Intermolecular and intramolecular ketone-nitrile reductive coupling reactions promoted by TiCl4-Sm system

Article abstract of DOI:10.1016/S0040-4020(00)00077-6

The intermolecular and intramolecular reductive coupling reactions of ketones with nitriles have been successfully promoted by low-valent titanium prepared by the TiCL₄-Sm system. Substituted ketones, monocyclic α-amino alcohols and monocyclic amines composed of a number of substitution patterns have been prepared in good yields at room or THF reflux temperature under neutral conditions. The procedure can avoid over reduction of the resulting of ketones, α-amino alcohols or amines. The crystal structures of two monocyclic α-amino alcohols are reported. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00077-6

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 2953±2960
Intermolecular and Intramolecular Ketone±Nitrile Reductive
Coupling Reactions Promoted by TiCl4±Sm System
Longhu Zhoua,b and Yongmin Zhanga,
*
aDepartment of Chemistry, Zhejiang University (Campus Xisi), Hangzhou 310028, People's Republic of China
bDepartment of Chemistry, Xuzhou Normal University, Xuzhou 221009, People's Republic of China
Received 13 September 1999; revised 4 January 2000; accepted 20 January 2000
AbstractÐThe intermolecular and intramolecular reductive coupling reactions of ketones with nitriles have been successfully promoted by
low-valent titanium prepared by the TiCl4±Sm system. Substituted ketones, monocyclic a-amino alcohols and monocyclic amines composed
of a number of substitution patterns have been prepared in good yields at room or THF re¯ux temperature under neutral conditions.
The procedure can avoid over reduction of the resulting of ketones, a-amino alcohols or amines. The crystal structures of two monocyclic
a-amino alcohols are reported. q 2000 Elsevier Science Ltd. All rights reserved.
Introduction
Results and Discussion
Carbon±carbon bond formation is the essence of organic
synthesis and the reductive coupling of carbonyl derivatives
is one of the most valuable methods for making carbon±
carbon bonds. Low-valent titanium reagent has an exceed-
ingly high ability in promoting reductive coupling of
carbonyl compounds and is attracting increasing interest
in organic synthesis. A lot of other functional groups can
also be coupled by this reagent.1 Recently, we have reported
a reductive cleavage reaction of Se±Se and Te±Te
bonds using the TiCl4±Sm system.2 Here we wish to report
a reductive cross-coupling reaction of nitrile derivatives
with carbonyl compounds promoted by TiCl4±Sm in
anhydrous THF.
Intermolecular ketone±nitrile cross-reductive coupling
reactions
Treatment of 1 equiv. of ketones (or aldehydes) 1 and
1.2 equiv. of nitriles 2 with low-valent titanium which was
prepared from 2 equiv. of TiCl4 and 2 equiv. of Sm powder,
gave substituted ketones 3 (or ole®ns 4) (Scheme 1). Table 1
summarizes the results on the intermolecular ketone±nitrile
It has been shown that the cyano group is relatively more
stable to low-valent titanium reagent than the carbonyl
group and it could only be reduced under re¯ux for a long
time in low yield.3 We considered that the intermediate
derived from a more active functional group by its treatment
with low-valent titanium could perhaps attack a more stable
functional group, which otherwise would not react with low-
valent titanium. Therefore, we have studied the behavior of
the cyano group and the carbonyl group with low-valent
titanium prepared by TiCl4±Sm in THF at room or re¯ux
temperature.
Scheme 1.
Table 1. TiCl4±Sm induced cross-coupling of ketones with nitriles
Entry
R1
R2
t (h)
Product (%)a
a
b
c
d
e
f
g
h
i
Ph
Ph
Ph
4-ClC6H4
Ph
4-CH3C6H4
C6H5CH2
Ph
4-CH3OC6H4
Ph
Ph
Ph
Ph
10
8
3a (81)b
3b (82)b
3c (70)b
3d (66)b
3e (73)b
3f (70)b
3g (72)b
3h (78)b
3a (41)c
4a (63)c
4a (79)b
4-CH3C6H4
Ph
Ph
4-CH3OC6H4
4-CH3OC6H4
4-ClC6H4
Ph
H
10
12
12
12
10
10
18
10
10
j
k
H
a Isolated yield.
Keywords: reductive coupling; ketones; a-amino alcohols.
* Corresponding author. Tel.: 1571-8273597; fax: 1571-8807707;
e-mail: wbao@public1.hz.zj.cn
b Reaction is carried out under re¯ux.
c Reaction is carried out at room temperature.
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00077-6

2954
L. Zhou, Y. Zhang / Tetrahedron 56 (2000) 2953±2960
Scheme 2. 7a: RˆPh, yield 51%; 7b: Rˆ4-CH3C6H4, yield 42%.
Scheme 3.
reductive couplings. When benzophenone and nitriles were
heated under re¯ux with TiCl4±Sm in a nitrogen atmos-
phere, ketones 3 were obtained in good yields (entries
a±h); if carried out at room temperature, the reaction is
slow and gives lower yields (entry 9). On the other hand,
treatment of aromatic aldehydes and nitriles with TiCl4±Sm
at room or re¯ux temperature did not give ketones 3, only
ole®ns 4 were obtained in good yields (entries j±k). For
comparison when the same reaction was carried out using
SmI2 as the reductant at re¯ux temperature, the cross-
coupled product (a-hydroxy ketone) was obtained and
ketone 3 was not found.4
Intramolecular ketone±nitrile reductive coupling
reactions
On the other hand, the intramolecular ketone±nitrile reduc-
tive coupling is dissimilar to the intermolecular one.
Substrates 8, which possess a carbonyl group and two
cyano groups, can undergo intramolecular ketyl±nitrile
reductive coupling reaction smoothly even at room tempera-
ture under a nitrogen atmosphere. The reductive cyclization
products 2-amino-3-cyano-1,4-diaryl-2-cyclopenten-1-ols 9
were obtained along with their diastereoisomers 10 in addi-
tion to 1-amino-2-cyano-3,5-diaryl-1-cyclopentenes 11
(Scheme 3). The intramolecular ketyl±nitrile reductive
coupling reaction products are different from those obtained
The intramolecular pinacol coupling reaction of diketones
can be promoted satisfactorily by low-valent titanium to
afford three-membered ring compounds.1 Attempts to
induce the cross-coupling between nitriles and diketones
were unsuccessful. Ketones are far more reactive than
nitriles and intramolecular coupling could occur much
easier than the cross-coupling reaction. An exception is
the case of dibenzoylmethane. When dibenzoylmethane 5
and nitriles 6 were treated with TiCl4±Sm at re¯ux tempera-
ture, pyrroles 7 were formed in moderate yield (entries a
and b). The great steric strain for the pinacol coupling
of dibenzoylmethane is probably the reason why the
reaction is driven to take the cross-coupling way
(Scheme 2).
using one-electron reducing agents such as Cp2TiPh,5 Zn/
TMSCl,6 SmI2
and electroreductive method,8 which
4,7
produce a-hydroxyketones. When the same reaction is
carried out at 2208C, only cyclopentenes 9 and 10 were
formed and products 11 were not detected. However, if
the reaction was carried out at about 658C, cyclopentenes
11 were obtained in good yield along with a smaller amount
of cyclopentenes 10 and products 9 were not found.
Table 2 summarizes the results of the intramolecular cycli-
zation of g-ketonitriles. All substrates were cyclized in good
yields. The reaction is highly chemoselective: only cycliza-
tion products were obtained. The pinacol coupling products
Table 2. TiCl4±Sm induced intramolecular ketone±nitrile coupling reaction
Entry
Substr.
Ar1
Ar2
T (8C)
t (h)
Isolated yield (%)
9
10
11
1
2
3
4
5
6
7
8
8a
8a
8a
8b
8b
8c
8c
8d
8d
8e
8e
8f
Ph
Ph
Ph
Ph
Ph
rt
220
65
220
65
220
65
220
65
220
65
220
65
3
4
3.5
6
3
4
3
5
3
9a (20)
9a (30)
±
9b (34)
±
9c (29)
±
9d (30)
±
9e (26)
±
±
±
10a (32)
10a (43)
±
10b (45)
10b (5)
10c (51)
±
10d (43)
10d (8)
10e (40)
±
10f (71)
±
11a (17)
±
11a (77)
±
11b (74)
±
11c (74)
±
11d (72)
±
11e (81)
±
11f (77)
Ph
4-CH3C6H4
4-CH3C6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
3,4-OCH2OC6H3
3,4-OCH2OC6H3
2-ClC6H4
2-ClC6H4
4-CH3C6H4
4-CH3C6H4
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
9
10
11
12
13
6
3.5
8
8f
2.5

L. Zhou, Y. Zhang / Tetrahedron 56 (2000) 2953±2960
2955
Figure 1. ORTEP diagram of 9c.
Figure 2. ORTEP diagram of 10c.
Scheme 4.

2956
L. Zhou, Y. Zhang / Tetrahedron 56 (2000) 2953±2960
of ketones were not detected. The chloro and alkoxyl groups
of the substrates could not be reduced under the reaction
conditions. The structures and relative con®guration of the
products have been established using spectroscopic data as
well as X-ray analysis. The X-ray diffraction studies on a
single crystal of 9c and 10c indicate that the products 9 (1,4-
cis) and 10 (1,4-trans) were diastereoisomers (Figs. 1 and 2).
Tetrahydrofuran (THF) was distilled from sodium-benzo-
phenone immediately prior to use. All reactions were
performed under a nitrogen atmosphere, using syringes
and Schlenk-type techniques. Titanium tetrachloride,
metallic samarium, aldehydes, dibenzoylmethane, diaryl
ketones, nitriles were purchased from commercial sources
and used without puri®cation. g-Ketonitriles 810 were
prepared from the reaction of chalcones with malononitrile
using KF±Al2O3 as catalyst at room temperature.
Though the detailed mechanism of the above reductive
coupling reaction has not yet been clari®ed, the formation
of monocyclic a-amino alcohols and amines or ketones
may be explained by a possible mechanism presented in
Scheme 4.
General procedure for the preparation of ketones pro-
moted by low-valent titanium
Under an inert atmosphere of nitrogen, TiCl4 (0.22 mL,
2 mmol) was added dropwise using a syringe to stirred
suspension of powdered samarium (0.30 g, 2 mmol) in
freshly distilled dry THF (20 mL) at room temperature.
After the completion of addition, the mixture was re¯uxed
for 2 h. A suspension of the low-valent titanium reagent was
formed and cooled to room temperature; then a solution of
diarylketone 1 (1 mmol) and nitrile 2 (1 mmol) in THF
(3 mL) was added dropwise. The mixture was stirred at
re¯ux temperature for the time indicated in Table 1. Then,
dilute HCl (5%, 4 mL) solution was added and the mixture
then extracted with ether (3£3 mL). After usual work-up,
the crude product was then puri®ed by preparative thin layer
chromatography of silica gel with dichloromethane-
petroleum ether (30±608C) (2:3) as the eluent to afford the
product.
In the intramolecular ketone±nitrile coupling reaction
(Scheme 4), after the formation of ketyl anion (A), ring
closure occurs via radical addition with the nitrile group;
then the carbon±nitrogen double bond is transferred to form
a carbon±carbon double bond due to stabilization by the
cyano group. If the reaction is carried out at lower tempera-
ture (2208C), the intermediates can be protonated to
2-amino-3-cyano-1,4-diaryl-2-cyclopenten-1-ols 9 and 10.
At higher temperature (658C), however, the intermediates
can be further reduced by the low-valent titanium, thereby
forming 1-amino-2-cyano-3,5-diaryl-1-cyclopentenes 11. In
the intermolecular reaction (Scheme 4), however, the
carbon±nitrogen double bond (in intermediate B0) could
not proceed to form a carbon±carbon double bond due to
the absence of a cyano group, and ketones 3 are formed.9 On
the other hand, the ketyl radical (A0) derived from aromatic
aldehydes has less steric hindrance than that of benzo-
phenone and the pinacol coupling reaction could proceed
prior to the ketone±nitrile reaction, with further reduction to
ole®n 4.
2,2-Diphenylacetophenone 3a. Mp 134±1368C (lit.11 138±
138.58C); nmax(KBr)/cm21 3100, 3080, 3045, 2940, 1690,
1640, 1600, 1500, 1400, 1360, 1205, 1030, 1010, 995, 760,
755, 735, 690; dH (CDCl3) 6.00 (1H, s, CH), 7.13±8.10
(15H, m, ArH).
In conclusion, low-valent titanium, prepared by TiCl4±Sm
system, induced ketone±nitrile reductive coupling reactions
have been studied. Although the cross-coupling reaction of
an aldehyde with a nitrile did not occur, the reactions afford
a variety of substituted ketones or a-amino alcohols and
amines in good yields. Further studies of this low-valent
reagent on other chemical transformations are now in
progress.
2,2-Diphenyl-(40-chloro)acetophenone 3b. Mp 108±
1108C (lit.12 108±1098C); nmax (KBr)/cm21 3040, 2980,
1690, 1600, 1580, 1500, 1405, 1210, 1030, 1090, 1005,
995, 835, 810, 745, 695; dH (CCl4) 5.90 (1H, s, CH),
7.15±7.95 (14H, m, ArH).
2-Phenyl-2-(40-methylphenyl)acetophenone 3c. Mp 97±
988C (lit.13 97.5±98.58C); nmax (KBr)/cm21 3040, 2930,
1695, 1600, 1500, 1450, 1360, 1205, 1005, 790, 750, 735,
710; dH (CDCl3) 2.26 (3H, s, CH3), 6.00 (1H, s, CH), 7.10±
8.20 (14H, m, ArH).
Experimental
General details
2,2-Diphenyl-40-methylacetophenone 3d. Mp 99±101
(lit.13 100±1018C); nmax (KBr)/cm21 3040, 2940, 1690,
1615, 1505, 1460, 780, 740, 695; dH (CCl4) 2.33 (3H, s,
CH3), 5.97 (1H, s, CH), 7.05±7.60 (12H, m, ArH), 7.89
(2H, d, Jˆ7.2 Hz, ArH).
a,a,a-Triphenylacetone 3e. Mp 82±83 (lit.14 848C); nmax
(KBr)/cm21 3050, 1680, 1610, 1500, 1460, 1060, 735, 690;
dH (CCl4) 3.67 (2H, s, CH2), 5.10 (1H, s, CH), 6.95±7.40
(15H, m, ArH).
Melting points are uncorrected. IR spectra were measured
with Perkin±Elmer 683 or FTIR-810 spectrophotometer in
KBr or CCl4. 1H NMR spectra were obtained on Bruker AC
300, Bruker AC 80 or JEOL PMX-60 spectrometers for
samples dissolved in CDCl3 or CCl4 using TMS as internal
standard; J values are given in Hz. Elemental analyses were
performed on a Carlo Erba 1106 instrument. Mass spectra
were obtained on a HP 5989A mass spectrometer using
electron impact mode (70 eV). Thin layer chromatography
(TLC) was performed on 0.5 mm silica gel (GF254) pre-
coated microscope slides and visualised with UV light
(254 nm). Preparative TLC was carried out on 1.5 mm silica
gel (GF254) pre-coated plate glass (20£20 cm) and
visualised with UV light (254 nm).
2,2-Diphenyl-40-methoxyacetophenone 3f. Mp 128±129
(lit.15 128±1308C); nmax (KBr)/cm21 3045, 1685, 1605,
1515, 1360, 1275, 1165, 1010, 820, 740, 720, 690; dH
(CCl4) 3.65 (3H, s, OCH3), 5.90 (1H, s, CH), 6.87 (2H, d,

L. Zhou, Y. Zhang / Tetrahedron 56 (2000) 2953±2960
2957
Jˆ9.0 Hz, ArH), 7.20±7.40 (10H, m, ArH), 8.01 (2H, d,
Jˆ9.0 Hz, ArH).
THF (3 mL) at room temperature under a nitrogen
atmosphere. The reaction mixture was then stirred at
2208C according to the reaction time in Table 2 and
quenched with dilute hydrochloric acid (5% HCl, 2 mL).
The mixture was extracted with diethyl ether (3£30 mL)
and the combined extracts were washed with saturated
aqueous NaCl (15 mL), and dried over anhydrous Na2SO4.
After evaporating the solvent under reduced pressure,
the crude product was puri®ed by preparative thin layer
chromatography on silica gel using ethyl acetate±cyclo-
hexane (1:2) as the eluent.
2-Phenyl-2-(40-methoxyphenyl)-40-methoxyacetophenone
3g. Low mp solid; nmax (KBr)/cm21 3050, 3015, 2950, 2950,
2860, 1690, 1610, 1510, 1470, 1260, 1215, 1170, 1030, 830,
780, 695, dH (CCl4) 3.58 (6H, s, 2£OCH3), 5.87 (1H, s, CH),
6.80 (4H, d, Jˆ9.0, ArH), 7.20±7.40 (10H, m, ArH), 8.01
(2H, d, Jˆ9.0, ArH); m/z 332 (M1, 2%), 197 (31), 165
(5), 153 (9), 135 (100), 107 (4), 92 (5), 77 (10). Anal.
for C22H20O3: Calcd (Found) C, 79.50 (79.81), H, 6.06
(6.18)%.
cis-2-Amino-3-cyano-1,4-diphenyl-2-cyclopentene-1-ol
(9a). 9a (83 mg) was obtained from ketonitrile 8a (275 mg)
as a white solid in 30% yield. Mp 168±1708C, nmax (KBr)/
cm21 3440, 3320, 2200, 1670, 1610, 1500. dH (CDCl3) 2.10
(1H, dd, Jˆ13.2, 7.5 Hz, H-5), 2.18 (1H, br s, OH), 2.80
(1H, dd, Jˆ13.2, 7.1 Hz, H-5), 3.92 (1H, dd, Jˆ7.5, 7.1 Hz,
H-4), 4.65 (2H, br s, NH2), 7.23±7.42 (10H, m, ArH); m/z
276 (M1, 34%), 258 (M2H2O, 100), 257 (25), 171 (9), 155
(20), 154 (23), 105 (69), 77 (75). Anal. for C18H16N2O:
Calcd (Found) C, 78.24 (78.50); H, 5.83 (5.60); N, 10.14
(9.97)%.
2-Phenyl-2-(40-chlorophenyl)acetophenone 3h. Mp 105±
1068C; nmax (KBr)/cm21 1690, 1640, 1605, 1590, 1500,
1455, 1220, 1090, 1020, 790, 740, 710, 690; dH (CDCl3)
6.15 (1H, s, CH), 7.30±7.70 (12H, m, ArH), 7.98±8.20 (2H,
m, ArH); m/z 306 (M1, 1%), 201 (9), 166 (10), 165 (18), 105
(100), 77 (20); Anal. for C20H15ClO: Calcd (Found) C, 78.30
(78.52); H, 4.92 (5.20)%.
General procedure for the low-valent titanium promoted
preparation of pyrroles 7
trans-2-Amino-3-cyano-1,4-diphenyl-2-cyclopenten-1-ol
(10a). 10a (119 mg) was obtained from ketonitrile 8a
(275 mg) as a white solid in 43% yield. Mp 164±1658C,
nmax (KBr)/cm21 3480, 3360, 2200, 1660, 1610, 1500. dH
(CDCl3) 2.18 (1H, dd, Jˆ14.2, 7.5 Hz, H-5), 2.25(1H, br s,
OH), 2.72 (1H, dd, Jˆ14.2, 7.3 Hz, H-5), 4.31 (1H, dd,
Jˆ7.5 Hz, H-4), 4.41(2H, br s, NH2) 7.26±7.50 (10H, m,
ArH); m/z 276 (M1, 59%), 258 (M2H2O, 100), 181 (24),
171 (10), 155 (22), 154 (23), 105 (66), 77 (67). Anal. for
C18H16N2O: Calcd (Found) C, 78.24 (78.47); H, 5.83 (5.57);
N, 10.14 (9.88)%.
To low-valent titanium (prepared from 2 mmol TiCl4 and
2 mmol powdered samarium) in dry THF (20 mL) was
added to a solution of dibenzoylmethane 5 (1 mmol) and
nitrile 6 (1.5 mmol) in anhydrous THF (3 mL) at room
temperature under a nitrogen atmosphere. The reaction
mixture was then stirred under re¯ux for about 2 days.
After the reaction was completed, as monitored by TLC,
the reaction was quenched with 10% K2CO3 (10 mL). The
mixture was extracted with dichloromethane (3£30 mL)
and the combined extracts were washed with saturated solu-
tion of NaCl (15 mL), and dried over anhydrous Na2SO4.
After evaporating the solvent under reduced pressure, the
crude product was puri®ed by preparative thin layer
chromatography on silica gel using diethyl ether±petroleum
(1:6) as the eluent.
cis-2-Amino-3-cyano-1-(p-methylphenyl)-4-(p-chloro-
phenyl)-2-cyclopenten-1-ol (9b). 9b (110 mg) was
obtained from ketonitrile 8b (320 mg) as a white solid in
34% yield. Mp 187±1898C. nmax (KBr)/cm21 3470, 3420,
3365, 2180, 1675, 1615, 1500. dH (CDCl3) 2.04 (1H, dd,
Jˆ13.0, 7.5 Hz, H-5), 2.37 (3H, s, CH3), 2.67 (1H, br s,
OH), 2.77 (1H, dd, Jˆ13.0, 7.1 Hz, H-5), 3.86 (1H, dd,
Jˆ7.5, 7.1 Hz, H-4), 4.58 (2H, br s, NH2), 7.14±7.40 (8H,
m, ArH); m/z 326 (M12, 7%), 324 (M1, 21), 308 (37), 306
(M2H2O, 100), 289 (28), 271 (26), 256 (14), 215 (16), 205
(5), 189 (6), 188 (4), 119 (64), 91 (55). Anal. for
C19H17ClN2O: Calcd (Found) C, 70.26 (70.50); H, 5.27
(5.47); N, 8.62 (8.36)%.
2,3,5-Triphenylpyrrole 7a. 7a (154 mg) was obtained from
dibenzoylmethane (230 mg) and benzonitrile (155 mg) in
51% yield. mp 139±1408C (lit.16 1428C). nmax (KBr)/cm21
3460, 1610, 1510, 1495, 1455, 1265, 1180, 1070, 955, 760,
690. dH (CDCl3) 6.50 (1H, s, CH), 7.05±7.75 (15H, m,
ArH), 8.20 (1H, s NH).
3,5-Diphenyl-2-(p-methylphenyl)pyrrole 7b. 7b (132 mg)
was obtained from dibenzoylmethane (230 mg) and
4-methylbenzonitrile (176 mg) in 42% yield mp 104±
1058C, nmax (KBr)/cm21 3420, 1600, 1480, 1450, 1260,
1070, 810, 790, 760, 700. dH (CDCl3) 2.30 (3H, s, CH3),
6.65 (1H, s, CH), 7.05±7.70 (14H, m, ArH), 8.30 (1H, s,
NH); m/z 309 (M1, 100%), 191 (11), 146 (7), 105 (8); Anal.
for C23H19N: Calcd (Found) C, 89.28 (88.95); H, 6.10
(6.10); N, 4.53 (4.62)%.
trans-2-Amino-3-cyano-1-(p-methylphenyl)-4-(p-chloro-
phenyl)-2-cyclopenten-1-ol (10b). 10b (145 mg) was
obtained from ketonitrile 8b (320 mg) as a white solid in
45% yield. Mp 170±1728C. nmax (KBr)/cm21 3490, 3390,
3250, 2190, 1660, 1605, 1500. dH (CDCl3) 2.08 (1H, dd,
Jˆ14.2, 7.4 Hz, H-5), 2.34 (3H, s, CH3), 2.66 (1H, dd,
Jˆ14.2, 7.3 Hz, H-5), 2.75 (1H, br s, OH), 4.21 (1H, dd,
Jˆ7.4, 7.3 Hz, H-4), 4.51 (2H, br s, NH2), 7.11±7.38 (8H,
m, ArH); m/z 326 (M12, 17%), 324 (M1, 49), 308 (35), 306
(M2H2O, 99), 289 (80), 271 (55), 256 (24) 215 (10), 205
(7), 189 (8), 188 (6), 119 (100), 91 (74). Anal. for
C19H17ClN2O: Calcd (Found) C, 70.26 (70.04); H, 5.27
(5.13); N, 8.62 (8.81)%.
General procedure for the low-valent titanium promoted
preparation of a-amino alcohols 9 and 10
To low-valent titanium (prepared from 2 mmol TiCl4 and
2 mmol powdered samarium) in dry THF (20 mL) was
added a solution of ketonitrile 8 (1 mmol) in anhydrous

2958
L. Zhou, Y. Zhang / Tetrahedron 56 (2000) 2953±2960
cis-2-Amino-3-cyano-1-phenyl-4-(p-chlorophenyl)-2-
cyclopenten-1-ol (9c). 9c (90 mg) was obtained from keto
nitrile 8c (310 mg) as a white solid in 29% yield. Mp 178±
1808C. nmax (KBr)/cm21 3490, 3420, 3360, 2180, 1680,
1625, 1500. dH (CDCl3) 2.06 (1H, dd, Jˆ13.0, 7.5 Hz,
H-5), 2.15 (1H, br s, OH), 2.78 (1H, dd, Jˆ13.0, 7.0 Hz,
H-5), 3.88 (1H, dd, Jˆ7.5, 7.0, H-4), 4.70 (2H, br s, NH2),
7.25±7.50 (9H, m, ArH); m/z 312 (M12, 10%), 310 (M1,
29), 294 (36), 292 (M2H2O, 100), 275 (53), 257 (41), 215
(10), 205 (8), 189 (7), 105 (62), 77 (48). Anal. for
C18H15ClN2O: Calcd (Found) C, 69.57 (69.82); H, 4.87
(4.99); N, 9.01 (8.87)%.
cis-2-Amino-3-cyano-1-phenyl-4-(3,4-methylenedioxy-
phenyl)-2-cyclopenten-1-ol (9d). 9d (97 mg) was obtained
from ketonitrile 8d (320 mg) as a pale yellow crystal in 30%
yield. Mp 164±1668C. nmax (KBr)/cm21 3470, 3390, 3250,
2200, 1660, 1610, 1510, 1455. dH (CDCl3) 2.05 (1H, dd,
Jˆ13.0, 7.5 Hz, H-5), 2.14(1H, br s, OH), 2.78 (1H, dd,
Jˆ13.0, 7.0 Hz, H-5), 3.85 (1H, dd, Jˆ7.5, 7.0 Hz, H-4),
4.68 (2H, br s, NH2), 5.94 (2H, s, OCH2O), 6.72±6.78 (3H,
m, ArH), 7.35±7.61 (5H, m, ArH); m/z 320 (M1, 100%),
302 (M2H2O, 47), 105 (33), 77 (23). Anal. for C19H16N2O3:
Calcd (Found) C, 71.24 (71.51); H, 5.04 (5.16), N, 8.74
(8.61)%.
Crystallographic data for 9c: C18H15ClN2O (310.78), color-
less, monoclinic; space group C2/c: aˆ24.416 (2),
trans-2-Amino-3-cyano-1-phenyl-4-(3,4-methylenedioxy-
phenyl)-2-cyclopenten-1-ol (10d). 10d (140 mg) was
obtained from ketonitrile 8d (320 mg) as a pale yellow
crystal in 43% yield. Mp 162±1648C, nmax (KBr)/cm21
3500, 3370, 3260, 2200, 1660, 1610, 1490, 1450. dH
(CDCl3) 2.06 (1H, br s, OH), 2.13 (1H, dd, Jˆ14.2,
7.5 Hz, H-5), 2.68 (1H, dd, Jˆ14.2, 7.3 Hz, H-5), 4.23
(1H, dd, Jˆ7.5, 7.3 Hz, H-4), 4.41 (2H, br s, NH2), 5.94
(2H, s, OCH2O), 6.75 (3H, s, ArH), 7.30±7.50 (5H, m,
ArH); m/z 320 (M1, 100%), 302 (M2H2O, 38), 105 (28),
77 (16). Anal. for C19H16N2O3: Calcd (Found) C, 71.24
(71.61); H, 5.04 (5.35); N, 8.74 (8.61)%.
Ê
bˆ12.215 (4), cˆ10.772 (4) A; bˆ97.78 (1)8; Vˆ3183
Ê 3
(1) A ; Zˆ8; Dcˆ1.297 g cm23; F(000)ˆ1296. Data were
collected with a Rigaku AFC7R diffractometer with v-scan
technique, graphite-monochromated Mo-Ka radiation
(lˆ0.71069 A, mˆ0.242 mm21) at 293 K. 3028 re¯ections
Ê
were measured, of which 2953 were independent re¯ections
with 2u in the range of 6 to 508, 1071 re¯ections having
I.2s (I). The structure was solved by direct methods17 and
expanded using Fourier techniques.18 All non-hydrogen
atoms were re®ned anisotropically. Hydrogen atoms were
included but not re®ned. The ®nal cycle of full-matrix
least-sequares re®nement give Rˆ0.058 and Rwˆ0.054
with wˆ1/s2(F0), Sˆ1.36. The maximum and the
minimum peak on the ®nal difference Fourier map
cis-2-Amino-3-cyano-1-phenyl-4-(o-chlorophenyl)-2-
cyclopenten-1-ol (9e). 9e (81 mg) was obtained from keto-
nitrile 8e (310 mg) as a white solid in 26% yield. Mp 171±
1728C. nmax (KBr)/cm21 3430, 3370, 3250, 2180, 1675,
1605, 1455, dH (CDCl3) 1.99 (1H, dd, Jˆ13.5, 6.4 Hz,
H-5), 2.08 (1H, br s, OH), 2.92 (1H, dd, Jˆ13.5, 7.6 Hz,
H-5), 4.43 (1H, dd, Jˆ7.6, 6.4, H-4), 4.66 (2H, br s, NH2),
7.19±7.49 (9H, m, ArH); m/z 312 (M12, 17%), 310 (M1,
48), 294 (28), 292 (M2H2O, 74), 275 (4), 257 (31), 215 (7),
205 (5), 189 (5), 105 (64), 77 (100). Anal. for C18H15ClN2O:
Calcd (Found) C, 69.57 (69.83); H, 4.87 (4.65); N, 9.01
(9.18)%.
Ê 3
corresponded to 0.26 and 20.26 e/A , respectively. All
calculations were performed using TEXSAN program
package.19
trans-2-Amino-3-cyano-1-phenyl-4-(p-chlorophenyl)-2-
cyclopenten-1-ol (10c). 10c (158 mg) was obtained from
ketonitrile 8c (310 mg) as a white solid in 51% yield. Mp
191±1938C. nmax (KBr)/cm21 3500, 3390, 2200, 1660,
1605, 1500. dH (CDCl3) 2.13 (1H, dd, Jˆ14.1, 7.5 Hz,
H-5), 2.21 (1H, br s, OH), 2.71 (1H, dd, Jˆ14.1, 7.3 Hz,
H-5), 4.28 (1H, dd, Jˆ7.5, 7.0 Hz, H-4), 4.36 (2H, br s,
NH2), 7.13±7.41 (9H, m, ArH); m/z 312 (M12, 14%),
324 (M1, 39), 294 (33), 292 (M2H2O, 95), 275 (100),
257 (48), 215 (6), 205 (7), 189 (7), 105 (85), 77 (58).
Anal. for C18H15ClN2O: Calcd (Found) C, 69.57 (69.75);
H, 4.87 (4.65); N, 9.01 (9.17)%.
trans-2-Amino-3-cyano-1-phenyl-4-(o-chlorophenyl)-2-
cyclopenten-1-ol (10e). 10e (124 mg) was obtained from
ketonitrile 8e (310 mg) as a white solid in 40% yield. Mp
183±1858C. nmax (KBr)/cm21 3460, 3370, 3250, 2190,
1660, 1460. dH (CDCl3) 2.05 (1H, dd, Jˆ14.3, 6.8 Hz,
H-5), 2.75 (1H, br s, OH), 2.86 (1H, dd, Jˆ14.3, 7.7 Hz,
H-5), 4.57 (2H, br s, NH2), 4.75 (1H, dd, Jˆ7.7, 6.8 Hz, H-4),
7.15±7.36 (9H, m, ArH); m/z 312 (M12, 21%), 310 (M1,
47), 294 (34), 292 (M2H2O, 89), 275 (5), 257 (12), 215 (5),
205 (4), 189 (3), 105 (68), 77 (100). Anal. for C18H15ClN2O:
Calcd (Found) C, 69.57 (69.79); N, 9.01 (9.25)%.
Crystallographic data for 10c: C18H15ClN2O (310.78), color-
less; orthorhombic; space group Pbcn: aˆ13.370 (5),
Ê
Ê 3
bˆ10.481 (5), cˆ23.350 (6) A; Vˆ3272 (3) A ; Zˆ8;
Dcˆ1.262 g cm23; F (000)ˆ1296. Data were collected
with a Rigaku AFC7R diffractometer with v-scan tech-
nique,
graphite-monochromated
Mo-Ka
radiation
trans-2-Amino-3-cyano-1-phenyl-4-(p-methylphenyl)-2-
cyclopenten-1-ol (10f). 10f (207 mg) was obtained from
ketonitrile 8g (290 mg) as a white solid in 71% yield. Mp
166±1688C. nmax (KBr)/cm21 3450, 3370, 3260, 2190,
1670, 1620, 1520. dH (CDCl3) 2.17 (1H, dd, Jˆ14.3,
7.4 Hz, H-5), 2.32 (3H, s, CH3), 2.67 (1H, dd, Jˆ14.3,
7.3 Hz, H-5), 2.85 (1H, br s, OH), 4.26 (1H, dd, Jˆ7.4,
7.3 Hz, H-4), 4.41 (2H, br s, NH2), 7.12±7.49 (9H, m,
ArH); m/z 290 (M1, 41%), 272 (M2H2O, 100), 257 (28),
198 (15), 181 (6), 163 (15), 155 (34), 154 (27), 119 (58), 91
(41). Anal. for C19H18N2O: Calcd (Found) C, 78.60 (78.31);
H, 6.25 (5.96); N, 9.65 (9.60)%.
(lˆ0.71069 A, mˆ0.236 mm21) at 293 K. 3278 re¯ections
were measured with 2u in the range of 6 to 508, 1551 re¯ec-
tions having I.2s (I). The structure was solved by direct
methods17 and expanded using Fourier tecnhiques.18 All
non-hydrogen atoms were re®ned anisotropically.
Hydrogen atoms were re®ned isotropically. The ®nal
cycle of full-matrix least-sequares re®nement give
Rˆ0.048 and Rwˆ0.051 with wˆ1/s2(F0), Sˆ1.54. The
maximum and the minimum peak on the ®nal difference
Ê
Ê 3
Fourier map corresponded to 0.20 and 20.22 e/A ,
respectively.

L. Zhou, Y. Zhang / Tetrahedron 56 (2000) 2953±2960
2959
General procedure for the low-valent titanium promoted
preparation of amines 11
nmax (KBr)/cm21; 3470, 3350, 3280, 3240, 2190, 1655,
1605, 1450, 1400, 1340, 1035, 745, 715, 695; dH (CDCl3)
1.60±2.32 (1H, m, H-4), 2.48±3.08 (1H, m, H-4), 3.87±4.00
(1H, m, H-3), 4.50 (2H, br s, NH2), 4.58±4.68 (1H, H-5),
7.15±7.50 (9H, m, ArH); m/z 296 (22%), 295 (45), 294
(M1,79), 293 (100), 292 (52), 259 (20), 258 (88), 183
(70), 155 (13), 91 (15), 77 (15); Anal. for C18H15N2Cl:
Calcd (Found) C, 73.34 (73.55); H, 5.13 (5.26); N, 9.50
(9.41)%.
To low-valent titanium (prepared from 2 mmol TiCl4 and
2 mmol samarium powder) in dry THF (20 mL) was added a
solution of ketonitrile 8 (1 mmol) in anhydrous THF (3 mL)
at room temperature under a nitrogen atmosphere. The
reaction mixture was then reacted at 608C according to the
reaction time in Table 2 and quenched with dilute hydro-
chloric acid (5% HCl, 2 mL). After usual work-up, the crude
product was puri®ed by preparative thin layer chromato-
graphy on silica gel using ethyl acetate±cyclohexane (1:3)
as the eluent.
1-Amino-2-cyano-3-( p-methylphenyl)-5-phenyl-1-cyclo-
pentene 11f. 11f (205 mg) was obtained from ketonitrile 8f
(280 mg) as colorless crystals in 77% yield, mp 190±1928C;
nmax (KBr)/cm21; 3500, 3360, 3280, 2195, 1665, 1610,
1460, 815, 760, 705; dH (CDCl3) 1.77±2.34 (1H, m, H-4),
2.35 (3H, s, CH3), 2.38±2.84 (1H, m, H-4), 3.87±4.18 (2H,
m, H-3, H-5), 4.38 (2H, br s NH2), 7.15±7.40 (9H, m, ArH);
m/z 274 (M1, 49%), 273 (M21, 59), 259 (100), 195 (13),
183 (52), 182 (27), 181 (43), 168 (23), 154 (21), 140 (19),
128 (26), 105 (20), 91 (42), 77 (42); Anal. for C19H18N2:
Calcd (Found) C, 83.18 (83.01); H, 6.61 (6.69); N, 10.21
(10.30)%.
1-Amino-2-cyano-3,5-diphenylcyclopentene 11a. 11a
(201 mg) was obtained from ketonitrile 8a (275 mg) as
colorless crystals in 77% yield, mp 185±1868C; nmax
(KBr)/cm21 3490, 3360, 3280, 2200, 1660, 1610, 1500,
1460, 1400, 1070, 750, 695; dH (CDCl3) 1.78±2.39 (1H,
m, H-4), 2.43±2.88 (1H, m, H-4), 3.88±4.24 (2H, m, H-3,
H-5), 4.41 (2H, br s, NH2), 7.19±7.41 (10H, m, ArH); m/z
261 (M11, 24%), 260 (M1, 83), 259 (M21, 100), 183 (36),
91 (9), 77 (12); Anal. for C18H16N2: Calcd (Found) C, 83.04
(83.25); H, 6.19 (6.24); N, 10.76 (10.45)%.
Acknowledgements
1-Amino-2-cyano-3-(p-chlorophenyl)-5-(p-methylphenyl)
cyclopentene 11b. 11b (230 mg) was obtained from keto-
nitrile 8b (320 mg) as colorless crystals in 74% yield, mp
145±1478C; nmax (KBr)/cm21; 3480, 3320, 2190, 1655,
1600, 1515, 1495, 1085, 810; dH (CDCl3) 1.69±2.30 (1H,
m, H-4), 2.36 (3H, s, CH3), 2.34±2.88 (1H, m, H-4), 3.84±
4.18 (2H, m, H-3, H-5), 4.43 (2H, br s, NH2), 7.06±7.74
(8H, m, ArH); m/z 310 (5.6%), 308 (M1, 32), 306 (46), 272
(100), 215 (10) 197 (26), 181 (18); Anal. for C19H17N2Cl:
Calcd (Found) C, 73.90 (74.06); H, 5.55 (5.78); N, 9.07
(9.23)%.
We are grateful to the National Natural Science Foundation
of China (Project No. 29672007 and 29872010), the NSF of
Zhejiang Province, China, and the Laboratory of Organo-
metallic Chemistry, Shanghai Institute of Organic
Chemistry, and the Chinese Academy of Science for
®nancial support.
References
1. (a) McMurry, J. E. Chem. Rev. 1983, 16, 405; (b) Lenoir, D.
Â
Synthesis 1989, 883; (c) FuÈrstner, A.; Bogdanovic, B. Angew.
Chem. Int. Ed. Engl. 1996, 35, 2442.
1-Amino-2-cyano-3-( p-chlorophenyl)-5-phenylcyclo-
pentene 11c. 11c (210 mg) was obtained from ketonitrile 8c
(209 mg) as colorless crystals in 74% yield, mp 157±1598C;
nmax (KBr)/cm21; 3490, 3360, 2220, 1660, 1615, 1500,
1460, 755, 695; dH (CDCl3) 1.73±2.25 (1H, m, H-4),
2.39±2.88 (1H, m, H-4), 3.88±4.20 (2H, m, H-3, H-5),
4.43 (2H, br s, NH2), 7.14±7.40 (9H, m, ArH); m/z 296
(12%), 294 (50), 293 (44), 292 (49), 259 (100) 183 (31);
Anal. for C18H15N2Cl: Calcd (Found) C, 73.34 (73.21); H,
5.13 (5.02); N, 9.50 (9.62)%.
2. (a) Zhou, L.; Zhang, Y. J. Chem. Res. (S) 1999, 27; (b) Zhou, L.;
Zhang, Y. Synth. Commun. 1999, 29 (3), 533.
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9031.
1-Amino-2-cyano-3-(3,4-methylenedioxyphenyl) cyclo-
pentene 11d. 11d (221 mg) was obtained from ketonitrile
8d (320 mg) as colorless crystals in 72% yield, mp 198±
2008C; nmax (KBr)/cm21; 3470, 3315, 2200, 1655, 1600,
1490, 1240, 1030, 920, 810, 775, 695; dH (CDCl3) 1.72±
2.32 (1H, m, H-4), 2.35±2.83 (1H, m, H-4), 3.86±4.15 (2H,
m, H-3, H-5), 1.41 (2H, br s, NH2), 5.93 (2H, s, OCH2O),
6.62±6.82 (3H, m, ArH), 7.16±7.40 (5H, m, ArH); m/z 304
(M1, 31%), 303 (100), 273 (25), 245 (13) 183 (34); Anal.
for C19H16N2O2: Calcd (Found) C, 74.98 (74.83); H, 5.30
(5.41); N, 9.20 (9.31)%.
8. Shono, T.; Kise, N.; Fujimoto, T.; Tominaga, N.; Morita, H.
J. Org. Chem., 1992, 57, 7175; (b) Shono, T.; Kise, N. Tetrahedron
Lett. 1990, 31, 1303.
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26.
10. Shi, D.; Lu, Z.; Wang, S.; Tu, S.; Dai, G. Synth. Commun.
1998, 28, 4003.
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14. Lagrave, R. Ann. Chim. 1927, 8, 408.
1-Amino-2-cyano-3-(o-chlorophenyl)-5-phenylcyclo-
pentene 11e. 11e (237 mg) was obtained from ketonitrile 8e
(311 mg) as colorless crystals in 81% yield, mp 169±1718C;
15. Nagano, J. J. Am. Chem. Soc. 1955, 77, 1691.

2960
L. Zhou, Y. Zhang / Tetrahedron 56 (2000) 2953±2960
16. Blatt, A. H. J. Am. Chem. Soc. 1934, 56, 2774.
17. Sheldrick, G. M. Crystallographic Computing 3; Oxford
University Press: London, 1985, p 175.
DIRDIF program: System Technical Report of the Crystallography
Laboratory, University of Nijmegen, The Netherlands, 1992.
19. TEXSAN: Crystal Structure Analysis Packages, Molecular
Structure Corporation (1985 and 1992).
18. Beurskens, P. T.; Admiraal, G.; Beurskens, G.; Bosman, W. P.;
Garcia-Granda, S.; Gould, R. O.; Smits, J. M. M.; Smykalla, C. The