769498, 1988. (c) Cuny, G. D.; Buchwald,
S. L. J. Am. Chem. Soc. 1993, 115, 2066.
(15) Five-membered N-Boc-enamide (2%) and five-membered
N-Boc-aminals (5%) were also isolated after the treatment
with CSA. N-Ts-enamide and N-Ts-aminals were not
obtained at all.
(16) Compound 10: colorless foam; [a]D22 –206.0 (c = 1.00,
CHCl3). 1H NMR (CDCl3): d = 1.21 (br s, 6.3 H), 1.41 (br s,
2.7 H), 1.77–1.85 (m, 1 H), 1.89–2.10 (br m, 1 H), 2.45 (s, 3
H), 3.87 (m, 1 H), 3.97 (d, J = 10.1 Hz, 1 H), 4.71 (br, 0.3
H), 4.78 (br, 0.7 H), 4.98 (br, 0.7 H), 5.15 (br, 0.3 H), 6.89–
7.22 (m, 2 H), 7.28–7.38 (m, 5 H), 7.78 (m, 2 H). 13C NMR
(CDCl3): d = 21.6, 25.5, 26.1, 27.9, 28.2, 49.8, 57.5, 58.9,
77.2, 81.3, 81.5, 101.0, 126.2, 126.6, 127.0, 128.0, 128.5,
129.9, 137.3, 137.7, 138.1, 143.7, 152.1. Anal. Calcd for
C23H28N2O4S: C, 64.46; H, 6.59; N, 6.54. Found: C, 64.37;
H, 6.71; N, 6.54.
(17) In the absence of TBAI, the N-alkylation was very slow at
0 °C. Compound 12, however, was afforded in 81% yield at
r.t. in 5 h with the significant loss of enantiomeric purity
(77% ee), which was probably caused by the elimination–
addition sequence of the N-2-methoxybenzyl-tert-butyl
carbamoyl group.
CHCl3) {Lit.1g [a]D15 +53.77 (c = 1.0, CHCl3); Lit.2d [a]D
25
+38.30 (c = 1.92, CHCl3)}. 1H NMR (CDCl3): d = 1.37 (s, 9
H), 1.54–1.62 (m, 1 H), 1.69 (m, 1 H), 1.76–1.87 (m, 3 H),
3.04 (m, 1 H), 4.01 (dd, J = 5.8, 12.8 Hz, 1 H), 4.09 (m, 1 H),
5.32 (d, J = 5.8 Hz, 1 H), 7.27 (m, 1 H), 7.37–7.32 (m, 2 H),
7.45 (m, 2 H). 13C NMR (CDCl3): d = 23.1, 27.7, 28.3, 39.5,
59.3, 70.1, 79.9, 127.2, 128.4, 138.5, 155.4. Anal. Calcd for
C16H23NO3: C, 69.29; H, 8.36; N, 5.05. Found: C, 69.21; H,
8.59; N, 4.77. The enantiomeric purity of 14 was determined
to be >99% ee by HPLC [CHIRALCEL OJ-H; hexane–i-
PrOH = 9:1; l = 220 nm; flow rate: 1.0 mL/min; tR(14) =
4.80 min; tR(ent-14) = 5.75 min].
(24) Compound 15: colorless oil; [a]D23 +43.3 (c = 1.60, CHCl3)
{Lit.1g [a]D28 +36.90 (c = 1.0, CHCl3)}. 1H NMR (CDCl3):
d = 1.46 (s, 9 H), 1.58–1.76 (m, 2 H), 1.94–2.05 (m, 2 H),
2.77 (ddd, J = 3.3, 13.4, 13.4 Hz, 1 H), 3.88 (m, 1 H), 3.95
(dd, J = 3.3, 13.4 Hz, 1 H), 4.71 (d, J = 12.5 Hz, 1 H), 4.75
(d, J = 12.5 Hz, 1 H), 5.70 (br s, 1 H), 7.25–7.36 (m, 3 H),
7.54 (br s, 1 H), 7.56 (br s, 1 H), 7.71 (br s, 2 H), 7.78 (br s,
1 H). 13C NMR (CDCl3): d = 24.2, 25.8, 28.4, 39.2, 55.4,
69.1, 78.7, 80.1, 121.4 (m), 123.3 (q, J = 272 Hz), 127.0,
127.2, 128.28, 128.32, 131.6 (q, J = 32.9 Hz), 138.0, 141.0,
155.3. The enantiomeric purity of 15 was determined to be
>99% ee by HPLC [CHIRALPAK IA; hexane–i-PrOH =
30:1; l = 220 nm; flow rate: 0.3 mL/min; tR(15)= 14.1 min;
tR(ent-15) = 16.6 min)].
(18) Compound 12: colorless foam; [a]D21 –105.2 (c = 1.32,
CHCl3). 1H NMR (CDCl3): d = 1.19–1.70 (m, 21 H), 1.85 (br
m, 1 H), 3.14 (br m, 1 H), 3.33 (br m, 1 H), 3.65 (s, 3 H), 3.75
(br m, 0.45 H), 3.99–4.10 (m, 1.65 H), 4.25 (br m, 0.45 H),
4.50 (br m, 0.45 H), 5.45 (br s, 0.9 H), 5.64 (br s, 0.1 H), 6.71
(m, 1 H), 6.86 (m, 1 H), 7.03 (m, 1 H), 7.12 (m, 1 H), 7.37–
7.25 (m, 5 H). 13C NMR (CDCl3): d = 22.4, 24.6, 28.2, 41.0,
41.6, 42.1, 55.1, 56.2, 57.0, 57.5, 77.2, 79.6, 109.8, 120.2,
126.4, 127.0, 128.0, 128.4, 140.2, 141.2, 155.9. Anal. Calcd
for C29H40N2O5: C, 70.13; H, 8.12; N, 5.64. Found: C, 69.90;
H, 8.28; N, 5.54. The enantiomeric purity of 12 was
determined to be >99% ee by HPLC [CHIRALCEL OD;
hexane–i-PrOH = 30:1; l = 220 nm; flow rate: 1.0 mL/min;
tR(12) = 6.8 min; tR(ent-12) = 11.0 min].
(25) L-733,060 (2): 1H NMR (free base, CDCl3): d = 1.53 (m, 1
H), 1.66–1.75 (m, 1 H), 1.88 (m, 1 H), 2.22 (br d, J = 14.0
Hz, 1 H), 2.85 (ddd, J = 3.1, 12.5, 12.5 Hz, 1 H), 3.29 (m, 1
H), 3.68 (br m, 1 H), 3.85 (d, J = 1.2 Hz, 1 H), 4.13 (d, J =
12.5 Hz, 1 H), 4.52 (d, J = 12.5 Hz, 1 H), 7.25–7.29 (m, 1 H),
7.30–7.35 (m, 2 H), 7.35–7.39 (m, 2 H), 7.44 (br s, 2 H), 7.69
(br s, 1 H). 13C NMR (free base, CDCl3): d = 20.5, 28.4, 47.1,
64.2, 70.0, 77.3, 121.1 (hept, J = 4.1 Hz), 123.2 (q, J = 271
Hz), 126.7, 127.0, 127.4 (m), 128.1, 131.2 (q, J = 32.9 Hz),
141.2, 141.9.
(19) (+)-CP-99,994 (1): 1H NMR (free base, CDCl3): d = 1.40 (br
d, J = 13.2 Hz, 1 H), 1.60 (m, 1 H), 1.76 (br s, 2 H), 1.93 (m,
1 H), 2.14 (br d, J = 13.1 Hz, 1 H), 2.76–2.83 (m, 2 H), 3.27
(m, 1 H), 3.41 (d, J = 13.8 Hz, 1 H), 3.44 (s, 3 H), 3.67 (d,
J = 13.8 Hz, 1 H), 3.88 (d, J = 2.1 Hz, 1 H), 6.68 (br d, J =
8.2 Hz, 1 H), 6.80 (br t, J = 7.3 Hz, 1 H), 6.97 (dd, J = 1.5,
Synlett 2006, No. 20, 3395–3398 © Thieme Stuttgart · New York