1266
G. Pandey, M. Kapur
PAPER
5-[(tert-Butyldimethylsilyl)oxy]-1,2-dideoxy-3,4-O-(1-methyl-
ethylidene)-D-threo-pent-1-yne (21)
1-[Benzyl(trimethylsilylmethyl)amino]-1,4,5-trideoxy-2,3-O-(1-
methylethylidene)-D-threo-pent-4-ynitol (17)
To a solution of 20 (600 mg, 1.39 mmol) in anhyd THF (4 mL) was
added a 2 M hexane solution of BuLi (3.5 mL, 7 mmol) at –78 °C
over a period of 5 min. The reaction mixture was stirred at –78 °C
for 1 h and was quickly brought up to 0 °C. Thereupon it was
quenched by rapid addition of a large excess of water (15 mL). The
mixture was extracted with EtOAc (3 10 mL) and the combined
organic extracts were dried (Na2SO4). The solvent was removed by
rotary evaporation and the residue was purified by column chroma-
tography (silica gel, hexane–EtOAc, 19:1) to afford 21 as a color-
A mixture of 23 (550 mg, 2.51 mmol), PhCH2NHCH2TMS (970
mg, 5 mmol), anhyd K2CO3 (1.73 g, 12.55 mmol) and TBAI (50 mg,
0.13 mmol) in anhyd MeCN (12 mL) was refluxed under argon for
about 96 h. The mixture was filtered and the filtrate concentrated.
The dark orange residue was column chromatographed (silica gel,
hexane–EtOAc, 19:1) to afford pure 17 as a colorless liquid (540
20
20
mg, 65%); [ ]D +1.2 (c = 21.2, CHCl3). L-isomer 26: [ ]D –0.7
(c = 11.0, CHCl3).
1H NMR (200 MHz, CDCl3): = 7.30 (m, 5 H), 4.39 (dd, J = 7.1, 2.0
Hz, 1 H), 4.25 (m, 1 H), 3.72 (d, J = 13.7 Hz, 1 H), 3.49 (d, J = 13.7
Hz, 1 H), 2.67 (dd, J = 13.1, 5.3 Hz, 1 H), 2.57 (dd, J = 13.1, 5.3 Hz,
1 H), 2.50 (d, J = 2.0 Hz, 1 H), 2.16 (d, J = 14.7 Hz, 1 H), 2.02 (d,
J = 14.7 Hz, 1 H), 1.47 (s, 3 H), 1.37 (s, 3 H), 0.05 (s, 9 H).
13C NMR (75 MHz, CDCl3): = 139.6, 128.8, 128.0, 126.7, 110.2,
81.6, 80.7, 74.1, 68.8, 62.8, 58.4, 47.2, 26.9, 25.9, –1.3.
20
less oil (340 mg, 90%); [ ]D +11.1 (c = 0.97, CHCl3). L-isomer:
[ ]D20 –10.7 (c = 1.18, CHCl3).
1H NMR (200 MHz, CDCl3): = 4.60 (dd, J = 7.4, 1.9 Hz, 1 H), 4.15
(m, 1 H), 3.80 (d, J = 4.4 Hz, 2 H), 2.55 (d, J = 1.9 Hz, 1 H), 1.45 (s,
3 H), 1.50 (s, 3 H), 0.90 (s, 9 H), 0.10 (s, 6 H).
13C NMR (75 MHz, CDCl3): = 110.4, 82.0, 81.1, 74.1, 66.8, 61.8,
26.7, 26.0, 25.6, 18.1, –5.6.
IR (neat): = 3300, 1460, 1380, 1260, 1220 cm–1.
MS: m/z (%) = 255 (M+ – 15, 8), 213 (2), 197 (3), 155 (100), 125
IR (neat): = 3310, 760, 720 cm–1.
MS: m/z (%) = 331 (M+, 8), 258 (10), 206 (100), 91 (80), 73 (19).
(66), 73 (44).
(3aR,7aR)-5-Benzyl-2,2-dimethyl-7-methylenehexa-
hydro[1,3]dioxolo[4,5-c]pyridine (16)
1,2-Dideoxy-3,4-O-(1-methylethylidene)-D-threo-pent-1-ynitol
(22)
A solution containing 17 (960 mg, 2.9 mmol) and 1,4-dicyanonaph-
thalene (160 mg, 0.9 mmol) in propan-2-ol (500 mL) was irradiated
in an open vessel using a 450 W Hanovia medium pressure mercury
vapor lamp as the light source. The lamp was immersed in a Pyrex
water-jacketed immersion well so as to allow only wavelengths
greater than 280 nm to pass through. After about 90 min of irradia-
tion, the consumption of the starting material was found to be al-
most complete and the irradiation was discontinued. The solvent
was removed under reduced pressure and the residue was column
chromatographed (silica gel, hexane–acetone, 20:1) to afford the
cyclized product 16 as a white crystalline solid (450 mg, 60%); mp
(uncorrected) 94–96° C; [ ]D20 –50.9 (c = 1.9, CHCl3). For the cor-
responding (3aS,7aS) isomer 27: [ ]D20 = +49.2 (c = 0.7, CHCl3).
1H NMR (200 MHz, CDCl3): = 7.30 (m, 5 H), 5.05 (d, J = 1.0 Hz,
1 H), 4.90 (d, J = 1.0 Hz, 1 H), 3.80 (m, 1 H), 3.73 (d, J = 13.2 Hz,
1 H), 3.65 (d, J = 13.2 Hz, 1 H), 3.57 (m, 1 H), 3.33 (m, 2 H), 2.80
(d, J = 12.7 Hz, 1 H), 2.37 (t, J = 10.3 Hz, 1 H), 1.45 (s, 6 H).
13C NMR (50 MHz, CDCl3): = 140.4, 137.7, 128.8, 128.2, 127.1,
110.9, 105.1, 81.7, 77.5, 61.5, 57.1, 54.5, 26.8, 26.6.
To a solution of 21 (700 mg, 2.59 mmol) in anhyd THF (3 mL), was
added a 1 M solution of TBAF in THF (3.10 mL) at 0 °C. The reac-
tion mixture was stirred at r.t. for about 4 h and to this was added
water (3 mL) followed by EtOAc (7 mL) and the layers were sepa-
rated. The organic layer was dried (Na2SO4) and concentrated under
reduced pressure. The crude mixture upon column chromatography
(silica gel, CHCl3–EtOAc, 9:1) afforded pure 22 as a colorless liq-
uid (345 mg, 85%); [ ]D20 +6.9 (c = 2.13, MeOH). L-isomer: [ ]D
–7.3 (c = 2.0, MeOH).
20
1H NMR (200 MHz, CDCl3): = 4.60 (dd, J = 7.9, 1.9 Hz, 1 H), 4.20
(m, 1 H), 3.94 (dd, J = 12.3, 3.0 Hz, 1 H), 3.68 (dd, J = 12.3, 3.2 Hz,
1 H), 2.55 (d, J = 1.9 Hz, 1 H), 1.80 (br s, 1 H), 1.50 (s, 3 H), 1.45
(s, 3 H).
13C NMR (50 MHz, CDCl3): = 110.6, 82.0, 80.7, 74.6, 66.2, 60.7,
26.6, 25.8.
IR (CHCl3): = 3446, 3290, 1460, 1379, 1215 cm–1.
MS: m/z (%) = 141 (M+ – 15, 64), 124 (11), 96 (47), 80 (31), 52
IR (CHCl3): = 1674, 769, 669 cm–1.
MS: m/z (%) = 259 (M+, 5), 201 (67), 91 (100).
(100).
(4S, 5R)-4-(Bromomethyl)-5-ethynyl-2,2-dimethyl-1,3-
dioxolane (23)
[(3aR,7R,7aR)-5-Benzyl-2,2-dimethylhexahydro[1,3]dioxolo-
[4,5-c]pyridin-7-yl]methanol (24)
To a stirred solution of CBr4 (1.50 g, 4.54 mmol) and 22 (590 mg,
3.78 mmol) in anhyd CH2Cl2 (12 mL) at 0 °C, was added Ph3P
(1.488 g, 5.67 mmol) in small portions. The resultant dark red solu-
tion was stirred at r.t. for 1 h. Large excess of hexane was added to
the mixture and the contents were quickly filtered through a pad of
silica gel. The solvent was removed in vacuo. The compound was
pure enough (660 mg, 80%, crude yield) and was used as such for
the next step. For spectral purposes, 23 was purified completely by
a quick flash column chromatography (silica gel, hexane–EtOAc,
94:6).
1H NMR (200 MHz, CDCl3): = 4.58 (dd, J = 6.4, 2.4 Hz, 1 H), 4.33
(m, 1 H), 3.50 (m, 2 H), 2.59 (d, J = 2.4 Hz, 1 H), 1.50 (s, 3 H), 1.45
(s, 3 H).
13C NMR (50 MHz, CDCl3): = 111.6, 80.7, 77.3, 75.0, 69.2, 31.1,
27.0, 26.3.
To a stirred solution of 16 (130 mg, 0.5 mmol) in THF (4 mL), was
added dropwise a 0.5 M THF solution of 9-BBN (10 mL, 5 mmol).
The resulting mixture was stirred at r.t. for about 20 h. To this was
added successively water (2 mL), 1 N NaOH solution (1.5 mL) and
30% solution of H2O2 (1.5 mL) at 0 °C. The mixture was stirred at
r.t. for 4 h and extracted with EtOAc (3 5 mL). The organic ex-
tracts were dried (Na2SO4) and concentrated in vacuo. The residue
upon chromatographic purification (silica gel, hexane–EtOAc, 3:2)
20
yielded 24 as a gummy mass (63 mg, 45%); [ ]D +14.8 (c = 0.5,
20
MeOH). For its enantiomer, the (3aS,7S,7aS) isomer: [ ]D –14.0
(c = 1.7, MeOH).
1H NMR (200 MHz, CDCl3): = 7.30 (m, 5 H), 3.70 (dd, J = 10.3,
3.9 Hz, 1 H), 3.65 (m, 4 H), 3.24 (dd, J = 9.3, 3.9 Hz, 1 H), 3.15 (dd,
J = 10.7, 8.9 Hz, 1 H), 2.95 (dd, J = 11.3, 3.9 Hz, 1 H), 2.18 (m, 2
H), 1.95 (m, 1 H), 1.45 (s, 6 H).
13C NMR (75 MHz, CDCl3): = 129.0, 128.2, 127.3, 110.9, 82.1,
77.3, 63.5, 61.9, 54.3, 53.4, 41.5, 26.7.
IR (neat): = 3310, 1400, 695 cm-1.
GC/MS: m/z = 205, 203 (both M+ – 15), 145, 143, 96.
Synthesis 2001, No. 8, 1263–1267 ISSN 0039-7881 © Thieme Stuttgart · New York