M.Lautens et al.
MOM-benzyl ether 46: NaBH4 (662 mg, 17.5 mmol) was added in one
portion to aryl aldehyde 45 (4.00 g, 17.5 mmol) in MeOH (80 mL) at RT.
After stirring for 1 h, the reaction was carefully diluted with H2O
(100 mL) and EtOAc (200 mL).The layers were separated and the aque-
ous layer was extracted with EtOAc (2200 mL); the combined organic
layers were dried (MgSO4) and solvent evaporated under reduced pres-
sure to give the crude benzyl alcohol.Following the procedure to prepare
benzyl ether 26, the addition of LiBr (304 mg, 3.5 mmol) and p-
TsOH.H2O (333 mg, 1.75 mmol) to the crude benzyl alcohol in dime-
thoxymethane (40 mL) gave after work-up and column chromatography
(20% EtOAc in hexane) aryl bromide 46 (3.51 g, 73%) as a colorless oil
IR (CHCl3): n˜
=
3429br, 3018m, 1703s, 1505s, 1484s, 1455s, 1215s,
1040 cmꢀ1 s; MS (EI): m/z: 473 (3) [M+], 323 (22), 322 (100), 91 (55);
HRMS: m/z: calcd for C27H23NO7: 473.1475, found 473.1483 [M+].
1,2-Dihydronaphthalene 50: Following the procedure to prepare dihydro-
naphthalene 41, the addition of CBr4 (501 mg, 1.51 mmol) to a solution
of benzyl alcohol 49 (478 mg, 1.01 mmol) and PPh3 (396 mg, 1.51 mmol)
in CH2Cl2 (10 mL) gave after work-up the crude benzyl bromide.The ad-
dition of NaH (60% in mineral oil; 60 mg, 1.51 mmol) to the crude
benzyl bromide in DMF (17 mL) gave after work-up and column chro-
matography (20% EtOAc in hexane) dihydronaphthalene 50 (414 mg,
90%) as a white foam.Mp..87–90 8C; [a]2D5 =+31 (c = 1.5 in CHCl3);
Rf =0.20 (20% EtOAc in hexane); 1H NMR: d = 7.52–7.28 (m, 5H),
6.70 (d, J=8 Hz, 1H), 6.63–6.61 (m, 2H), 6.52 (s, 1H), 6.42 (d, J=3.5 Hz,
1H), 6.41 (s, 1H), 5.90 (d, J=1.5 Hz, 1H), 5.86 (s, 1H), 5.85 (d, J=
1.5 Hz, 2H), 5.76 (brs, 1H), 5.30 (s, 2H), 5.04 (brs, 1H), 4.43 (d, J=
which solidified on standing.Mp..42–44
8C (lit.[34] 43–458C); Rf =0.33
1
(25% EtOAc in hexane); H NMR: d = 7.05 (d, J=8.5 Hz, 1H), 6.65 (d,
J=8.5 Hz, 1H), 6.01 (s, 2H), 4.72 (s, 2H), 4.67 (s, 2H), 3.43 ppm (s, 3H);
13C NMR: d = 148.0, 146.9, 125.3, 119.0, 116.2, 109.4, 101.8, 96.1, 63.0,
55.5 ppm; IR (neat): n˜ = 2884m, 2822w, 1499m, 1458s, 1378m, 1259s,
1238s, 1149s, 1046 cmꢀ1 s; MS (EI): m/z: 276 (65) [M+], 274 (66) [M+],
213 (54), 215 (55), 135 (100); HRMS: m/z: calcd for C10H1179BrO4:
273.9841, found 273.9843 [M+].
13 Hz, 1H), 3.58 ppm (brs, 1H); 13C NMR: d
145.3, 142.8, 136.4, 128.5, 128.1, 128.0, 128.0, 127.9, 127.7, 127.5, 127.4,
119.2, 114.4, 107.6, 106.7, 105.6, 101.2, 100.9, 67.6, 53.1, 38.4, 34.7 ppm;
= 156.1, 147.3, 146.5,
IR (CHCl3): n˜
= 2896s, 1698s, 1600m, 1455m, 1312s, 1257s, 1105s,
1050 cmꢀ1 m; MS (ESI): m/z: 478 (90) [M+Na+], 395 (100), 305 (100),
304 (100); HRMS: m/z: calcd for C27H21NNaO6: 478.1261, found
478.1271 [M+Na+].
Boronic acid 47: Following the procedure to prepare boronic acid 25, the
addition of nBuLi (1.6m in hexanes; 7.50 mL, 12.0 mmol) to aryl bromide
46 (3.00 g, 10.9 mmol) in THF (50 mL) followed by BCAHTRE(UNG OiPr)3 (7.55 mL,
32.7 mmol), acidic work-up, column chromatography (50% EtOAc in
hexane) and recrystallization (H2O) gave boronic acid 47 (1.91 g, 73%)
Bromohydrin 51: Following the procedure to prepare bromohydrins 34
and 35, the addition of NBS (98 mg, 0.55 mmol) to a solution of dihydro-
naphthalene 50 (228 mg, 0.50 mmol) in THF (4.5 mL) and H2O (0.5 mL)
gave after work-up and column chromatography (20% EtOAc in
hexane) bromohydrin 51 (207 mg, 75%) as a pale brown solid.Mp..
as a white solid.Mp..148–150
8C; Rf =0.20 (50% EtOAc in hexane);
1H NMR: d = 7.44 (d, J=8.5 Hz, 1H), 6.82 (d, J=8.5 Hz, 1H), 6.27 (s,
2H), 5.99 (s, 2H), 4.77 (s, 2H), 4.71 (s, 2H), 3.41 ppm (s, 3H); 13C NMR:
d = 149.0, 146.7, 130.6, 127.1, 121.1, 108.2, 100.9, 95.1, 62.1, 55.9 ppm; IR
(CH2Cl2): n˜ = 3380br, 2949s, 1588m, 1451m, 1420m, 1355s, 1279 cmꢀ1 s;
MS (EI) m/z 240 (10) [M+], 239 (98), 179 (86), 178 (100), 148 (36), 135
(75), 76 (48); HRMS: m/z: calcd for C10H13BO6: 240.0800, found
240.0808 [M+].
1468C; [a]2D5 =+73 (c
= 2.8 in CHCl3); Rf =0.20 (40% EtOAc in
hexane); 1H NMR: d = 7.42–7.33 (m, 5H), 7.01 (d, J=8 Hz, 1H), 6.79
(s, 1H), 6.71 (d, J=8 Hz, 1H), 6.70 (s, 1H), 6.09 (d, J=6 Hz, 1H), 5.93
(s, 3H), 5.87 (s, 1H), 5.30 (d, J=12 Hz, 1H), 5.26 (d, J=12 Hz, 1H), 5.05
(d, J=17 Hz, 1H), 4.81 (d, J=8.5 Hz, 1H), 3.96 (d, J=17 Hz, 1H), 3.84
(brs, 1H), 1.73 (brs, 1H), 1.62 ppm (d, J=9.5 Hz, 1H); 13C NMR: d =
155.8, 148.9, 147.6, 145.8, 143.8, 136.3, 129.0, 128.5, 128.1, 127.8, 126.2,
125.4, 121.5, 115.5, 109.6, 107.1, 105.7, 101.6, 101.3, 72.5, 67.8, 53.4, 49.9,
39.9, 37.8 ppm; IR (CHCl3): n˜ = 3445br, 3013w, 2893w, 1699s, 1484m,
1261 cmꢀ1 m; MS (ESI): m/z: 574 (50) [M+Na+], 552 (5), 536 (60), 454
(65), 304 (30), 244 (100); HRMS: m/z: calcd for C27H2379BrNO7:
552.0655, found 552.0658 [M+H+].
1,2-Dihydronaphthalene 48: Following the procedure to prepare 1,2-dihy-
dronaphthalene 29 (except the reaction was stirred for 6 h), the addition
of the azabicycle 38 (1.39 g, 4.33 mmol) and boronic acid 47 (1.56 g,
6.50 mmol) in MeOH (12 mL) followed by Cs2CO3 (1.41 g, 4.33 mmol) to
[PdACHTREUNG(MeCN)2Cl2] (57 mg, 0.22 mmol) and (S)-tol-binap (161 mg,
0.24 mmol) in MeOH (12 mL) gave after column chromatography (15%
EtOAc in hexane) dihydronaphthalene 48 (1.90 g, 85%) as a colorless oil
(which solidified on drying under high vacuum), with an ee of 90% as de-
termined by chiral HPLC analysis (Chiralpak AD, hexane/2-propanol
85:15, flow rate 1 mLminꢀ1; tR = 22.6 (minor), 40.2 min (major)); recrys-
tallization (hexane) gave dihydronaphthalene 39 (1.68 g, 75%) as a white
solid with an ee of 99% as determined by chiral HPLC analysis.Mp. .55–
Epoxide 52: Following the procedure to prepare epoxide 36, the addition
of a solution of KOtBu (1m in THF; 0.36 mL, 0.36 mmol) to bromohy-
drin 51 (200 mg, 0.36 mmol) in THF (70 mL) gave after work-up epoxide
52 (162 mg, 95%) as a pale yellow solid.Mp..85 8C; [a]2D5 =+101 (c =
1.03 in CHCl3); Rf =0.30 (50% EtOAc in hexane); 1H NMR: d = 7.33–
7.29 (m, 5H), 7.08 (brs, 1H), 6.89 (s, 1H), 6.82 (d, J=8 Hz, 1H), 6.73 (d,
J=8 Hz, 1H), 5.96 (d, J=1.5 Hz, 1H), 5.93–5.91 (m, 3H), 5.76 (d, J=
8 Hz, 1H), 5.19 (app q, J=12 Hz, 2H), 4.99 (d, J=16 Hz, 1H), 4.32 (d,
578C; [a]2D6 =+6.1 (c
= 1.2 in CHCl3); Rf = 0.35 (50% EtOAc in
hexane); 1H NMR: d = 7.24–7.37 (m, 5H), 6.78 (s, 1H), 6.64–6.58 (m,
3H), 6.50 (dd, J=9.5, 2 Hz, 1H), 5.96–5.91 (m, 5H), 5.18–5.14 (m, 1H),
5.02–4.92 (m, 3H), 4.67–4.56 (m, 4H), 4.21 (brs, 1H), 3.36 ppm (s, 3H);
13C NMR: d = 155.6, 147.2, 147.1, 146.1, 136.4, 131.9, 129.6, 128.8, 128.5,
128.1, 127.8, 127.8, 127.8, 126.8, 122.2, 117.9, 108.2, 107.7, 107.0, 101.1,
101.1, 95.7, 66.6, 59.8, 55.5, 52.7, 40.0 ppm; IR (CHCl3): n˜ = 3393m,
2891s, 1714s, 1603w, 1505s, 1380s, 1233 cmꢀ1 s; MS (ESI): m/z: 540 (100)
[M+Na+], 413 (15), 395 (15), 305 (80), 275 (20); HRMS (ESI): m/z:
calcd for C29H27NNaO8: 540.1628, found 540.1615 [M+Na+].
J=16 Hz, 1H), 3.85–3.77 ppm (m, 3H); 13C NMR: d
= 152.0, 148.7,
147.0, 145.8, 143.1, 136.4, 128.6, 128.6, 128.4, 128.3, 128.1, 128.0, 127.6,
125.2, 121.5, 117.4, 110.0, 107.1, 101.2, 67.5, 58.2, 52.5, 51.4, 37.8,
37.0 ppm; IR (CHCl3): n˜ = 2897w, 1699s, 1557w, 1504m, 1464s, 1317m,
1250s, 1111m, 1040 cmꢀ1 s; MS (ESI): m/z: 472 (20) [M+H+], 428 (50),
411 (100), 321 (95), 320 (90), 293 (40); HRMS: m/z: calcd for C27H22NO7:
472.1390, found 472.1378 [M+H+].
Benzyl alcohol 49: Following the procedure to prepare benzyl alcohol 40,
the addition of conc.HCl (14 mL) to dihydronaphthalene 48 (1.00 g,
1.93 mmol) in iPrOH (50 mL) and THF (50 mL) gave after work-up and
column chromatography (20% EtOAc in hexane) benzyl alcohol 49
(667 mg, 75%) as a oil which solidified as a white foam on drying under
high vacuum.Mp..80–83 8C; [a]2D6 =ꢀ69 (c = 2.7 in CHCl3); Rf =0.40
(50% EtOAc in hexane); 1H NMR: d = 7.34–7.29 (m, 3H), 7.17–7.15
(m, 2H), 6.80 (s, 1H), 6.69 (d, J=8 Hz, 1H), 6.64–6.62 (m, 2H), 6.52 (dd,
J=10, 3 Hz, 1H), 6.03 (d, J=1 Hz, 1H), 5.97 (d, J=1 Hz, 1H), 5.95 (s,
2H), 5.90 (dd, J=10, 3 Hz, 1H), 5.18 (dd, J=10, 6.5 Hz, 1H), 4.94–4.91
(m, 2H), 4.83–4.78 (m, 2H), 4.72 (dd, J=12, 4 Hz, 1H), 4.30–4.27 (m,
1H), 3.02 ppm (dd, J=6, 4.5 Hz, 1H); 13C NMR: d = 155.7, 147.5, 147.2,
146.6, 146.3, 136.2, 131.6, 128.6, 128.4, 128.1, 128.0, 127.9, 127.8, 127.7,
126.6, 122.5, 121.2, 108.8, 107.8, 106.9, 101.1, 66.7, 56.2, 52.4, 40.8 ppm;
Diol 53: Following the procedure to prepare diol 44, the addition of
BiCl3 (3 mg, 8 mmol) to a solution of epoxide 52 (40 mg, 0.08 mmol) in
H2O (0.4 mL) and MeCN (0.4 mL) gave after work-up and column chro-
matography (50% EtOAc in hexane) diol 53 (36 mg, 86%) as a white
solid.Mp..120–122 8C; [a]2D5 =+93 (c = 1.0 in CHCl3); Rf =0.21 (70%
1
EtOAc in hexane); H NMR: d = 7.74 (d, J=8.5 Hz, 1H), 7.40–7.32 (m,
5H), 6.89 (s, 1H), 6.65 (d, J=8.5 Hz, 1H), 6.55 (s, 1H), 5.89–5.88 (m,
2H), 5.86 (d, J=16 Hz, 1H), 5.85 (d, J=16 Hz, 1H), 5.69 (brs, 1H), 5.26
(s, 2H), 4.95–4.93 (m, 1H), 4.52 (t, J=7.5 Hz, 1H), 4.06 (d, J=8 Hz,
1H), 3.87 (d, J=16 Hz, 1H), 3.74 (s, 1H), 3.15 (brs, 1H), 2.43 ppm (brs,
1H); 13C NMR: d = 155.5, 147.9, 147.6, 145.3, 142.9, 136.2, 130.9, 128.6,
128.6, 128.2, 128.0, 128.0, 126.5, 122.3, 115.5, 106.9, 105.7, 101.2, 101.1,
76.4, 70.6, 67.9, 53.3, 40.7, 37.7 pppm; IR (CHCl3): n˜ = 3419br, 2897w,
1684s, 1499m, 1481s, 1458m, 1321m, 1240m, 1042 cmꢀ1 s; MS (ESI): m/z:
2122
ꢀ 2008 Wiley-VCH Verlag GmbH & Co.KGaA, Weinheim
Chem. Eur. J. 2008, 14, 2112 – 2124