Synthetic Utility of Organometallic Reagents Derived from. Group IV Metal Tetrachlorides and CH3Li. A Direct Synthesis of 2-(2-Keto-1-alkylidene)tetrahydropyrroles from 4-Alkynylamines and Acyl Cyanides

Article abstract of DOI:10.1021/om9902380

The non-Cp-bearing titanium alkyls (CH₃)₂TiCl₂ · L₂(1a) and (CH₃)₂Ti(OTFE)Cl · L₂ (1b) and their Zr(IV) analogues have been shown to mediate efficient aminoalkyne cyclizations to provide azatitanium intermediates that undergo facial C-acylation in the presence of acyl cyanides.

Full text of DOI:10.1021/om9902380

Organometallics 1999, 18, 4421-4428
4421
Syn th etic Utility of Or ga n om eta llic Rea gen ts Der ived
fr om Gr ou p IV Meta l Tetr a ch lor id es a n d CH Li. A Dir ect
3
Syn th esis of 2-(2-Keto-1-a lk ylid en e)tetr a h yd r op yr r oles
fr om 4-Alk yn yla m in es a n d Acyl Cya n id es
David Duncan and Tom Livinghouse*
Department of Chemistry, Montana State University, Bozeman, Montana 59717
Received April 6, 1999
The non-Cp-bearing titanium alkyls (CH
3
)
2
TiCl
2
‚L
2
(1a ) and (CH
3
)
2
2
Ti(OTFE)Cl‚L (1b)
and their Zr(IV) analogues have been shown to mediate efficient aminoalkyne cyclizations
to provide azatitanium intermediates that undergo facial C-acylation in the presence of acyl
cyanides.
Group IV metallocene complexes have continued to
play a preeminent role as catalysts for alkene polym-
Resu lts a n d Discu ssion
1
The alkynylamines that were utilized in this study
were prepared by the general routes described previ-
ously. We commenced the present investigation by
exploring the ability of (CH3)2TiCl2‚L2 (1a ) to cyclize
representative alkynylamines (Scheme 1). In a typical
procedure, addition of 2 equiv of CH3Li to 2 in THF at
erization. Recently, interest has intensified in group
2
IV metal complexes containing amido as well as other
6
3
heteroatom (i.e., amidinato ) bearing ligands as polym-
erization catalysts. In addition, inexpensive non-Cp-
containing isopropoxytitanium complexes have been
found to mediate highly selective C-C bond formation
in a manner reminiscent of group IV metallocene
0
°C generated a light orange solution of the active
4
reagent 1a . Subsequent addition of the appropriate
alkynylamine 3 at 0 °C resulted in an immediate
evolution of CH4 with the homogeneous solution assum-
ing a rich burgundy color. After stirring at ambient
temperature for an additional 3 h, protonolysis of the
putative azatitanetine 4 (5% NaOH in MeOH) afforded
derivatives. Studies in these laboratories have revealed
that transient imido complexes generated by treatment
of CpTi(CH3)2Cl with alkynylamines undergo facile
intramolecular [2+2] cycloaddition to provide interme-
diates that subsequently engage in selective nucleophilic
coupling with acyl cyanides.5,6 In this article, we show
1
the corresponding ∆ -pyrrolines 5a -c in the indicated
that organotitanium derivatives of the type (CH3)2TiCl2‚
L2 (1a ), which can be directly prepared by treating
inexpensive TiCl4‚1,2-DME (2) with 2 equiv of CH3Li,
participate admirably in the aminoalkyne cyclization/
acyl cyanide coupling sequence. In addition, the corre-
sponding zirconium alkyls have been found to perform
in an analogous manner. Whereas (CH3)2TiCl2 is pre-
disposed toward disproportionation at ambient tempera-
yields after purification (Table 1). In the cases of 3b and
3
c, protodesilyation occurred upon quenching to provide
1
the corresponding ∆ -pyrrolines 5b and 5c. We have
previously shown that CpTiCl3 is a very effective
catalyst for the cyclization of 1-amino-4-alkynes to ∆ -
1
6
c
pyrrolines. It is therefore of interest that 2 is relatively
inactive as a catalyst for this interconversion.9
tures,7a the corresponding complexes with chelating
The reaction of the organometallic species derived
from 1a and 1-amino-4-alkynes with acyl cyanides was
subsequently examined. To this end, simple addition of
an acyl cyanide (1 equiv) to the preformed azatitanium
intermediate at 0 °C, followed by stirring at ambient
temperature for 72 h and final quenching (CH3OH),
furnished the anticipated 2-(2-keto-1-alkylidene)tetra-
hydropyrroles (6b-i) in good to excellent isolated yield
(Scheme 2). The results of a series of aminoalkyne
ethers (i.e., dioxane) have been described as compara-
tively stable.7b In light of these observations, TiCl4‚1,2-
DME (2) was selected as an appropriate Ti(IV) source
8
for initial examination.
(1) Mitchell, J . P.; Hajela, S.; Brookhart, S. K.; Hardcastle, K. I.;
Henling, L. M.; Bercaw, J . E. J . Am. Chem. Soc. 1996, 118, 1045-
1
053, and references therein.
2) (a) Scollard, J . D.; McConville, D. H. J . Am. Chem Soc. 1996,
18, 10008-10009. (b) Tinkler, S.; Deeth, R. J .; Duncalf, D. J .;
(
1
McCamley, A. J . Chem. Soc., Chem. Commun. 1996, 2623-2624.
3) Hagadorn, J . R.; Arnold, J . J . Chem. Soc., Dalton Trans. 1997,
087-3096, and references therein.
4) Okamoto, S.; Iwakubo, M.; Kobayashi, K.; Sato, F. J . Am. Chem.
Soc. 1997, 119, 6984-6990, and references therein.
5) For a comprehensive review in the area of aminoalkyne cycliza-
tions see: Muller, E. T.; Beler, M. Chem. Rev. 1998, 98, 676.
6) (a) Fairfax, D.; Stein, M.; Livinghouse, T.; J ensen, M. Organo-
4
(8) (a) Evaluation of TiCl ‚1,4-dioxane as a Ti(IV) source revealed
that this complex possessed no advantages relative to 2. (b) Ti(III)
complexes are not efficacious in the ac/acc sequence. Accordingly, the
use of TiCl ‚2THF in place of 2 led to aminoalkyne cyclization with
3
concomitant generation of an azatitanium intermediate that was
lethargic toward acyl cyanide interception.
(
3
(
(
(9) (a) Although 2 proved quite effective as a catalyst for the
cyclization of highly reactive aminoalkynes possessing a 5-trimethyl-
(
9
b
metallics 1997, 16, 1523-1525. (b) McGrane, P. L.; Livinghouse, T. J .
Am. Chem. Soc. 1993, 115, 11485-11489. (c) McGrane, P. L.; J ensen,
M. D.; Livinghouse, T. J . Am. Chem. Soc. 1992, 114, 5459-5460. (d)
McGrane, P. L.; Livinghouse, T. J . Org. Chem. 1992, 57, 1323-1324.
silyl substituent, comparatively less reactive substrates bearing
9c
5-alkyl or 5-aryl substituents cyclized inefficiently. (b) Li, Y.; Marks,
T. J . J . Am. Chem. Soc. 1996, 118, 9295-9306. (c) We wish to
acknowledge the early contribution of Dr. Phil Ho Lee, of these
laboratories, who first demonstrated the use of 1a for the cyclization
of 3b to 5b.
(7) (a) deButts, E. H. U.S. Patent 3,021,349, 1962. (b) Beerman, C.;
Beastian, H. Angew. Chem. 1959, 71, 618-623.
1
0.1021/om9902380 CCC: $18.00 © 1999 American Chemical Society
Publication on Web 09/17/1999

4
422 Organometallics, Vol. 18, No. 21, 1999
Duncan and Livinghouse
Sch em e 1
(entries 13 and 14).11 As had been previously observed,
protodesilyation could be effected by using a slightly
modified quenching procedure to afford the correspond-
ing heterocycles 7 in high yield (entries 2, 3, 5, 6, 8, 9).
After the foregoing studies, a variety of alternative,
non-Cp-bearing, complexes of both Ti(IV) and Zr(IV)
were generated by an analogous procedure and evalu-
ated in representative ac/acc sequences (Table 3). As is
evident from these examples, yields obtained for com-
plexes derived form Zr(IV) are comparable, or some-
times superior, to their Ti(IV) counterparts. It should
be noted that group IV complexes possessing compara-
tively electron deficient ligands (e.g., 1a , b, d , e, f, and
h ) are generally quite effective for the transformations
of interest. By way of contrast, Ti(IV) complexes bearing
conventional alkoxide (i-PrO, EtO), thioalkoxide (t-BuS),
fluoride, or g3 CH3 substituents are not useful for the
ac/acc sequence. As is expected from these trends, the
catechol-bearing zirconium alkyl 1j is considerably less
effective for the ac/acc reaction than its tetrachloro
counterpart 1h .
Ta ble 1. Am in oa lk yn e Cycliza tion Rea ction s
P r om oted by Com p lex 1a
Sch em e 2
We have previously shown that the presumed azati-
tanetine intermediate derived by the treatment of 3g
with CpTi(CH3)2Cl (8) could be efficiently trapped by
propionitrile (7) at slightly elevated temperatures.6c In
accord with this observation, sequential exposure of 3e
to 1a (0 °C f ambient) followed by 9 (1 equiv, 60 °C, 4
weeks) provided 7k in 84% isolated yield after quench-
1
2
ing (HClaq) (Scheme 3). The foregoing results are
consistent with the intermediacy of an azatitanetine
(
i.e., 4) in those reactions leading to efficient C-acylation.
cyclization/acyl cyanide coupling (ac/acc) reactions are
assembled in Table 2.
As we have previously noted for azatitanium intermedi-
ates derived from 8, N-acylation is the preferred
6a
Several of the above results are worthy of comment.
Whereas the Ti(IV) complex 1a is capable of eliciting
sequential ac/acc reactions involving 1-amino-4-alkynes
bearing aryl or trimethylsilyl substitution at the 5-posi-
tion (entries 2-9), 1-amino-4-alkynes possessing 5-alkyl
substituents undergo facile cyclization without success-
ful acylation when 1a is employed (entries 1 and 10).
By way of contrast, the reagent generated via sequential
treatment of 2 with CH3Li (3 equiv) followed by CF3-
reaction mode when acyl chlorides are used as trapping
reagents (Scheme 4).
In summation, we have shown that simple, non-Cp-
bearing organometallics of the type (CH3)2TiL1Cl‚2L2 (L1
) Cl, 1a ; OTFE, 1b) and the corresponding zirconium
complexes 1d , 1e, and 1h are highly effective reagents
for the aminoalkyne cyclization/acyl cyanide coupling
(10) For an additional example of transition metal modification by
trifluoroethoxy ligand substitution, see: Ryter, K.; Livinghouse, T. J .
Am. Chem. Soc. 1998, 120, 2658-2659.
1
0
CH2OH (TFEOH, 1 equiv), (CH3)2Ti(OTFE)Cl‚L2 (1b),
is capable of engaging in efficient ac/acc reactions with
the latter substrates (entries 11 and 12). As expected,
(
11) In consonance with these observations, a stoichiometric quan-
tity of CpTi(CH
b, leading to an azatitanium intermediate that failed to undergo clean
C-acylation in the presence of propanoyl cyanide.
12) In a control experiment, the attempted condensation of 3e with
mediated by TiCl ‚DME (2) (THF, 60 °C, 4 weeks) failed to produce
observable quantities of 7k .
3 2
)Cl was found to promote the efficient cyclization of
5
(CH3)TiCl3‚L2 (1c), generated by treatment of 2 with
(
only 1 equiv of CH3Li, gives rise to efficient cyclization
with minimal subsequent acyl cyanide interception
9
4

Synthetic Utility of Organometallic Reagents
Organometallics, Vol. 18, No. 21, 1999 4423
Ta ble 2. Am in oa lk yn e Cycliza tion /Acyl Cya n id e
Cou p lin g Rea ction s P r om oted by Non -Cp -Bea r in g
Ti(IV) Com p lexes
sequence. The active species 1a and 1b are highly
economical to prepare, and their use typically results
in superior product conversion than observed for CpTi-
6
a,d
(CH3)2Cl (8).
Exp er im en ta l Section 13
Dim eth yltita n iu m Dich lor id e (1a ) or Dim eth ylzir co-
n iu m Dich lor id e (1d ) Com p lex in THF . A flame-dried 5
mL test tube equipped with a magnetic Teflon-coated spinvane
was charged with TiCl
4
‚DME (2) (56 mg, 0.20 mmol) or ZrCl
4
(47 mg, 0.20 mmol) and fitted with a rubber septum. The test
tube was purged with argon, and THF (2 mL) was subse-
quently added. The reaction mixture was cooled to 0 °C, and
methyllithium (0.25 mL of 1.6 M in Et
was added dropwise via syringe. The solution was stirred for
5 min at 0 °C to produce a homogeneous orange solution for
2
O, 0.40 mmol, 2.0 equiv)
1
the titanium complex and a clear homogeneous solution for
the zirconium complex.
Dim eth yl(tr iflu or oeth oxy)tita n iu m Ch lor id e (1b) or
Dim eth yl(tr iflu or oeth oxy)zir con iu m (1e) Ch lor id e Com -
p lex in THF . A flame-dried 5 mL test tube equipped with a
magnetic Teflon-coated spinvane was charged with TiCl
4
‚DME
(
2) (56 mg, 0.20 mmol) or ZrCl (47 mg, 0.20 mmol) and fitted
4
with a rubber septum. The test tube was purged with argon,
and THF (2 mL) was subsequently added. The reaction
mixture was cooled to 0 °C, and methyllithium (0.38 mL of
1
2
.6 M in Et O, 0.60 mmol, 3.0 equiv) was added dropwise via
syringe. The reaction mixture was stirred for 15 min at 0 °C
followed by the addition of trifluoroethanol (20 mg, 0.20 mmol)
dissolved in THF (1 mL) and stirred for an additional 15 min
at 0 °C to produce a dark homogeneous solution for the
titanium complex and a clear homogeneous solution for the
zirconium complex.
2
,2-Dim eth yln on -4-yn yla m in e (3a ). A 50 mL flame-dried
round-bottomed flask equipped with a Teflon-coated magnetic
stirring bar was charged with a suspension of lithium alumi-
num hydride (0.23 g, 6.1 mmol) in Et O (25 mL) and fitted
2
with a rubber septum. The suspension was cooled to 0 °C and
treated with 2,2-dimethylnon-4-yne nitrile (1.0 g, 6.1 mmol)
dropwise over a 5 min period. Once the addition was complete,
the reaction mixture was warmed to ambient temperature and
stirred for an additional 8 h. The reaction mixture was cooled
to 0 °C, and a saturated ammonium chloride solution (5 mL)
was added to quench the unreacted lithium aluminum hydride,
2
followed by the addition of Et O (20 mL). The organic phase
was decanted from the aluminum salts, washed with brine,
dried over magnesium sulfate, filtered, and concentrated under
reduced pressure to give the crude product as a yellow oil. The
crude product was subjected to flash chromatography on silica
gel (5% EtOAc/hexane, then 15% MeOH/CH
2 2
Cl for elution)
to furnish the title amine (1.0 g, 97%) as a clear yellow liquid.
1
H NMR (300 MHz, CDCl
m, 2H, -CH CtC-), 1.98 (t, 2H, J ) 1.9 Hz, CCH
m, 4H, -CH CH -), 1.2 (bs, 2H, CH NH ), 0.84 (s, 9H, -Si-
C NMR (75 MHz, CDCl ): δ 81.82, 77.48, 52.19, 35.74,
1.21, 29.51, 24.49, 21.80, 18.22, 13.39. IR (film): 2959, 2932,
3
): δ 2.47 (s, 2H, -CH
2
NH
2
), 2.08
(
(
(
2
2
CH
2
), 1.43
2
2
2
2
1
3
CH
3
)
2
.
3
3
1
-
1
579, 1466, 1402, 1332, 1011 (cm ).
2
-Me t h y l-2-p h e n y l-5-(t r im e t h y ls ily l)p e n t -4-y n y l-
a m in e (3b). Subjecting 2-methyl-2-phenyl-5-(trimethylsilyl)-
pent-4-yne nitrile (5.0 g, 21 mmol) and lithium aluminum
hydride (0.79 g, 21 mmol) to the general procedure described
for 3a provided the title amine (3.7 g, 73%) as a yellow liquid.
1
H NMR (300 MHz, CDCl
3
): δ 7.34 (m, 4H, ArH), 7.18 (m,
), 2.86 (d, 1H,
), 2.62 (d, 1H, J ) 16.7 Hz, -CHHCt
a
∆1
1
2
3
4
1H, ArH), 3.07 (d, 1H, J ) 13.2 Hz, -CHHNH
J ) 13.2 Hz, -CHHNH
2
-Pyrrolines 5a and 5j (R ) n-C4H9, R ) CH3, R ) R )
5
2
R ) H) were obtained as the exclusive products in 84% (isolated)
b
1
1
and 89% (GC) yield, respectively. ∆ -Pyrrolines 5b and 5d (R
2
3
4
5
)
Ph, R ) H, R ) R ) CH3, R ) H) were obtained as the
(13) General experimental details may be found in ref 14.
exclusive products in 93% (isolated) and 78% (GC) yield, respec-
tively.
(14) Lee, C. H.; Westling, M.; Livinghouse, T.; Williams, A. C. J .
Am. Chem. Soc. 1992, 114, 4089.

4
424 Organometallics, Vol. 18, No. 21, 1999
Duncan and Livinghouse
Ta ble 3. Am in oa lk yn e Cycliza tion /Acyl Cya n id e Cou p lin g Rea ction s P r om oted by Alter n a tive
Non -Cp -Bea r in g Ti(IV) a n d Zr (IV) Com p lexes
Sch em e 3
3-Hyd r oxy-2,2-d im eth ylp en t-4-yn yln itr ile. A 100 mL
flame-dried round-bottomed flask equipped with rubber sep-
tum and a Teflon-coated magnetic stirring bar was charged
with a solution of LDA (prepared from diisopropylamine (2.97,
0
.03 mol) and n-BuLi (17.61 mL of 1.59 M in hexane, 0.03 mol))
in THF. The solution was cooled to 0 °C and treated with
isopropylnitrile (1.94 g, 0.03 mol). The reaction mixture was
stirred at 0 °C for 30 min and cooled to -78 °C, whereupon
3
-(trimethylsilyl)-2-propyn-1-al (7.5 g, 0.03 mol) in THF (50
CSi(CH
3
)
3
), 2.48 (d, 1H, J ) 16.7 Hz, -CHHCtCSi(CH
3
)
3
), 1.34
).
): δ 139.09, 128.77, 128.16, 125.68,
mL) was added dropwise over a 10 min period. The reaction
mixture was stirred for 3 h at -78 °C and then slowly warmed
to ambient temperature over a 2 h period. The solution was
cooled to 0 °C, a saturated ammonium chloride solution (25
mL) was added, and the mixture was stirred for an additional
(
s, 3H, -CH
3
), 1.09 (s, 2H, -NH
2
3 3
), 0.68 (s, 9H, -Si(CH )
1
3
C NMR (75 MHz, CDCl
3
1
3
22.57, 100.35, 89.81, 41.65, 34.02, 25.51, -0.23. IR (film):
088, 3059, 3025, 2959, 2173, 1249, 1026, 842 (cm ).
-
1

Synthetic Utility of Organometallic Reagents
Organometallics, Vol. 18, No. 21, 1999 4425
Sch em e 4
3
2
0 min. The reaction mixture was extracted with Et
5 mL), and the combined organic extracts were washed with
2
O (3 ×
25 mL), and the combined organic extracts were washed with
brine, dried over magnesium sulfate, and concentrated to give
a yellow oil. The residue was subjected to flash chromatogra-
phy on silica gel (20% ethyl acetate/hexane for elution) to
brine, dried over magnesium sulfate, and concentrated. The
residue was dissolved in methanol (10 mL) and treated with
a 5% NaOH/MeOH solution (5 mL). After stirring for 30 min
1
furnish the title compound as a colorless oil (1.31 g, 98%). H
the solution was concentrated, triturated with Et
2
O (10 mL),
NMR (300 MHz, CDCl
) 12.0 Hz, ArCHHO), 4.57 (d, 1H, J ) 12.0 Hz, ArCHHO),
3.97 (s, 1H, BnOCHCd), 1.41 (s, 3H, -C(CH )(CH )), 1.39 (s,
). C NMR (75 MHz,
): δ 137.6, 128.8, 128.3, 127.8, 122.9, 10.7, 94.4, 74.2,
71.5, 37.9, 23.2, 22.5, -0.1. IR (film): 2959, 2239, 2173 (cm ).
3-Ben zyloxy-2,2-d im eth yl-5-(tr im eth ylsilyl)p en t-4-yn -
yla m in e (3c). Subjecting 3-benzyloxy-2,2-dimethyl-5-(tri-
methylsilyl)pent-4-ynenitrile (0.80 g, 2.8 mmol) and lithium
aluminum hydride (0.11 g, 2.8 mmol) to the general procedure
3
): δ 7.36 (m, 5H, Ar H), 4.87 (d, 1H, J
and filtered through a pad of basic alumina. The filtrate was
concentrated, and the residue was subjected to flash chroma-
tography on silica gel (20% ethyl acetate/hexane for elution)
3
3
1
3
3H, -C(CH
CDCl
3 3 3 3
)(CH )), 0.19 (s, 9H, Si(CH )
1
to furnish the title nitrile (3.14 g, 88%) as a clear liquid. H
3
-1
NMR (250 MHz, CDCl
OH), 2.56 (s, 1H, -CtCH), 1.44 (s, 6H, -C(CH
75 MHz, CDCl ): δ 119.5, 85.1, 75.2, 68.6, 34.8, 16.0. IR
film): 3412, 3273, 2983, 2245, 2124 (cm ).
-Ben zyloxy-2,2-d im eth ylp en t-4-yn yln itr ile. A 50 mL
3
): δ 4.24 (s, 1H, CHOH), 2.92 (bs, 1H,
1
3
-
3 2
) ). C NMR
(
(
3
-
1
3
flame-dried round-bottomed flask equipped with a Teflon-
coated magnetic stirring bar was charged with a suspension
of NaH (0.65 g, 16.10 mmol) in THF (20 mL) and fitted with
a rubber septum. The reaction mixture was cooled to 0 °C and
treated with 3-hydroxy-2,2-dimethylpent-4-ynylnitrile (1.0 g,
described for 3a provided the title amine (0.72 g, 69%) as a
1
viscous colorless oil. H NMR (300 MHz, CDCl
3
): δ 7.36-7.29
(m, 5H, Ar H), 4.82 (d, 1H, J ) 11.9 Hz, OCHHPh), 4.45 (d,
1H, J ) 11.9 Hz, OCHHPh), 3.84 (s, 1H, CHOCH Ph) 2.67 (d,
1H, J ) 13.3 Hz, CHHNH ), 2.57 (d, 1H, J ) 13.3 Hz,
CHHNH ), 1.41 (bs, 2H, -NH ), 0.95 (s, 3H, C(CH )(CH )), 0.92
(s, 3H, C(CH )(CH )), 0.18 (s, 9H, Si(CH ). C NMR (75 MHz,
CDCl ): δ 11.04, 85.24, 51.02, 37.16, 33.51, 22.20, 21.63, 15.25,
0.53, 0.18. IR (film): 3396, 3064, 2957, 2887, 2167, 1652, 1608,
2
2
8
.12 mmol) dissolved in THF (5 mL) over a 10 min period. Once
2
2
3
3
1
3
the addition was complete, the reaction mixture was stirred
for 2 h at ambient temperature and then treated with benzyl
bromide (2.78 g, 16.24 mmol). After stirring for 12 h, a
3
3
3 3
)
3
-
1
saturated K
2
CO
3
solution (5 mL) was added, and the mixture
1496, 1454, 1386, 1249, 1069, 840, 759, 697 (cm ).
was extracted with Et
2
O (3 × 25 mL). The combined organic
2,2-Dim eth yl-5-p h en yl-4-p en tyn yla m in e (3d ). Subject-
ing 5-phenyl-2,2-dimethyl-5-phenylpent-4-ynenitrile (1.0 g, 5.5
mmol) and lithium aluminum hydride (0.21 g, 5.5 mmol) to
the general procedure described for 3a provided the title amine
(0.87 g, 84%) as clear yellow liquid. 1H NMR (300 MHz,
extracts were washed with brine, dried over magnesium
sulfate, and concentrated. The residue was subjected to flash
chromatography on silica gel (20% ethyl acetate/hexane for
elution) to furnish the title compound (1.19 g, 69%) as a clear
1
liquid. H NMR (300 MHz, CDCl
3
): δ 7.34 (m, 5H, Ar H), 4.90
CDCl
-CH
(s, 6H, -C(CH
3
): δ 7.37 (m, 2H, ArH), 7.15 (m, 3H, ArH), 2.60 (s, 2H,
NH ), 2.31 (s, 2H, CH CtCPh), 1.37 (bs, 2H, -NH ), 0.99
). C NMR (75 MHz, CDCl ): δ 131.95,
(
d, 1H, J ) 12.0 Hz, ArCHHO), 4.86 (d, 1H, J ) 12.0 Hz,
ArCHHO), 3.98 (d, 1H, J ) 2.1 Hz, BnOCHCd), 2.59 (d, 1H,
J ) 2.1 Hz, -CdCH), 1.43 (s, 3H, -C(CH )(CH )), 1.41 (s, 3H,
)). C NMR (75 MHz, CDCl ): δ 137.1, 128.9,
2
2
2
2
1
3
3
)
2
3
3
3
128.59, 127.96, 126.4, 52.49, 35.96, 30.45, 25.11. IR (film):
1
3
-1
-
C(CH
3
)(CH
3
3
3280, 3067, 2953, 2859, 1599, 1575, 750, 681 (cm ).
1
3
28.5, 128.4, 123.4, 78.4, 73.2, 71.5, 38.1, 23.6, 22.7. IR (film):
2,2-Dim eth yl-5-(tr im eth ylsilyl)p en t-4-yn yla m in e (3e).
Subjecting 2,2-dimethyl-5-(trimethylsilyl)pent-4-ynenitrile (0.41
g, 3.0 mmol) and lithium aluminum hydride (0.11 g, 3.0 mmol)
to the general procedure described for 3a provided the title
280, 2975, 2855, 2234, 2114 (cm-1).
3
-Be n zyloxy-2,2-d im e t h yl-5-(t r im e t h ylsilyl)p e n t -4-
yn yln itr ile. A 50 mL flame-dried round-bottomed flask
equipped with a rubber septum and a Teflon-coated magnetic
stirring bar was charged with a solution of LDA (prepared from
diisopropylamine (0.47 g, 4.69 mol) and n-BuLi (2.95 mL of
1
amine (0.36 g, 76%) as a yellow liquid. H NMR (300 MHz,
CDCl
1.31 (bs, 2H, -CH
-CtCSi(CH
3
): δ 2.48 (s, 2H, -CH
NH ), 0.86 (s, 6H, C(CH
). C NMR (75 MHz, CDCl ): δ 105.0, 86.2,
51.8, 30.4, 25.2, 24.4, 0.0. IR (film): 2959, 2173, 1579, 1469,
2
NH
2
), 2.05 (s, 2H, -CH
2
CtC),
), 0.08 (s, 9H,
2
2
3 2
)
1
3
1
.59 M in hexane, 4.69 mmol)) in THF (20 mL). The solution
3
)
3
3
was cooled to 0 °C, and 3-benzyloxy-2,2-dimethylpent-4-
ynylnitrile (1.20 g, 4.69 mmol) was added dropwise over a 10
min period. The reaction mixture was stirred at 0 °C for 1 h
and cooled to -78 °C, whereupon chlorotrimethylsilane (0.54
g, 5.00 mmol) in THF (5 mL) was added. The reaction mixture
was stirred for 3 h at -78 °C and then slowly warmed to
ambient temperature over a 2 h period. The mixture was
cooled to 0 °C, and a saturated ammonium chloride solution
-
1
1249, 1038, 842 (cm ).
2,2,3-Tr im eth yl-5-(tr im eth ylsilyl)pen t-4-yn ylam in e (3f).
Subjecting 3,2,2-trimethyl-5-(trimethylsilyl)pent-4-ynenitrile
(0.84 g, 4.3 mmol) and lithium aluminum hydride (0.17 g, 4.3
mmol) to the general procedure described for 3a provided the
1
title amine (0.74 g, 87%) as a viscous colorless oil. H NMR
(300 MHz, CDCl
(q, 1H, J ) 7.1 Hz, CHCH
CHHNH ), 1.10 (d, 3H, J ) 7.1 Hz, CHCH
3
): δ 2.65 (d, 1H, J ) 12.8 Hz, CHHNH
), 2.45 (d, 1H, J ) 12.8 Hz,
), 0.97 (s, 3H,
2
), 2.56
(25 mL) was added with subsequent stirring for an additional
3
3
0 min. The reaction mixture was extracted with Et
2
O (3 ×
2
3

4
426 Organometallics, Vol. 18, No. 21, 1999
Duncan and Livinghouse
C(CH
0
8
3
)(CH
.24 (s, 9H, Si(CH
5.24, 51.02, 37.16, 33.51, 22.20, 21.63, 15.25, 0.53, 0.18. IR
3
)), 0.95 (bs, 2H, -NH
2
), 0.85 (s, 3H, C(CH
3
)(CH
3
)),
37.53, 36.52, 32.36, 28.15, 22.63, 22.06, 16.78, 13.90, 0.14. IR
(neat): 3320, 3285, 2959, 2861, 2173, 1590, 1460, 1370, 825
)
3
). 13C NMR (75 MHz, CDCl
3
): δ 111.04,
3
-
1
cm
.
(
film): 2963, 2203, 1599, 1461, 1252, 1049, 1038, 854, 751, 694
3,3-Dim et h yl-5-p en t yl-3,4-d ih yd r o-2H -p yr r ole (5a ).6a
Subjecting 3a (38 mg, 0.20 mmol) to the general procedure
for 5b provided the title compound (36 mg, 84%) as a yellow
oil with no additional purification required. 1H NMR (300
-
1
(cm ).
5
-P h en ylp en t-4-yn yla m in e (3 g). A 50 mL flame-dried
round-bottomed flask equipped with a Teflon-coated magnetic
stirring bar was charged with a suspension of potassium
phthalimide (1.4 g, 7.4 mmol) in dimethylformamide (25 mL)
and fitted with a rubber septum. The reaction mixture was
treated with 1-iodo-5-phenyl-4-pentyne (2.0 g, 7.4 mmol) and
heated at 60 °C with stirring for 12 h. Dimethylformamide
was removed under reduced pressure, and the resulting
residue was triturated with 10% aqueous potassium hydroxide
MHz, CDCl
dCCH CH ), 2.21 (s, 2H, dCCH
.31 (m, 4H, CH CH CH ), 1.02 (s, 6H, C(CH
). C NMR (75 MHz, CDCl ): δ 178.13, 74.24, 52.26,
3
): δ 3.49 (s, 2H, dNCH
C), 1.51 (m, 2H, CH
), 0.83 (m, 3H,
2
), 2.26 (t, 2H, J ) 1.5 Hz,
2
3
2
2
CH CH ),
2
2
1
-
3
2
2
2
2
3 2
)
1
3
CH
2
CH
3
3
8.31, 34.70, 28.08, 26.00, 22.43, 13.92. IR (film): 2956, 2926,
-
1
8.56, 1651, 1576, 1463, 1256 cm
.
3
-Met h yl-3-p h en yl-3,4-d ih yd r o-2H -p yr r ole (5b ).6a
A
flame-dried 5 mL test tube with a magnetic Teflon-coated
spinvane was charged with TiCl ‚DME (2) (56 mg, 0.20 mmol)
(
2 × 25 mL) to afford a white solid after filtration (1.53 g, 71%).
4
The white solid was dissolved in ethanol (100%, 25 mL) and
treated with hydrazine monohydrate (0.27 g, 5.29 mmol). The
reaction flask was fitted with a reflux condenser, and the
solution was heated at reflux for 8 h, during which time a
white solid precipitated. Upon cooling to ambient temperature,
the solid was collected by filtration and washed several times
and fitted with a rubber septum. The test tube was purged
with argon, and THF (2 mL) was subsequently added. The
solution was cooled to 0 °C, and methyllithium (0.27 mL of
1
2
.5 M in Et O, 0.40 mmol, 2.0 equiv) was added dropwise via
syringe. Once the addition was complete, the reaction mixture
was stirred for 30 min at 0 °C and then treated with 2-methyl-
with Et
2
O (3 × 50 mL). The filtrate was concentrated under
2
-phenyl-5-(trimethylsilyl)pent-4-ynylamine (3b) (49 mg, 0.20
reduced pressure to give a cloudy oil, which was purified by
bulb-to-bulb distillation (110 °C at 0.25 mmHg) to furnish the
title compound (0.79 g, 64%) as a colorless oil. H NMR (300
mmol). The test tube was wrapped in aluminum foil and
allowed to warm to ambient temperature and stirred for 3 h.
A 5% sodium hydroxide/methanol solution (1 mL) was added
to the reaction mixture, which was stirred for an additional
1
MHz, CDCl
t, 2H, J ) 6.80 Hz, -NCH
CPh), 1.71 (m, 2H, -CH CH
NMR (75 MHz, CDCl ): δ 131.55, 128.17, 127.53, 124.00,
9.61, 80.97, 41.36, 32.60, 16.88. IR (film): 3298, 3056, 2938,
3
): δ 7.35 (m, 2H, ArH), 7.24 (m, 3H, ArH), 2.83
), 2.45 (t, 2H, J ) 7.0 Hz, -CH Ct
CH ), 1.16 (bs, 2H, -NH
). 13
(
2
2
2
0 min. The reaction mixture was filtered through a small pad
2
2
2
2
C
of silica gel (Et O for elution) and concentrated in vacuo to
2
1
3
provide the title compound as a yellow oil (32 mg, 93%). H
8
2
NMR (300 MHz, CDCl ): δ 7.33 (m, 3H, ArH), 7.21 (m, 2H,
3
-
1
866, 2228, 1598, 1570, 1560, 1490, 1442, 756 (cm ).
ArH), 3.97 (s, 2H, dNCH ), 2.90 (d, 1H, J ) 16.9 Hz, dCCHH),
2
1
-Bu tyl-5-(tr im eth ylsilyl)p en t-4-yn yla m in e (3h ). A 250
2.66 (d, 1H, J ) 16.9 Hz, dCCHH), 2.06 (s, 3H, dCCH
3
), 1.34
): δ 174.71, 149.13,
28.87, 126.32, 126.22, 74.50, 53.83, 47.26, 30.30, 20.6. IR
neat): 2956, 2921, 2861, 1646, 1495, 1430, 1377, 1309, 1029,
1
3
mL flame-dried round-bottomed flask equipped with a mag-
netic Teflon-coated stirring bar was charged with diisopropyl-
amine (2.6 g, 20 mmol) dissolved in THF (100 mL) and fitted
with a rubber septum. The mixture was cooled to 0 °C and
treated with n-BuLi (10.4 mL of 2.21 M in hexane, 20 mmol)
dropwise over a 5 min period. The reaction was cooled to -50
3 3
(s, 3H, -CCH ). C NMR (75 MHz, CDCl
1
(
7
-
1
62, 700 cm
.
4
-Ben zyloxy-3,3,5-tr im eth yl-3,4-d ih yd r o-5-m eth yl-2H-
p yr r ole (5c). Subjecting 3c (38 mg, 0.20 mmol) to the general
procedure for 5b provided the title compound (36 mg, 84%) as
°
2
C, and 9-(trimethylsilyl)non-8-yn-5-one-O-(tetrahydropyran-
1
6
b
a yellow oil with no additional purification required. H NMR
-yl)oxime (3.0 g, 15 mmol) in THF (10 mL) was added and
(
300 MHz, CDCl
Hz, PhCHHO), 4.59 (d, 1H, J ) 11.7 Hz, PhCHHO), 3.94 (s,
H, OCHCd), 3.51 (d, 1H, J ) 10.1 Hz, dNCHH), 3.39 (d, 1H,
), 1.19 (s, 3H,
)). C NMR (75 MHz,
): δ 176.15, 138.4, 128.86, 128.30, 128.24, 93.06, 73.99,
3
): δ 7.30 (m, 5H, ArH), 4.74 (d, 1H, J ) 11.7
stirred for an additional 4 h. 3-(Trimethylsilyl)propargyl
bromide (2.9 g, 15 mmol) was added, and the reaction mixture
was allowed to warm to ambient temperature over a 5 h period.
A solution of saturated aqueous ammonium chloride (50 mL)
1
J ) 10.1 Hz, NCHH-), 1.99 (s, 3H, dCCH
C(CH )(CH )), 1.01 (s, 3H, C(CH )(CH
3 3 3 3
CDCl
3
1
3
2
and Et O (50 mL) was successively added to the reaction
3
mixture, which was stirred for an additional 20 min. The
biphasic mixture was transferred to a separatory funnel, and
the phases were separated. The aqueous phase was re-
extracted with Et
extracts were washed with brine, dried over magnesium
sulfate, filtered, and concentrated. The residue was dissolved
7
2.18, 26.97, 21.80, 18.24. IR (film): 3334, 2981, 2361, 1626,
-
1
1
481, 1377, 1309, 754, 730 cm . HRMS (CI): m/z 218.1534
20NO, 218.1544).
-(4,4-Dim eth yl-pyr r olidin e-2-yliden e)octan -3-on e (7a).
Meth od A. A flame-dried 5 mL test tube with a magnetic
Teflon-coated spinvane was charged with TiCl ‚DME (2) (56
(calculated for (M + 1) C14H
2
O (2 × 50 mL), and the combined organic
6
a
4
4
in Et
2
O (50 mL) and added via cannula to a suspension of
O (50 mL)
mg, 0.20 mmol) and fitted with a rubber septum. The test tube
was purged with argon, and THF (2.0 mL) was subsequently
added. The reaction mixture was cooled to 0 °C and treated
lithium aluminum hydride (0.56 g, 7.8 mmol) in Et
2
at -78 °C. Once the addition was complete, the reaction
mixture was allowed to warm to ambient temperature and
stirred for an additional 8 h. The reaction mixture was cooled
to 0 °C, and a solution of saturated ammonium chloride (NH
Cl) was added to quench the unreacted lithium aluminum
hydride, followed by the addition of Et O (50 mL). The organic
2
with methyllithium (0.40 mL of 1.5 M in Et O, 0.60 mmol, 3.0
equiv) dropwise over a 2 min period. The reaction was stirred
for 15 min at 0 °C followed by the addition of 2,2,2-trifluoro-
ethanol (20 mg, 0.20 mmol) and was subsequently stirred for
an additional 15 min at 0 °C. 2,2-Dimethylnon-4-ynylamine
4
-
2
phase was decanted from the aluminum salts, washed with
brine, dried over magnesium sulfate, filtered, and concentrated
under reduced pressure to give the crude product as a yellow
oil. The crude product was subjected to flash chromatography
(
3a ) (34 mg, 0.20 mmol) was added, and the test tube was
wrapped in aluminum foil and allowed to warm to ambient
temperature with stirring for an additional 3 h. The reaction
mixture was cooled to 0 °C and treated with propanoylnitrile
(17 mg, 0.20 mmol). The reaction mixture was allowed to warm
to ambient temperature and stirred for 72 h. Methanol (1.0
mL) was added, and the reaction mixture was stirred for 20
on silica gel (5% EtOAc/hexane, then 15% MeOH/CH
2 2
Cl for
elution) to furnish the title amine (1.0 g, 77%) as a clear yellow
1
liquid. H NMR (300 MHz, CDCl
3
): δ 3.57 (m, 1H, CH
CtC-), 1.72 (bs, 2H, -NH
), 0.87 (m, 3H, CH CH ), 1.41 (s, 9H, Si-
). 13C NMR (75 MHz, CDCl
): δ 107.11, 84.70, 50.39,
2
CHNH
2
),
2
1
.26 (t, J ) 7.2 Hz, 2H, CH
.72 (m, 8H, 4-CH
2
2
), 1.35-
min. The solution was filtered through a pad of silica gel (Et O
2
for elution) and concentrated in vacuo. The residue was
subjected to column chromatography (30% ethyl acetate/
2
2
3
(CH
3
)
3
3

Synthetic Utility of Organometallic Reagents
Organometallics, Vol. 18, No. 21, 1999 4427
hexane for elution) to provide the title compound as a slightly
yellow oil (32 mg, 71%).
Meth od B. Subjecting 3a (38 mg, 0.20 mmol) to the general
198.34, 166.66, 140.54, 132.30, 128.73, 126.75, 106.57, 60.94,
47.59, 36.98, 33.16, 27.28, 9.92. IR (KBr): 3446, 2958, 2869,
2364, 2344, 1632, 1567, 1459, 1420, 1185, 1019 cm .
1-(4,4-Dim eth ylpyr r olidin e-2-ylidene)butane-2-one (7e).6a
-
1
procedure for 7a [except ZrCl
instead of TiCl ‚DME (2)] provided the title compound as a
slightly yellow oil (37 mg, 81%). H NMR (300 MHz, CDCl
δ 10.21 (bs, 1H, -NH), 3.25 (s, 2H, -NCH ), 2.41 (s, 2H,
dCCH ), 2.39 (q, 2H, J ) 7.4 Hz, -OCCH CH ), 2.11 (t, 2H, J
7.5 Hz, dC-CH CH -), 1.29 (m, 4H, -CH CH -), 1.12 (s,
H, C(CH ), 1.07 (t, 3H, J ) 7.4 Hz, -OCCH CH ), 0.89 (t,
H, J ) 6.7 Hz, -CH ). C NMR (75 MHz, CDCl ): δ
4
(76 mg, 0.2 mmol) was used
4
Subjecting 3e (37 mg, 0.20 mmol) to the general procedure
for 7b provided the title compound as a yellow oil (28 mg, 83%)
after the crude material was subjected to flash chromatogra-
1
3
):
2
1
2
2
3
phy (20% ethyl acetate/hexane for elution). H NMR (300 MHz,
): δ 9.62 (bs, 1H, -NH), 5.03 (s, 1H, CdCH), 3.26 (bs,
H, -CH N-), 2.34 (s, 2H, CdCH ), 2.25 (q, 2H, J ) 7.6 Hz,
OCCH CH )1.12 (s, 3H, C(CH )(CH )), 1.11 (s, 3H, C(CH )(CH )),
.08 (t, 3H, J ) 7.6 Hz, OCCH ). C NMR (75 MHz,
)
2
2
2
2
6 6
C D
6
3
1
2
1
3
)
2
2
3
2
2
2
1
3
2
CH
3
3
2
3
3
3
3
3
99.00, 166.44, 101.71, 60.54, 46.37, 36.90, 34.55, 31.42, 29.09,
7.48, 23.21, 14.42, 10.01. IR (film): 2957, 2929, 2870, 1617,
539, 1180 cm
13
1
2 3
CH
CDCl
3
): δ 199.1, 167.1, 89.1, 60.2, 47.0, 36.7, 34.7, 26.8, 10.1.
-
1
.
-1
IR (film): 2959, 2931, 2870, 1624, 1560, 1502, 1465 cm
.
1
-(4-Meth yl-4-p h en yl-p yr r olid in e-2-ylid en e)bu ta n e-2-
1
-(3,4,4-Tr im e t h ylp yr r olid in e -2-ylid e n e )b u t a n e -2-
6
a
on e (7b). A flame-dried 5 mL test tube equipped with a
Teflon-coated magnetic spinvane was charged with TiCl ‚DME
2) (56 mg, 0.20 mmol) and fitted with a rubber septum. The
on e (7f). Subjecting 3f (118 mg, 0.600 mmol) to the general
procedure for 7b provided the title compound as a white solid
4
(
(77.0 mg, 71%) after the crude material was subjected to flash
test tube was purged with argon, and THF (2.0 mL) was
subsequently added. The reaction mixture was cooled to 0 °C
chromatography (20% ethyl acetate/hexane for elution). Mp:
1
8
4
7
1-83 °C. H NMR (300 MHz, CDCl
.99 (s, 1H, CdCH), 3.21 (bs, 2H, -CH
.2 Hz, CH CH-), 2.29 (q, 2H, J ) 7.6 Hz, OCCH
)(CH )), 1.09 (t, 3H, J ) 7.6 Hz, OCCH
.02 (d, 3H, J ) 7.2 Hz, CH CH-), 0.89 (s, 3H, C(CH )(CH
): δ 199.90, 171.45, 88.38, 59.45,
3
): δ 9.55 (bs, 1H, -NH),
N-), 2.37 (q, 1H, J )
CH ), 1.09
CH ),
)).
and treated with methyllithium (0.27 mL of 1.5 M in Et
2
O,
2
0
.40 mmol, 2.0 equiv) to give an orange, homogeneous solution.
3
2
3
The reaction mixture was stirred for 30 min at 0 °C and treated
with 2-methyl-2-phenyl-5-(trimethylsilyl)pent-4-ynylamine (49
mg, 0.20 mmol). The test tube was wrapped in aluminum foil
and allowed to warm to ambient temperature with vigorous
stirring for 3 h. The reaction mixture was cooled to 0 °C and
treated with propanoyl nitrile (17 mg, 0.20 mmol). The reaction
mixture was allowed to warm to ambient temperature and
stirred for 72 h. Methanol (1.0 mL) was added, and the reaction
mixture was stirred for an additional 20 min, filtered through
(
s, 3H, C(CH
3
3
2
3
1
3
3
3
13
C NMR (75 MHz, CDCl
3
4
2
1
8.90, 35.28, 25.81, 21.56, 11.15, 10.57. IR (KBr): 3335, 2962,
870, 1731, 1623, 1560, 1494, 1458, 1370, 1279, 1200, 1151,
-1
019 cm . HRMS (EI): m/z 181.1462 (calculated for C17
23
H -
NO
2
, C11
H
19NO, 181.1467).
1
-(P yr r olid in e-2-ylid en e)bu ta n e-1-p h en yl-2-on e (7g).6a
Subjecting 3g (32 mg, 0.20 mmol) to the general procedure
for 7b provided the title compound as a yellow oil (36 mg, 83%)
after the crude material was subjected to flash chromatogra-
2
a pad of silica gel (Et O for elution), and concentrated in vacuo.
The residue was subjected to column chromatography (30%
ethyl acetate/hexane for elution) to provide the title compound
1
1
phy (30% ethyl acetate/hexane for elution). H NMR (300 MHz,
as a slightly yellow oil (40 mg, 87%). H NMR (300 MHz,
CDCl
3
): δ 10.45 (bs, 1H, -NH), 7.34-7.17 (m, 3H, ArH), 7.16-
.14 (m, 2H, ArH), 3.63 (t, 2H, J ) 7.2 Hz, -NCH ), 2.35 (t,
H, J ) 7.8 Hz, dCCH CH -), 2.13 (q, 2H, J ) 7.4 Hz, OCCH
), 1.88 (q, 2H, J ) 7.8 Hz, -CH CH CH -), 0.99 (t, 3H, J
). C NMR (75 MHz, CDCl ): δ 197.74,
166.49, 140.27, 131.85, 128.30, 126.35, 105.7247.84, 32.62,
CDCl
3
): δ 9.72 (bs, 1H, -NH), 7.35-7.29 (m, 2H, ArH), 7.25-
7
2
2
7
.18 (m, 3H, ArH), 5.16 (s, 1H, CdCH), 3.81 (d, 1H, J ) 10.4
2
2
2
-
Hz, -NCHH), 3.66 (d, 1H, J ) 10.4 Hz, -NCHH), 3.01 (d, 1H,
J ) 16.1 Hz, dCCHH), 2.69 (d, 1H, J ) 16.1 Hz, dCCHH),
CH
7.4 Hz, OCCH
3
2
2
2
1
3
)
2
CH
3
3
2
3
1
4
1
.31 (q, 2H, J ) 7.5 Hz, -CH
). 1 C NMR (75 MHz, CDCl
3
2
CH
3
), 1.4 (s, 3H, -CH
3
), 1.09 (t,
3
H, J ) 7.5 Hz, -CH CH
2
3
): δ
2
cm
9.66, 21.40, 9.52. IR (film): 3277, 2925, 1615, 1538, 1198
99.82, 166.63, 146.93, 129.08, 126.96, 126.02, 89.83, 59.79,
6.28, 44.78, 35.16, 29.40, 10.51. IR (film): 3310, 2964, 2931,
-
1
.
1-(5-Bu t yl-p yr r olid in e-2-ylid en e)b u t a n e-2-on e (7h ).6a
Subjecting 3h (42 mg, 0.20 mmol) to the general procedure
627, 1557, 1225, 1017 cm-1
.
1
-(3-Be n zyloxy-4,4-d im e t h yl-p yr r olid in -2-ylid e n e )-
(except the cyclization step required stirring for 24 h at
bu ta n -2-on e (7c). Subjecting 3c (232 mg, 0.800 mmol)) to the
general procedure for 7b provided the title compound as a
white solid (160 mg, 73%) after the crude material was
ambient temperatures in order to complete cyclization) for 7b
provided the title compound as a yellow oil (31 mg, 79%) after
the crude material was subjected to flash chromatography
(20% ethyl acetate/hexane for elution). 1H NMR (300 MHz,
subjected to flash chromatography (20% ethyl acetate/hexane
1
for elution). Mp: 110-112 °C. H NMR (300 MHz, CDCl
3
): δ
C
(
(
6
D
6
): δ 10.35 (bs, 1H, -NH), 5.14 (s, 1H, dCHCO-), 3.19
m, 1H, -CHN-), 2.48 (q, 2H, J ) 7.6 Hz, OCCH CH ), 2.21
m, 2H, CH Cd), 1.36 (t, 3H, J ) 7.6 Hz, OCCH CH ), 1.13-
.04 (m, 8H, CH pocket), 0.82 (t, 3H, J ) 7.21 Hz, CH CH ).
C NMR (75 MHz, CDCl ): δ 198.14, 165.65, 88.86, 60.09,
6.10, 35.33, 31.84, 28.81, 28.01, 23.00, 14.24, 10.64. IR
9
4
.28 (bs, 1H, -NH), 7.35 (m, 5H, Ar H), 5.20 (s, 1H, dCHCO-),
.74 (d, 1H, J ) 11.8 Hz, PhCHHO-), 4.64 (d, 1H, J ) 11.8
2
3
Hz, PhCHHO-), 3.88 (s, 1H, OCHCd), 3.31 (d, 1H, J ) 10.5
Hz, CHHNH), 3.17 (d, 1H, J ) 10.5 Hz, CHHNH), 2.36 (q,
2
2
3
1
2
2
3
1
3
2
H, J ) 7.6 Hz, COCH
OCCH CH ), 1.15 (s, 3H, C(CH
). C NMR (75 MHz, CDCl
3
2 3
CH
), 1.09 (t, 3H, J ) 7.6 Hz,
)CH ), 1.07 (s, 3H, C(CH )-
): δ 209.47, 165.14, 138.25,
3
3
2
3
3
3
3
-
1
1
3
(film): 2960, 2933, 2871, 1621, 1934, 1180, 1015 cm .
CH
3
1
2
1
2
28.84, 128.25, 90.23, 87.59, 73.48, 58.13, 41.80, 35.44, 25.45,
1-P h en yl-2-(4-m eth yl-4-p h en yl-p yr r olid in e-2-ylid en e)-
eth a n on e (7i). Subjecting 3b (0.49 g, 2.0 mmol) to the general
procedure for 6b (except benzoyl nitrile was used as the
trapping reagent) provided the title compound as a white solid
(0.34 g, 62%) after the crude material was subjected to flash
0.37, 10.29, -0.84. IR (KBr): 3308, 2960, 1635, 1567, 1497,
-
1
457, 1343, 1284, 1218, 1128, 1026 cm . HRMS (EI): m/z
73.1733 (calculated for C17
2
H23NO , 273.1729).
1
-(4,4-Dim eth ylpyr r olidin e-2-yliden e)-1-ph en ylbu tan e-
6
a
2
-on e (7d ). Subjecting 3d (38 mg, 0.20 mmol) to the general
chromatography (20% ethyl acetate/hexane for elution). Mp:
1
procedure for 7b provided the title compound as a white
64-66 °C. H NMR (300 MHz, CDCl
3
): δ 10.45 (bs, 1H, -NH),
crystalline solid (35 mg, 72%) after the crude material was
subjected to flash chromatography (30% ethyl acetate/hexane
8.32 (m, 2H, ArH), 7.33-7.07 (m, 6H, ArH), 6.93 (m, 2H, ArH),
5.96 (s, 1H, CdCH), 3.24 (d, 1H, J ) 10.5 Hz, CHH NH), 2.96
(d, 1H, J ) 10.5 Hz, CHH NH), 2.69 (d, 1H, J ) 16.0 Hz,
CCHHCd), 2.35 (d, 1H, J ) 16.0 Hz, CCHHCd), 1.09 (s, 3H,
2
1
for elution). Mp: 82-84 °C. H NMR (300 MHz, CDCl
3
): δ
2
1
2
2
3
0.13 (bs, 1H, -NH), 7.33-7.22 (m, 3H, ArH), 7.15-7.12 (m,
1
3
H, ArH), 3.34 (s, 2H, -NCH
H, J ) 7.5 Hz, OCCH CH ), 1.06 (s, 6H, C(CH
H, J ) 7.5 Hz, OCCH CH
2
), 2.11 (s, 2H, dCCH
2
), 2.09 (q,
), 0.96 (t,
3 3
CPh(CH )). C NMR (75 MHz, CDCl ): 188.35, 167.16, 147.08,
2
3
3
)
2
141.37, 130.85, 128.91, 128.63, 126.75, 126.01, 87.45, 59.45,
59.24, 46.28, 44.25, 28.69. IR (KBr): 3317, 2936, 2931, 1617,
1
3
2
3
). C NMR (75 MHz, CDCl
3
): δ

4
1
428 Organometallics, Vol. 18, No. 21, 1999
Duncan and Livinghouse
527, 1245, 1017, 754 cm-1. HRMS (EI): m/z 277.1460
septum. The test tube was purged with argon, and THF (2.0
mL) was subsequently added. The reaction mixture was cooled
to 0 °C and then treated with methyllithium (0.27 mL of 1.5
(calculated for C14
H17NO, 277.1467).
6
a
4
-(3-Meth ylpyr r olidin e-2-yliden e)octan -3-on e (7j). Sub-
jecting 3-methylnon-4-ynylamine (26 mg, 0.17 mmol) to the
general procedure for 7a provided the title compound as a
yellow oil (26 mg, 62%) after the crude material was subjected
M in Et O, 0.40 mmol, 2.0 equiv) to give an orange, homoge-
2
neous solution. The reaction mixture was stirred for 30 min
at 0 °C and then treated with 2-methyl-2-phenyl-5-(trimeth-
ylsilyl)pent-4-ynylamine (49 mg, 0.20 mmol). The test tube was
wrapped in aluminum foil and allowed to warm to ambient
temperature with vigorous stirring for 3 h. The reaction
mixture was cooled to 0 °C and treated with methyl chloro-
formate (19 mg, 0.20 mmol). The reaction mixture was allowed
to warm to ambient temperature and was stirred for 18 h.
Methanol (10 µL) and hexane (2 mL) were added to the
mixture, which was stirred for an additional 20 min, filtered
to flash chromatography (20% ethyl acetate/hexane for elu-
1
tion). H NMR (300 MHz, CDCl
(
3
): δ 10.42 (bs, 1H, -NH), 3.96
), 2.39 (q, 2H, J ) 7.39
), 2.10 (m, 2H, dCCH CH -), 1.47 (m, 1H,
), 1.28 (m, 4H, -CH CH -), 1.21 (d, 3H, J ) 6.3 Hz,
), 1.07 (t, 3H, J ) 7.4 Hz, OCCH CH ), 0.89 (t, 3H, J
). C NMR (75 MHz, CDCl ): δ 198.39,
m, 1H, -NCH), 2.67 (m, 2H, dCCH
Hz, OCCH CH
CHCH
CHCH
2
2
3
2
2
-
-
)
3
3
2
2
2
3
1
3
7.1 Hz, -CH
2
CH
3
3
1
2
1
65.39, 100.54, 55.44, 33.88, 31.13, 30.89, 29.72, 28.52, 22.80,
1.66, 13.90, 9.45. IR (film): 3246, 2961, 2931, 2871, 1616,
through a pad of silica gel (Et
in vacuo. The residue was subjected to column chromatography
10% ethyl acetate/hexane for elution) to provide the title
2
O for elution), and concentrated
-
1
535, 1187 cm
-(4,4-Dim eth ylp yr r olid in e-2-ylid en e)-3-m eth ylbu ta n -
-on e (7k ). A flame-dried 5 mL test tube with a screw top
.
1
(
2
1
compound as a slightly yellow oil (35 mg, 76%). H NMR (300
MHz, CDCl ): δ 7.30-7.19 (m, 5H, ArH), 4.95 (d, 1H, J ) 1.3
Hz, CH)C), 3.88 (d, 1H, J ) 11.2 Hz, NCHH), 3.85 (d, 1H, J
equipped with a Teflon-coated magnetic spinvane was charged
with TiCl ‚DME (2) (56 mg, 0.20 mmol) and fitted with a
rubber septum. The test tube was purged with argon, and THF
2 mL) was subsequently added. The reaction mixture was
cooled to 0 °C, and methyllithium (0.27 mL of 1.5 M in Et O,
.40 mmol, 2.0 equiv) was added dropwise via syringe. Once
3
4
)
11.2 Hz, NCHH), 3.67 (s, 3H, OCH
Hz, CHdCCH ), 1.46 (s, 3H, ArCCH
CDCl
3
), 2.18 (d, 3H, J ) 1.3
). C NMR (75 MHz,
(
13
3
3
2
3
): δ 153.9, 148.5, 129.1, 129.0, 128.8, 126.6, 126.2, 125.9,
16.7, 63.5, 52.5, 47.2, 35.4, 28.7, 15.9. IR (film) 2956, 2858,
0
1
1
the addition was complete, the reaction mixture was stirred
for 30 min at 0 °C. 2,2-Dimethyl-5-(trimethylsilyl)pent-4-
ynylamine (3b) (37 mg, 0.20 mmol) was then added via syringe.
The test tube was wrapped in aluminum foil and allowed to
warm to ambient temperature with stirring for 3 h. The
reaction mixture was cooled to 0 °C, and isobutyronitrile (10
mg, 0.20 mmol) was added dropwise via syringe. The rubber
septum was replaced with a plastic screw cap, and the reaction
mixture was heated at 60 °C for 4 weeks. Aqueous hydrochloric
acid (20%, 1.0 mL) was added, and the resulting mixture was
stirred an additional 4 h at 60 °C. The reaction mixture was
-1
716, 1696, 1651 cm . HRMS (EI): m/z 231. 1263 (calculated
, 231.1259).
-Ben zylid en e-4,4-d im et h ylp yr r olid in e-1-ca r b oxylic
Acid Meth yl Ester (12). Subjecting 2,2-dimethyl-5-phenyl-
-pentynylamine (3d ) (37 mg, 0.20 mmol) to the general
procedure for 11 provided the title compound as a clear oil
38 mg, 78%) after the crude material was subjected to flash
for C14
H17NO
2
2
4
(
1
chromatography (20% ethyl acetate/hexane for elution).
NMR (300 MHz, CDCl ): δ 7.29-7.18 (m, 5H, ArH), 7.11 (app
t, 1H, J ) 1.9 Ar-CHd), 3.76 (s, 3H, OCH ), 3.39 (s, 2H,
CH N), 2.58 (d, 2H, J ) 1.9 Hz CH CHd), 1.06 (s, 6H,
C(CH ): δ 154.5, 140.8, 139.1,
29.9, 128.6, 128.4, 127.5, 125.6, 110.1, 61.4, 52.8, 52.6, 45.0,
H
3
3
cooled to ambient temperature, and Et
The biphasic mixture was separated, and the aqueous phase
was extracted with Et
2
O (2.0 mL) was added.
2
2
1
3
3 2 3
) ). C NMR (75 MHz, CDCl
1
2
O (2 × 2.0 mL). The combined organic
-
1
extracts were dried over magnesium sulfate, filtered, and
concentrated in vacuo. The residue was subjected to column
chromatography (20% ethyl acetate/hexane for elution) to
provide the title compound as a slightly yellow oil (30 mg,
35.3, 26.6, 25.9. IR (film): 2948, 2871, 1722, 1713, 1645 cm
.
HRMS (EI): m/z 245.1416 (calculated for C15 , 245.1416).
H
19NO
2
Ack n ow led gm en t. Support for this research by a
grant from the National Science Foundation is grate-
fully acknowledged.
8
4%). Spectral data are identical with those of 7e.
,5-Dim et h yl-3-p h en yl-2,3-d ih yd r op yr r ole-1-ca r b ox-
3
ylic Acid Meth yl Ester (11). A flame-dried 5 mL test tube
with a Teflon-coated magnetic spinvane was charged with
TiCl
4
‚DME (2) (56 mg, 0.20 mmol) and fitted with a rubber
OM9902380