A. Casaschi et al. / Tetrahedron 56 (2000) 7541–7551
7549
J2.0 Hz, 1H, CuCH), 4.12, 4.34 (2×d, J14.4 Hz, 2H,
CH2N), 4.64 (d, J13.5 Hz, 1H, CvCCH2O), 4.67 (d,
J2.0 Hz, 2H, CH2CuC), 4.73 (d, J13.5 Hz, 1H,
CvCCH2O), 4.91, 5.10 (2×s, 2H, CH2vC) and 7.00–
7.89 (m, 9H, ArH); m/z (%) 637 (Mϩ, 0.2), 495 (56), 284
(55), 170 (35), 144 (36), 143 (56), 142 (38), 141 (77), 98
(34), 97 (47), 77 (42), 69 (37), 67 (42), 56 (66), 55 (100), 43
(40), 41 (64) and 39 (57).
Macrolide 19d (n5). Colourless needles from n-hexane/
ether, mp 61–63ЊC. (Found: C, 64.7; H, 6.1; N, 2.85; S, 6.6.
C26H29NO6S requires: C, 64.6; H, 6.05; N, 2.9; S, 6.65%); d
1.34–1.43 (m, 2H, CH2), 1.73 (m, 4H, 2×CH2CH2CO),
2.36–2.46 (m, 6H, 2×CH2CO and CCH2CvC), 3.67 (d,
J11.0 Hz, 1H, CH2N), 3.70–3.96 (m, 3H, CCH2O and
1H of CH2N), 4.09 (s, 1H, CH2vC), 4.33, 4.48 (2×d,
J12.5 Hz, 2H, CvCCH2O), 4.76 (s, 1H, CH2vC) and
7.04–7.85 (m, 9H, ArH); m/z (%) 483 (Mϩ, 10), 271 (27),
270 (100), 168 (15), 167 (11), 141 (26), 130 (27), 129 (12),
77 (33), 55 (16) and 41 (10).
Diester 17g (n8). Colourless needles (52%) from
n-hexane/ether, mp 64–67ЊC. (Found: C, 53.6; H, 5.2; N,
2.3; S, 4.8. C29H34INO6S requires: C, 53.45; H, 5.25; N,
2.15; S, 4.9%); d 1.30 (m, 8H, 4×CH2), 1.56–1.78 (m,
4H, 2×CH2CH2CO), 2.27–2.37 (m, 4H, 2×CH2CO), 2.49
(t, J1.8 Hz, 1H, CuCH), 4.10, 4.33 (2×d, J14.4 Hz,
2H, CH2N), 4.64 (d, J13.5 Hz, 1H, CvCCH2O), 4.67
(d, J1.8 Hz, 2H, CH2CuC), 4.73 (d, J13.5 Hz, 1H,
CvCCH2O), 4.90, 5.09 (2×s, 2H, CH2vC) and 7.00–
7.88 (m, 9H, ArH); m/z (%) 651 (Mϩ, 0.5), 510 (97), 288
(64), 284 (89), 270 (33), 144 (56), 143 (100), 142 (55), 141
(37), 77 (61), 55 (55), 41 (31) and 39 (36).
Macrolide 19e (n6). Colourless needles from n-hexane/
ether, mp 31–34ЊC. (Found: C, 65.2; H, 6.3; N, 2.7; S, 6.5.
C27H31NO6S requires: C, 65.15; H, 6.25; N, 2.8; S, 6.45%);
d
1.26–1.43 (m, 4H, 2×CH2), 1.70–1.75 (m, 4H,
2×CH2CH2CO), 2.36–2.45 (m, 6H, 2×CH2CO and
CCH2CvC), 3.73 (d, J11.0 Hz, 1H, CH2N), 3.88 (br s,
2H, CCH2O), 3.97 (d, J11.0 Hz, CH2N), 4.11, 4.24 (2×d,
J10.0 Hz, 2H, CvCCH2O), 4.26 (s, 1H, CH2vC), 4.65
(d, J2.8 Hz, 1H, CH2vC) and 7.02–7.84 (m, 9H, ArH);
m/z (%) 497 (Mϩ, 27), 272 (33), 271 (65), 270 (100), 168
(40), 167 (25), 141 (62), 130 (81), 129 (25), 78 (28), 77 (74),
55 (39) and 41 (25).
General procedure for spiro-macrolides 19a–g
The diesters 17a–g (0.25 mmol) were hydrostannylated and
cyclised using the same procedure as that described for the
synthesis of 10 but with a catalyst system comprising
Pd2dba3 (5 mol%) and tri(2-furyl)phosphine (20 mol%).
Product yields are collected in Table 3.
Macrolide 19f (n7). Colourless sticky oil. (Found: C,
65.45; H, 6.35; N, 2.5; S, 6.3. C28H33NO6S requires: C,
65.75; H, 6.5; N, 2.75; S, 6.3%); d 1.27–1.45 (m, 6H,
3×CH2), 1.66–1.73 (m, 4H, 2×CH2CH2CO), 2.34–2.47
(m, 4H, 2×CH2CO), 2.47, 2.59 (2×d, J16.0 Hz, 2H,
CCH2CvC), 3.72 (d, J11.0 Hz, 1H, CH2N), 3.78–3.94
(m, 3H, CCH2O and 1H of CH2N), 4.02 (d, J12.0 Hz,
1H, CvCCH2O), 4.26 (s, 1H, CH2vC), 4.28 (d,
J12.0 Hz, 1H, CvCCH2O), 4.80 (s, 1H, CH2vC) and
7.02–7.85 (m, 9H, ArH); m/z (%) 511 (Mϩ, 7), 272 (17),
271 (33), 270 (100), 168 (19), 149 (21), 141 (29), 130 (35),
77 (43), 55 (29) and 41 (21).
Macrolide 19a (n2). Colourless needles from n-hexane/
ether, mp 46–49ЊC. (Found: C, 62.7; H, 5.1; N, 3.1; S, 7.0.
C23H23NO6S requires: C, 62.55; H, 5.25; N, 3.15; S, 7.25%);
d 2.3 (d, J15.3 Hz, 1H, CCH2CvC), 2.53–2.66 (m, 5H,
2×CH2CO and 1H of CCH2CvC), 3.60 (d, J10.7 Hz, 1H,
CCH2O), 3.80, 3.98 (2×d, J11.0 Hz, 2H, CH2N), 4.01 (d,
J10.7 Hz, 1H, CCH2O), 4.35, 4.85 (2×d, J12.0 Hz, 2H,
CvCCH2O), 4.93, 5.31 (2×s, 2H, CH2vC) and 7.00–7.83
(m, 9H, ArH); m/z (%) 441 (Mϩ, 8), 441 (26), 271 (29), 270
(100), 167 (28), 149 (46) and 77 (22).
Macrolide 19g (n8). Colourless sticky oil. (Found: C,
66.0; H, 6.6; N, 2.5; S, 6.0. C29H35NO6S requires: C,
66.25; H, 6.7; N, 2.65; S, 6.1%); d 1.26–1.36 (m, 8H,
4×CH2), 1.67 (m, 4H, 2×CH2CH2CO), 2.19–2.37 (m, 4H,
2×CH2CO), 2.42, 2.56 (2×d, J15.0 Hz, 2H, CCH2CvC),
3.72 (d, J11.0 Hz, 1H, CH2N), 3.76–3.94 (m, 3H, CCH2O
and 1H of CH2N), 4.02, 4.18 (2×d, J11.5 Hz, 2H,
CvCCH2O), 4.38, 4.81 (2×s, 2H, CH2vC) and 7.00–
7.83 (m, 9H, ArH); m/z (%) 525 (Mϩ, 24), 523 (17), 272
(36), 271 (61), 270 (100), 168 (26), 141 (40), 130 (50), 77
(47) and 55 (26).
Macrolide 19b (n3). Colourless needles from n-hexane/
ether, mp 48–50ЊC. (Found: C, 63.6; H, 5.9; N, 2.7; S, 6.8.
C24H25NO6S requires: C, 63.3; H, 5.55; N, 3.05; S, 7.05%);
d 1.65–1.78 (m, 2H, CH2CH2CO), 2.41–2.52 (m, 6H,
2×CH2CO and CCH2CvC), 3.64 (d, J11.0 Hz, 1H,
CCH2N), 3.80, 3.88 (2×d, J11.5 Hz, 2H, CCH2O), 3.92
(d, J11.0 Hz, 1H, CCH2N), 4.60 (br s, 3H, CvCCH2O and
1H of CvCH2), 5.13 (s, 1H, CH2vC) and 7.00–7.88 (m,
9H, ArH); m/z (%) 455 (Mϩ, 7), 270 (100), 169 (38), 141
(25), 130 (27), 77 (35), 41 (15) and 39 (30).
General procedure for alkynes 21a–d
Methacryloyl chloride (2.4 g, 23 mmol) was added to a
stirred solution of 2-iodoaniline (5 g, 23 mmol) and triethyl-
amine (2.3 g, 23 mmol) in dichloromethane (50 ml) cooled
at 0ЊC. After 10 min the cooling bath was removed, the
mixture was stirred for 3 h at room temperature, then diluted
with CH2Cl2 (50 ml) and washed with water. The aqueous
layer was extracted twice with CH2Cl2 and the combined
organic layers dried (MgSO4), filtered and the filtrate
concentrated in vacuo. The residue was crystallised from
benzene to afford 20 (74%) as colourless prisms, mp
49ЊC. Sodium hydride (0.351 g, 60% dispersion in mineral
Macrolide 19c (n4). Colourless needles from n-hexane/
ether, mp 134–138ЊC. (Found: C, 64.0; H, 6.0; N, 2.8; S,
6.8. C25H27NO6S requires: C, 63.95; H, 5.8; N, 3.0; S,
6.85%); d 1.71–1.81 (m, 4H, 2×CH2CH2CO), 2.31–2.57
(m, 6H, 2×CH2CO and CCH2CvC), 3.83–3.96 (m, 4H,
CCH2O and CH2N), 4.26 (d, J12.5 Hz, 1H, CvCCH2O),
4.32 (s, 1H, CH2vC), 4.69 (d, J12.5 Hz, 1H,
CvCCH2O), 4.85 (s, 1H, CH2vC) and 7.04–7.85 (m,
9H, ArH); m/z (%) 469 (Mϩ, 21), 272 (10), 271 (25), 270
(100), 141 (14), 130 (12) and 77 (13).