SPECIAL TOPIC
Ti(III)-Promoted Reductive Cyclization
3165
(1S,2S,3S,4R,5S)-2,3,4-Tris(benzyloxy)-5-(hydroxymethyl)cy-
clopentanol (13) and (1S,2S,3R,4R,5S)-3,4-Bis(benzyloxy)-5-
(hydroxymethyl)cyclopentane-1,2-diol (14); Typical Procedure
A dark green soln of Cp2TiCl was prepared by stirring Cp2TiCl2
(105 mg, 0.42 mmol) with Zn dust (85 mg, 1.30 mmol) in THF (2
mL) at r.t. for 2 h. To this soln was added dropwise a soln of 7 (60
mg, 0.14 mmol) in THF (3.5 mL) at r.t. and the mixture was stirred
for 5 h. The reaction was quenched by addition of 10% aq H2SO4 (5
mL), the mixture was vigorously stirred for 10 min, CH2Cl2 (15 mL)
was added, and the phases were separated. The aqueous phase was
extracted with CH2Cl2 (2 × 10 mL). The combined organic phases
were washed with aq sat. NaHCO3 (10 mL) and brine (10 mL), dried
(anhyd Na2SO4), filtered, and concentrated at reduced pressure. The
residue was purified by flash chromatography (hexane–EtOAc, 1:1)
to afford 13 (25 mg, 41%) and 14 (5 mg, 10%) as colorless oils.
Compounds 13 and 14 were characterized as their corresponding di-
and triacetates, respectively, after acetylation with Ac2O in pyri-
dine.
H1¢, H 1¢¢), 3.67 (d, J = 9.4 Hz, 1 H, H6), 3.49 (d, J = 9.4 Hz, 1 H,
H6¢), 3.12 (s, 1 H, OH), 2.37 (t, J = 5.5 Hz, 1 H, OH), 2.32 (dt,
J = 4.9, 8.5 Hz, 1 H, H1).
13C NMR (75 MHz, C6D6): d = 138.3 (0), 138.1 (0), 138.0 (0), 137.5
(0), 128.3–127.5 (20 C, +), 87.7 (C4), 86.8 (C3, +), 82.7 (C2, +),
80.6 (C5, 0), 73.8 (C6, –), 73.0 (CH2Ph, –), 72.6 (CH2Ph, –), 72.6
(CH2Ph, –), 72.2 (CH2Ph, –), 60.5 (C1¢, –), 49.8 (C1, +).
(1S,2S,3R,4S,5S)-2,3,4-Tris(benzyloxy)-1-(benzyloxymethyl)-5-
(hydroxymethyl)cyclopentanol (16)
[a]D22 +8.82 (c 0.6, CHCl3).
1H NMR (400 MHz, C6D6): d = 7.33–7.02 (m, 20 H), 4.69–4.50 (m,
6 H, 3 CH2Ph), 4. 36 (t, J = 6.1 Hz, 1 H, H3), 4.17 (dd, J = 5.8, 1.2
Hz, 1 H, H2), 4.13–4.09 (m, 2 H, CH2Ph), 3.95 (d, J = 6.3 Hz, 1 H,
H4), 3.84–3.67 (m, 2 H, H1¢, H1¢¢), 3.43 (d, J = 10.0 Hz, 1 H, H6),
3.32 (d, J = 10.0 Hz, 1 H, H 6¢), 2.78 (s, 1 H, OH), 2.62 (br s, 1 H,
OH), 2.39 (m, 1 H, H1).
13C NMR (75 MHz, C6D6): d = 139.4 (0), 139.2 (0), 138.7 (0), 137.8
(0), 128.7–127.5 (20 C, +), 88.3 (C4, +), 82.9 (C3, +), 82.5 (C2, +),
78.0 (C5, 0), 73.8 (C6, –), 73.2 (CH2Ph, –), 72.5 (CH2Ph, –), 72.2
(CH2Ph, –), 72.1 (CH2Ph, –), 60.6 (C1¢, –), 53.9 (C1, +).
(1S,2R,3S,4R,5R)-1-Acetoxy-5-(acetoxymethyl)-2,3,4-tris(ben-
zyloxy)cyclopentane (13-Ac2)
[a]D22 +12.4 (c 0.12, CHCl3).
1H NMR (300 MHz, CDCl3): d = 7.36–7.26 (m, 15 H), 4.99 (t,
J = 5.6 Hz, 1 H, H1), 4.92–4.45 (m, 6 H, 3 CH2Ph), 4.12 (dd,
J = 1.0, 4.6 Hz, 2 H, H6, H6¢), 4.11 (t, J = 5.9 Hz, 1 H, H3), 3.99 (t,
J = 5.6 Hz, 1 H, H 2), 3.67 (dd, J = 5.6, 7.1 Hz, 1 H, H4), 2.41 (m,
1 H, H5), 2.09 (s, 3 H, Ac), 1.98 (s, 3 H, Ac).
13C NMR (75 MHz, CDCl3): d = 170.0 (0), 169.9 (0), 138.9 (0),
138.8 (0), 138.7 (0), 129.3–127.5 (15 C, +), 87.2 (C3, +), 81.7 (C4,
+), 81.0 (C2, +), 72.5 (C3-CH2Ph, –), 72.4 (C2-CH2Ph, –), 72.1
(C4-CH2Ph, –), 72.0 (C1, +), 62.8 (C6, –), 46.9 (C5, +), 20.5
(CH3CO, +) 20.2 (CH3CO, +).
1,3,4,5-Tetra-O-benzyl-7-chloro-7-deoxy-a-L-gluco-hept-2-ulo-
pyranose (17)
1H NMR (400 MHz, CHCl3): d = 7.35–7.17 (m, 20 H), 4.95–4.58
(m, 8 H, 4 CH2Ph), 4.11 (dt, J = 3.2, 9.9 Hz, 1 H, H1), 4.07 (t,
J = 9.3 Hz, 1 H, H3), 3.79 (d, J = 3.3 Hz, 2 H, H1¢, H1¢¢), 3.67 (t,
J = 9.5 Hz, 1 H, H 2), 3.52 (d, J = 9.5 Hz, 1 H, H4), 3.49 (s, 1 H,
OH), 3.48 (d, J = 10.6 Hz, 1 H, H6), 3.40 (d, J = 10.4 Hz, 1 H, H6¢).
13C NMR (75 MHz, CDCl3): d = 138.4 (0), 138.0 (0), 137.9 (0),
137.8 (0), 128.4–127.7 (20 C, +), 97.9 (C5, 0), 83.2 (C3, +), 79.3
(C4, +), 78.7 (C2, +), 75.6 (C3-CH2Ph), 75.4 (C4-CH2Ph), 75.2
(C2-CH2Ph), 73.8 (C6-CH2Ph), 71.7 (C6, –), 70.9 (C1, +), 44.8
(C1¢, –).
(1S,2R,3S,4R,5R)-1,2-Diacetoxy-5-(acetoxymethyl)-3,4-bis(ben-
zyloxy)cyclopentane (14-Ac3)
[a]D22 –0.75 (c 0.8, CHCl3).
MS (ESI+): m/z = 611.2 [M + Na]+, 606.2 [M + NH4]+.
1H NMR (300 MHz, CDCl3): d = 7.45–7.17 (m, 10 H), 5.21 (t,
J = 5.0 Hz, 1 H, H2), 5.07 (dd, J = 5.2, 8.7 Hz, 1 H, H 1), 4.73–4.49
(m, 4 H, 2 CH2Ph), 4.16 (d, J = 4.4 Hz, 2 H, H6, H6¢), 3.99 (t,
J = 4.1 Hz, 1 H, H3), 3.74 (dd, J = 4.4, 8.1 Hz, 1 H, H4), 2.48 (dt,
J = 4.4, 8.3, 12.6 Hz, 1 H, H5), 2.08 (s, 3 H, Ac), 2.04 (s, 3 H, Ac),
2.00 (s, 3 H, Ac).
13C NMR (75 MHz, CDCl3): d = 170.7 (0), 169.9 (2 C, 0), 137.8 (0),
137.6 (0), 129.4–127.7 (10C, +), 85.9 (C3, +), 81.3 (C4, +), 74.1
(C2, +), 72.3 (2 C, 2 CH2Ph), 70.6 (C1, +), 61.6 (C6, –), 45.8 (C5,
+), 20.7 (2 C, 2CH3CO, +), 20.6 (CH3CO, +).
1,3,4,5-Tetra-O-benzyl-7-deoxy-b-D-ido-hept-2-ulopyranose
(18)
1H NMR (500 MHz, CHCl3): d = 7.45–7.11 (m, 20 H), 4.73–4.24
(m, 8 H, 4 CH2Ph), 4.33 (d, J = 3.1 Hz, 1 H, H4), 4.07 (m, 1 H, H1),
3.99 (dd, J = 1.6, 10.2 Hz, 1 H, H6), 3.89 (dd, J = 1.8, 3.1 Hz, 1 H,
H3), 3.61 (dd, J = 1.8, 7.5 Hz, 1 H, H2), 3.09 (d, J = 10.2 Hz, 1 H,
H6¢), 3.00 (d, J = 1.6 Hz, 1 H, OH), 1.23 (d, J = 6.4 Hz, 3 H, CH3).
13C NMR (75 MHz, CDCl3): d = 139.0 (0), 137.8 (0), 137.8 (0),
137.7 (0), 128.7–127.1 (20 C, +), 95.1 (C5, 0), 79.7 (CH2Ph, –),
79.6 (C2, +), 73.9 (CH2Ph, –), 73.2 (CH2Ph, –), 72.7 (C3, +), 72.1
(C4, +), 72.0 (CH2Ph, –), 70.7 (C6, –), 66.5 (C1, +), 20.6 (CH3, +).
Reductive Cyclization of 4-Oxiranylaldehyde 8
Following the typical procedure from 7, compound 8 (100 mg, 0.23
mmol) was cyclized with Cp2TiCl to afford 13 (48 mg, 40%) and 14
(14 mg, 13%).
MS (ESI+): m/z = 577.1 [M + Na]+, 555.2 [M + 1]+.
Acknowledgment
Reductive Cyclization of 4-Oxiranyl Ketones 12a,b
Following the typical procedure from 7, the mixture of diastereo-
isomeric 4-oxiranyl ketones 12a,b (100 mg, 0.18 mmol) was cy-
clized to yield 15 (30 mg, 30%), 16 (15 mg, 15%), 17 (8 mg, 8%),
and 18 (12 mg, 12%), as colorless oils after column chromatogra-
phy (hexane–EtOAc, 2:1).
We thank MEC for financial support (projects BQU2003-03550-
C03-02 and CTQ2006-15515-C02-02/BQU) and Comunidad de
Madrid (predoctoral fellowship to E.S.).
References
(1R,2S,3R,4S,5S)-2,3,4-Tris(benzyloxy)-1-(benzyloxymethyl)-5-
(hydroxymethyl)cyclopentanol (15)
(1) For recent reviews on epoxide opening by single electron
transfer, see: (a) Gansauer, A.; Justicia, J.; Fan, C. A.;
Worgull, D.; Piestert, F. Top. Curr. Chem. 2007, 279, 25.
(b) Daasbjert, K.; Svith, H.; Grimme, S.; Gerenkam, M.;
Muck-Lichtenfeld, C.; Gansauer, A.; Barchuk, A. Top. Curr.
Chem. 2006, 263, 39.
[a]D22 –5.83 (c 0.7, CHCl3).
1H NMR (400 MHz, C6D6): d = 7.34–7.05 (m, 20 H), 4.68–4.51 (m,
8 H, 4 CH2Ph), 4.27 (dd, J = 5.8, 8.5 Hz, 1 H, H2), 4.06 (t, J = 5.5
Hz, 1 H, H3), 3.93 (d, J = 5.2 Hz, 1 H, H4), 3.85 (t, J = 5.3 Hz, 2 H,
Synthesis 2008, No. 19, 3160–3166 © Thieme Stuttgart · New York