Stereocontrolled Total Synthesis of (+)-1-Deoxynojirimycin
Ar-H), 7.61–7.52 (m, 1 H, Ar-H), 7.46–7.39 (m, 2 H, Ar-H), 6.45 (s, 1 H, 2-H), 5.42 (d, J = 17.2 Hz, 1 H, 2Ј-H), 5.31 (d, J = 10.4 Hz,
(br. s, 1 H, NH), 5.83 (ddd, J = 17.0, 10.6, 6.1 Hz, 1 H, 2-H), 5.58–
5.51 (dd, J = 6.0, 4.4 Hz, 1 H, 1-H), 5.46 (td, J = 17.0, 1.1 Hz, 1 NH), 4.03 (br. s, 1 H, 4-H), 3.72 (br. s, 1 H, 5-H), 3.61 (t, J =
H, 3-H), 5.40 (td, J = 10.6, 1.1 Hz, 1 H, 3-H), 4.48 (t, J = 8.9 Hz,
10.5 Hz, 1 H, 6b-H), 1.44 (s, 9 H, tBu) ppm. 13C NMR (100 MHz,
1 H, 5aЈ-H), 4.38 (dd, J = 8.9, 4.7 Hz, 1 H, 5bЈ-H), 4.16 (app. dt, CDCl3): δ = 155.0 (C=O), 137.6 (Cq-Ar), 134.5 (C-1Ј), 129.0 (C-
J = 8.9, 4.7 Hz, 1 H, 4Ј-H) ppm. 13C NMR (100 MHz, CDCl3): δ
Ar), 128.3 (C-Ar), 126.2 (C-Ar), 119.0 (C-2Ј), 101.0 (C-2), 82.1 (C-
1 H, 2Ј-H), 4.37 (dd, J = 10.5, 4.9 Hz, 1 H, 6a-H), 4.29 (br. s, 1 H,
= 165.5 (C=O), 159.7 (C=O), 133.5 (C-Ar), 130.7 (C-2), 129.8 (C- 4), 69.9 (C-6), 47.7 (C-5), 28.3 (C-tBu) ppm. MS (ESI): m/z = 306.0
Ar), 129.3 (C-Ar), 128.6 (Cq-Ar), 120.8 (C-3), 74.9 (C-1), 65.9 (C-
5Ј), 54.6 (C-4Ј) ppm. MS (ESI): m/z = 248.0 [M + H]+, 270.0 [M
+ Na]+.
[M + H]+, 328.0 [M + Na]+.
tert-Butyl [2-(Methoxymethoxy)allyl][(4S,5R)-2-phenyl-4-vinyl-1,3-
dioxan-5-yl]carbamate (8): To a stirred mixture of NaH (5.5 mg,
0.14 mmol, 60% in mineral oil) in dry DMF (0.20 mL) at 0 °C was
added dropwise a solution of benzylidene compound 7 (28.2 mg,
0.092 mmol) in dry DMF (1.5 mL). After being stirred for 45 min,
the mixture was treated dropwise with 3-iodo-2-(methoxymeth-
oxy)prop-1-ene (42.1 mg, 0.185 mmol) and then stirred for an ad-
ditional 1 h. Saturated aqueous NaHCO3 was added, and the mix-
ture was extracted with Et2O. The combined organic layers were
washed with brine, dried with MgSO4, filtered, and concentrated
under reduced pressure. Purification of the residue by flash
chromatography (SiO2/2.5% Et3N; pentane/Et2O, 9:1 to 7:3) af-
(R)-tert-Butyl 4-[(S)-1-(Benzoyloxy)allyl]-2-oxooxazolidine-3-carb-
oxylate (6Ј): A solution of oxazolidinone 6 (587 mg, 2.37 mmol),
Et3N (0.840 mL, 6.03 mmol), DMAP (94 mg, 0.77 mmol), and
Boc2O (1.86 g, 8.52 mmol) in CH2Cl2 (22 mL) was stirred for 1.5 h
and then concentrated under reduced pressure. Purification of the
residue by flash chromatography (SiO2/2.5% Et3N; pentane/Et2O,
7:3 to 4:6) gave Boc derivative 6Ј (753 mg, 91%) as white solid.
m.p. 72–73 °C. [α]2D0 = +101.9 (c = 1.0, CHCl ). IR (neat): ν
=
˜
3
max
2981, 2931, 1820, 1727, 1369, 1264, 1070 cm–1. 1H NMR
(400 MHz, CDCl3): δ = 8.04–7.98 (m, 2 H, Ar-H), 7.61–7.53 (m, 1
H, Ar-H), 7.49–7.39 (m, 2 H, Ar-H), 6.08 (ddd, J = 4.8, 3.4, 1.6 Hz,
1 H, 1Ј-H), 5.83 (ddd, J = 17.2, 10.8, 4.8 Hz, 1 H, 2Ј-H), 5.49–5.44
(m, 2 H, 3Ј-H), 4.44–4.36 (m, 2 H, 4,5a-H), 4.34 (t, J = 9.5 Hz, 1
H, 5b-H), 1.55 (s, 9 H, tBu) ppm. 13C NMR (100 MHz, CDCl3): δ
= 165.3 (C=O), 151.8 (C=O), 148.9 (C=O), 133.6 (C-Ar), 131.2 (C-
2Ј), 129.8 (C-Ar), 129.1 (Cq-Ar), 128.6 (C-Ar), 119.4 (C-3Ј), 84.6
(Cq-tBu), 72.4 (C-1Ј), 61.9 (C-5), 56.7 (C-4), 27.9 (C-tBu) ppm.
MS (ESI): m/z = 370.0 [M + Na]+. HRMS (FT, ESI): calcd. for
C18H21NO6 Na 370.12611, found 370.12701.
forded Boc derivative 8 (30.6 mg, 82%) as a colorless oil. [α]2D0
–43.4 (c = 1.0, CHCl ). IR (neat): ν = 2975, 1697, 1155,
=
˜
3
max
1
1023 cm–1. H NMR (400 MHz, CDCl3, mixture of rotamers): δ =
7.56–7.44 (m, 2 H, Ar-H), 7.41–7.28 (m, 3 H, Ar-H), 5.93 (ddd, J
= 17.3, 10.5, 6.8 Hz, 1 H, 1Ј-H), 5.64 and 5.55 (2 br. s, 1 H, 2-H),
5.42 and 5.37 (2 d, J = 17.6 Hz, 1 H, 2Ј-H), 5.28 and 5.26 (2 d, J
= 10.5 Hz, 1 H, 2Ј-H), 5.00–4.95 (m, 1 H), 5.01 and 4.96 (2 s, 2 H,
OCH2O), 4.47 (br. s, 1 H), 4.36 (m, 1 H), 4.29 (d, J = 12.6 Hz, 1
H), 4.16 (m, 2 H), 3.98 (s, 1 H), 3.61–3.41 (m, 1 H), 3.43 (s, 3 H,
CH3O), 1.54 and 1.45 (2 s, 9 H, tBu) ppm. 13C NMR (100 MHz,
CDCl3, mixture of rotamers): δ = 156.8, 156.6, 154.8, 138.0,
135.1,134.7, 128.9, 128.8, 128.2, 126.2, 126.1, 118.4, 118.2, 100.8,
93.9, 93.8, 93.7, 87.6, 86.5, 81.1, 80.2, 79.3, 78.5, 70.3, 68.3, 67.4,
56.3, 56.1, 28.6, 28.3 ppm. MS (ESI): m/z = 428.2 [M + Na]+.
HRMS (FT, ESI): calcd. for C22H31NO6Na 428.20436, found
428.20397.
tert-Butyl [(2R,3S)-1,3-Dihydroxypent-4-en-2-yl]carbamate (6ЈЈ):[15]
A solution of Boc derivative 6Ј (223 mg, 0.64 mmol) in dry ethanol
(14 mL) at 0 °C was treated dropwise with a solution of EtONa in
ethanol (0.80 mL, 2.4 , 1.9 mmol). The reaction mixture was
stirred at 0 °C for 1 h and then warmed to 20 °C over 1 h. Solid
NH4Cl was added, and the resulting mixture was filtered through
a plug of Celite. The filtrate was concentrated under reduced pres-
sure, and the residue was purified by flash chromatography (SiO2/
2.5% Et3N; pentane/AcOEt, 5:5 to 3:7) to give diol 6ЈЈ (130 mg,
93%) as a colorless oil. [α]2D0 = –4.2 (c = 0.7, CHCl3) {ref.[13] [α]2D3
(2R,4aR,7S,8R,8aR)-tert-Butyl 8-Hydroxy-7-(methoxymethoxy)-2-
phenyltetrahydro-4H-[1,3]dioxino[5,4-b]pyridine-5(4aH)-carboxylate
(9): A stirred solution of Boc derivative 8 (69.4 mg, 0.171 mmol),
Hoveyda–Grubbs 2nd-generation catalyst (10.7 mg, 0.017 mmol),
and benzoquinone (1.9 mg, 0.017 mmol) in degassed toluene
(2.0 mL) was refluxed for 4.5 h. The toluene was then removed un-
der reduced pressure, and the residue[16] was dissolved in THF and
treated dropwise at 0 °C with BH3·Me2S (0.071 mL, 0.748 mmol).
After being stirred at 20 °C for 7 h, the reaction mixture was treated
with water (2.0 mL), followed by NaBO3·4H2O (1.15 g,
7.48 mmol). After an additional 18 h at 20 °C, the mixture was ex-
tracted with AcOEt. The combined organic phases were washed
with brine, dried with MgSO4, filtered, and concentrated under re-
duced pressure. Purification of the residue by flash chromatography
= –5.4 (c = 1.1, CHCl )}. IR (neat): νmax = 3368, 2978, 2932, 1691,
˜
3
1510, 1170 cm–1. H NMR (300 MHz, CDCl3): δ = 5.94 (ddd, J =
1
17.2, 10.6, 5.3 Hz, 1 H, 4-H), 5.39 (td, J = 17.2, 1.5 Hz, 1 H, 5-H),
5.33 (br. s, 1 H, NH), 5.26 (td, J = 10.6, 1.5 Hz, 1 H, 5-H), 4.38
(m, 1 H, 3-H), 3.93 (dd, J = 11.2, 3.6 Hz, 1 H, 1a-H), 3.71 (dd, J
= 11.2, 3.6 Hz, 1 H, 1b-H), 3.63 (br. s, 1 H, 2-H), 2.91 (br. d, J =
3.0 Hz, 1 H, OH), 2.64 (br. s, 1 H, OH), 1.45 (s, 9 H, tBu) ppm.
13C NMR (100 MHz, CDCl3): δ = 156.4 (C=O), 137.4 (C-4), 116.5
(C-5), 79.9 (Cq-tBu), 74.9 (C-3), 62.5 (C-1), 54.9 (C-2), 28.4 (C-
tBu) ppm. MS (ESI): m/z = 239.9 [M + Na]+.
tert-Butyl [(2R,4S,5R)-2-Phenyl-4-vinyl-1,3-dioxan-5-yl]carbamate
(7):[15] A solution of diol 6ЈЈ (60 mg, 0.28 mmol), benzaldehyde di-
methyl acetal (0.084 mL, 0.560 mmol), and camphorsulfonic acid
(SiO2/2.5% Et3N; pentane/Et2O, 6:4 to 3:7) gave alcohol
(45.9 mg, 70%) as a white solid. M.p. 125–126 °C. [α]2D0 = +3.6 (c
= 1.0, CHCl ). IR (neat): νmax = 3449 (br.), 2972, 2924, 2890, 1697,
9
˜
3
(6 mg, 0.03 mmol) in CH2Cl2 (6 mL) was stirred at 20 °C for 6 h. 1146, 1090, 1020 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.54–7.46
Solid NaHCO3 was then added, the resulting mixture was filtered
through a plug of Celite, and the filtrate was concentrated under
reduced pressure. Purification of the residue by flash chromatog-
raphy (SiO2/2.5% Et3N; pentane/Et2O, 8:2 to 6:4) gave benzylidene
compound 7 (77 mg, 91%) as a white solid. m.p. 124–125 °C. [α]
(m, 2 H, Ar-H), 7.40–7.31 (m, 3 H, Ar-H), 5.57 (s, 1 H, 2-H), 4.76
(m, 3 H, 4-H and OCH2O), 4.37 (t, J = 10.0 Hz, 1 H, 4-H), 4.23
(dd, J = 13.6, 4.6 Hz, 1 H, 6-H), 3.74–3.58 (m, 2 H, 8,8a-H), 3.53
(ddd, J = 10.0, 7.7, 4.6 Hz, 1 H, 7-H), 3.43 (s, 3 H, CH3O), 3.24
(app. dt, J = 10.0, 4.6 Hz, 1 H, 4a-H), 2.80 (dd, J = 13.6, 10.0 Hz,
1 H, 6-H), 1.47 (s, 9 H, tBu) ppm. 13C NMR (100 MHz, CDCl3):
δ = 154.2 (C=O), 137.4 (Cq-Ar), 129.2 (C-Ar), 128.3 (C-Ar), 126.3
25 = –31.9 (c = 1.5, CHCl3) {ref.[13] [α]2D3 = –29.6 (c = 1.5, CHCl3)}.
D
IR (neat): ν
= 3349, 2981, 2855, 1680, 1528, 1307 cm–1. 1H
˜
max
NMR (400 MHz, CDCl3): δ = 7.58–7.45 (m, 2 H, Ar-H), 7.40–7.31 (C-Ar), 101.7 (C-2), 96.9 (OCH2O), 81.2 (Cq-tBu), 80.4 (C-8a),
(m, 3 H, Ar-H), 5.96 (ddd, J = 17.3, 10.5, 6.8 Hz, 1 H, 1Ј-H), 5.52 77.4 (C-7), 75.6 (C-8), 69.8 (C-4), 55.8 (OCH3), 54.4 (C-4a), 47.8
Eur. J. Org. Chem. 2009, 4221–4224
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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