5366 J . Org. Chem., Vol. 63, No. 16, 1998
Brisander et al.
Exo-3: IR (film) 1963, 1984 cm-1. Anal. Calcd for C18H23
CrNO4: C, 58.5; H, 6.3; N, 3.8. Found: C, 58.2; H, 6.1; N,
3.8.
-
19.3, 11.7. Anal. Calcd for C19H26ClCrNO4: C, 54.3; H, 6.2;
N, 3.3. Found: C, 53.9; H, 6.4; N, 3.2.
Alkylation of endo-(3S)-5 (0.34 g, 0.92 mmol) with methyl
En d o- a n d exo-(3R)-[η6-3-(Dip r op yla m in o)ch r om a n ]Cr -
(CO)3 [en d o-(3R)-5 a n d exo-(3R)-5]. A mixture of (R)-1 (2.12
g, 0.009 mol) and Cr(CO)6 (3.99 g, 0.018 mol) in THF/Bu2O
(1:10) (50 mL) was heated at 120 °C under N2 for 48 h. The
reaction mixture was filtered through Celite, and the volatiles
were evaporated. The oily residue was chromatographed
[SiO2; EtOAc/n-hexane (1:9)] to give 1.37 g (41%) of endo-(3R)-5
and 1.42 g (42%) of exo-(3R)-5. A small sample of each isomer
was converted into the corresponding hydrochloride salts,
endo-(3R)-5‚HCl and exo-(3R)-5‚HCl, respectively.
endo-(3R)-5‚HCl: mp 138-139 °C; [R]D -26.8° (c 0.5,
MeOH).
iodide gave 0.27 g (77%) of en d o-(3S,4R)-[η6-4-m eth yl-3-
(d ip r op yla m in o)ch r om a n ]Cr (CO)3 [en d o-(3S,4R)-6].
A
small sample was converted into the corresponding hydrochlo-
ride salt, endo-(3S,4R)-6‚HCl.
endo-(3S,4R)-6‚HCl: mp 96-97 °C; [R]D +201° (c 1.0,
MeOH). Anal. Calcd for C19H26ClCrNO4: C, 54.3; H, 6.2; N,
3.3. Found: C, 54.6; H, 6.2; N, 3.4.
In the methylation reaction of exo-(3R)-5 (0.28 g, 0.76 mmol),
two products were formed, exo-(3R,4S)-[η6-4-m et h yl-3-
(d ip r op yla m in o)ch r om a n ]Cr (CO)3 [exo-(3R,4S)-6] (0.13 g,
45%) and exo-(3R,4R)-[η6-4-m et h yl-3-(d ip r op yla m in o)-
ch r om a n ]Cr (CO)3 [exo-(3R,4R)-7] (0.076 g, 26%). A small
sample of each isomer was converted into the corresponding
hydrochloride salt, exo-(3R,4S)-6‚HCl and exo-(3R,4R)-7‚HCl.
exo-(3R,4S)-6‚HCl: mp 142-144 °C; [R]D +239° (c 1.0,
endo-(3R)-5: 1H NMR (CDCl3, 270 MHz) δ 5.37-5.30 (m,
3H), 5.10-4.91 (m, 1H), 4.23 (ddd, J ) 10.5, 4, 2 Hz, 1H), 3.77
(dd, J ) 11, 10.5 Hz, 1H), 3.09 (dddd, J ) 11, 11, 6.5, 4 Hz,
1H), 2.76 (dd, J ) 16, 11 Hz, 1H), 2.65 (ddd, J ) 16, 6.5, 2 Hz,
1H), 2.47-2.42 (m, 4H), 1.48-1.36 (m, 4H), 0.92-0.82 (m, 6H);
13C NMR (CDCl3, 400 MHz) δ 233.7, 138.0, 94.7, 93.3, 92.0,
87.0, 83.7, 68.4, 52.7, 52.6, 26.7, 22.1, 11.7. Anal. Calcd for
MeOH); IR (NaCl, CHCl3) 1971, 1891 cm-1
.
exo-(3R,4S)-6: 1H NMR (CDCl3, 400 MHz) δ 5.61 (app d, 1H),
5.54 (app t, 1H), 4.95 (app d, 1H), 4.74 (app t, 1H), 4.22 (dd, J
) 11, 3 Hz, 1H), 3.88 (dd, J ) 11, 9.5 Hz, 1H), 2.83 (ddd, J )
10.5, 9.5, 3 Hz, 1H), 2.80 (dq, J ) 10.5, 6.5 Hz, 1H), 2.56-
2.38 (m, 4H), 1.56-1.34 (m, 4H), 1.43 (d, J ) 6.5 Hz, 3H), 0.87
(t, J ) 7.5 Hz, 6H); 13C NMR (CDCl3, 400 MHz) δ 234.1, 141.1,
101.3, 95.6, 95.2, 83.7, 77.5, 65.9, 58.0, 52.4, 32.0, 22.2, 18.9,
11.8. Anal. Calcd for C19H26ClCrNO4: C, 54.3; H, 6.2; N, 3.3.
Found: C, 54.5; H, 6.1; N, 3.1.
C
18H24ClCrNO4: C, 53.3; H, 6.0; N, 3.5. Found: C, 53.0; H,
5.7; N, 3.3.
exo-(3R)-5‚HCl: mp 145-147 °C; [R]D +19.6° (c 0.5, MeOH).
exo-(3R)-5: 1H NMR (CDCl3, 270 MHz) δ 5.41 (app d, 1H),
5.38 (app t, 1H), 5.13 (app d, 1H), 4.85 (app t, 1H), 4.19 (ddd,
J ) 10.5, 4, 2 Hz, 1H), 3.77 (dd, J ) 10.5, 10.5 Hz, 1H), 3.30
(dddd, J ) 11.5, 10.5, 6, 4 Hz, 1H), 2.71 (dd, J ) 17.5, 11.5
Hz, 1H), 2.61 (ddd, J ) 17.5, 6, 2 Hz, 1H), 2.56-2.34 (m, 4H)
1.55-1.38 (m, 4H), 0.85 (t, J ) 7 Hz, 6H); 13C NMR (CDCl3,
400 MHz) δ 233.9, 138.9, 95.8, 94.3, 94.0, 86.4, 80.6, 69.1, 52.7,
52.5, 27.7, 21.7, 11.8. Anal. Calcd for C18H24ClCrNO4: C, 53.3;
H, 6.0; N, 3.5. Found: C, 53.1; H, 5.7; N, 3.3.
exo-(3R,4R)-7‚HCl: mp 150-152 °C; [R]D +162° (c 0.8,
MeOH); IR (NaCl, CHCl3) 1964, 1888 cm-1
.
exo-(3R,4R)-7: 1H NMR (CDCl3, 400 MHz) δ 5.48 (app d, 1H),
5.46-5.41 (m, 1H), 5.16 (app d, 1H), 4.88 (app t, 1H), 4.23 (ddd,
J ) 10.5, 4, 1.5 Hz, 1H), 3.94 (dd, J ) 10.5, 10.5 Hz, 1H), 3.30
(ddd, J ) 10.5, 4, 4 Hz, 1H), 2.85 (ddq, J ) 7, 4, 1.5 Hz, 1H),
2.52 (t, J ) 7 Hz, 4H), 1.54-1.40 (m, 4H), 1.27 (d, J ) 7 Hz,
3H,), 0.89 (t, J ) 7 Hz, 6H); 13C NMR (CDCl3, 400 MHz) δ
233.7, 138.1, 99.5, 95.2, 94.2, 85.9, 80.1, 65.1, 55.4, 52.3, 32.8,
20.1, 18.1, 11.8. Anal. Calcd for C19H26ClCrNO4: C, 54.3; H,
6.2; N, 3.3. Found: C, 54.7; H, 6.1; N, 3.4.
En d o- a n d exo-(3S)-[η6-3-(Dip r op yla m in o)ch r om a n ]Cr -
(CO)3 [en d o-(3S)-5 a n d exo-(3S)-5]. endo-(3S)-5 and exo-
(3S)-5 were prepared from (S)-1 (0.68 g, 2.91 mmol), using the
same procedure as for the preparation of endo-(3R)-5 and exo-
(3R)-5, to give 0.44 g (41%) of endo-(3S)-5 and 0.51 g (47%)
exo-(3S)-5. A small sample of each isomer was converted into
the corresponding hydrochloride salts, endo-(3S)-5‚HCl and
exo-(3S)-5‚HCl, respectively.
endo-(3S)-5‚HCl: mp 124-125 °C; [R]D +24.3° (c 0.4,
MeOH). Anal. Calcd for C18H24ClCrNO4‚0.25H2O: C, 52.7;
H, 6.0; N, 3.4. Found: C, 52.7; H, 5.8; N, 3.4.
exo-(3S)-5‚HCl: mp 145-147 °C; [R]D -20.5° (c 0.5, MeOH).
Anal. Calcd for C18H24ClCrNO4: C, 53.3; H, 6.0; N, 3.5.
Found: C, 53.2; H, 5.8; N, 3.5.
Alkylation of exo-(3S)-5 (0.21 g, 0.57 mmol) with methyl
iodide gave 0.11 g (50%) of exo-(3S,4R)-[η6-4-m eth yl-3-
(d ip r op yla m in o)ch r om a n ]Cr (CO)3 [exo-(3S,4R)-6] and
0.058 g (27%) of exo-(3S,4S)-[η6-4-m eth yl-3-(d ip r op yla m i-
n o)ch r om a n ]Cr (CO)3 [exo-(3S,4S)-7]. A small sample of
each isomer was converted into the corresponding hydrochlo-
ride salts, exo-(3S,4R)-6‚HCl and exo-(3S,4S)-7‚HCl, respec-
tively.
exo-(3S,4R)-6‚HCl: mp 141-142 °C; [R]D +239° (c 1.0,
MeOH). Anal. Calcd for C19H26ClCrNO4: C, 54.3; H, 6.2; N,
3.3. Found: C, 54.1; H, 6.2; N, 3.3.
exo-(3S,4S)-7‚HCl: mp 148-149 °C; [R]D +163° (c 0.9,
MeOH). Anal. Calcd for C19H26ClCrNO4: C, 54.3; H, 6.2; N,
3.3. Found: C, 54.2; H, 6.2; N, 3.3.
Alk yla tion Rea ction s of en d o- a n d exo-[η6-3-(Dip r op y-
la m in o)ch r om a n ]Cr (CO)3 Com p lexes Usin g KN(SiMe3)2.
The following methylation reaction is representative: KN-
(SiMe3)2 (1.37 g, 6.87 mmol) was added to a stirred solution of
endo-(3R)-5 (0.25 g, 0.68 mmol) in THF (35 mL) under N2 at
room temperature. After 1 h, the reaction mixture was cooled
to 0 °C, and methyl iodide (0.96 g, 0.42 mL, 6.77 mmol) was
added droppwise. The stirring was continued for 15 min at
room temperature. The reaction was quenched with NH4Cl
(0.36 g, 6.73 mmol) and partitioned between H2O and ether.
The combined organic phases was dried (K2CO3), filtered, and
concentrated. The residue was chromatographed [SiO2; iso-
hexane followed by EtOAc/isohexane (1:10)] to give 0.21 g
(81%) of en d o-(3R,4S)-[η6-4-m et h yl-3-(d ip r op yla m in o)-
ch r om a n ]Cr (CO)3 [en d o-(3R,4S)-6]. A small sample was
converted into the corresponding hydrochloride salt, endo-
(3R,4S)-6‚HCl.
Alkylation of endo-5 (0.21 g, 0.57 mmol) with benzyl bromide
gave 0.15 g (57%) of en d o-tr a n s-[η6-4-ben zyl-3-(d ip r op y-
la m in o)ch r om a n ]Cr (CO)3 (en d o-10). A small sample was
converted into the corresponding hydrochloride salt, endo-10‚
HCl.
endo-10‚HCl: IR (NaCl, CHCl3) 1964, 1889 cm-1
.
endo-10: mp 100-102 °C; 1H NMR (CDCl3, 400 MHz) δ
7.35-7.13 (m, 5H), 5.37 (app d, 1H), 5.26 (app t, 1H), 5.01 (app
d, 1H), 4.86 (app t, 1H), 4.28 (dd, J ) 10.5, 4 Hz, 1H), 3.83
(dd, J ) 11, 10.5 Hz, 1H), 3.52 (dd, J ) 14, 2.5 Hz, 1H), 3.09
(ddd, J ) 10, 8.5, 2.5 Hz, 1H), 2.69 (dd, J ) 14, 8.5 Hz, 1H),
2.73 (ddd, J ) 11, 10, 4 Hz, 1H), 2.63-2.48 (m, 4H), 1.58-
1.36 (m, 4H), 0.93 (t, J ) 7.5 Hz, 6H); 13C NMR (CDCl3, 400
MHz) δ 233.7, 139.9, 137.6, 129.4 (2C), 128.9 (2C), 126.8, 98.4,
93.1, 92.1, 87.5, 85.9, 66.1, 58.6, 52.8, 40.4, 38.2, 22.7, 12.0.
Anal. Calcd for C25H30ClCrNO4‚0.5H2O: C, 59.5; H, 6.2; N,
2.8. Found: C, 59.4; H, 6.3; N, 3.1.
endo-(3R,4S)-6‚HCl: mp 98-99 °C; [R]D -199° (c 1.0,
MeOH); IR (NaCl, CHCl3) 1964, 1890, 1875 cm-1
.
endo-(3R,4S)-6: 1H NMR (CDCl3, 270 MHz) δ 5.46 (dd, J )
6.5, 1 Hz, 1H), 5.30 (dd, J ) 7.5, 1.5 Hz, 1H), 5.31 (ddd, J )
7.5, 6.5, 1 Hz, 1H), 5.04 (ddd, J ) 6.5, 6.5, 1.5 Hz, 1H), 4.24
(dd, J ) 10.5, 3.5 Hz, 1H), 3.77 (dd, J ) 10.5, 10.5 Hz, 1H),
2.73 (dq, J ) 10.5, 6.5 Hz, 1H), 2.60-2.39 (m, 1H), 2.46 (t, J
) 7.5 Hz, 4H), 1.31 (d, J ) 6.5 Hz, 3H), 1.54-1.27 (m, 4H),
0.87 (t, J ) 7 Hz, 6H); 13C NMR (CDCl3, 400 MHz) δ 233.7,
137.3, 98.9, 93.1, 92.6, 87.5, 84.9, 65.7, 59.8, 52.4, 32.2, 22.5,
Alkylation of endo-5 (0.21 g, 0.57 mmol) with allyl bromide
gave 0.17 g (73%) of en d o-tr a n s-4-a llyl-[η6-3-(d ip r op yla m i-
n o)ch r om a n ]Cr (CO)3 (en d o-11). A small sample was con-
verted into the corresponding hydrochloride salt, endo-11‚HCl.