Activation of Low-Valent Titanium Reagents with Iodine: Facile Low-Temperature McMurry Reaction and N/O-Debenzylation/Deallylation

Article abstract of DOI:10.1021/jo971751v

A highly reactive, low-valent titanium (LVT) reagent has been prepared by the addition of substoichiometric amounts of iodine to the LVT species generated by Rieke's method (TiCl₃-Li-THF). While the conventional McMurry reaction requires high temperatures and prolonged reaction times for the generation of olefins, the present activated LVT reagent is able to effect the reductive coupling of aliphatic as well as aromatic carbonyls to the corresponding olefins at lower temperatures and much reduced reaction times. The protocol is also useful for the intramolecular coupling reactions leading to the one-step synthesis of heterocycles. The temperature-controlled McMurry reaction provides enhanced diastereoselectivity and features an excellent chemoselectivity. In addition to the McMurry reaction, other SET-induced carbon-heteroatom (O, N) bond cleavages can also be carried out with the activated reagent at a fast rate and at a low temperature in high yields.

Full text of DOI:10.1021/jo971751v

J . Org. Chem. 1998, 63, 4925-4929
4925
Activa tion of Low -Va len t Tita n iu m Rea gen ts w ith Iod in e: F a cile
Low -Tem p er a tu r e McMu r r y Rea ction a n d N/O-Deben zyla tion /
Dea llyla tion †
Sanjay Talukdar, Sandip K. Nayak, and Asoke Banerji*
Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai (Bombay)-400 085, India
Received September 18, 1997
A highly reactive, low-valent titanium (LVT) reagent has been prepared by the addition of
substoichiometric amounts of iodine to the LVT species generated by Rieke’s method (TiCl3-Li-
THF). While the conventional McMurry reaction requires high temperatures and prolonged reaction
times for the generation of olefins, the present activated LVT reagent is able to effect the reductive
coupling of aliphatic as well as aromatic carbonyls to the corresponding olefins at lower temperatures
and much reduced reaction times. The protocol is also useful for the intramolecular coupling reac-
tions leading to the one-step synthesis of heterocycles. The temperature-controlled McMurry reac-
tion provides enhanced diastereoselectivity and features an excellent chemoselectivity. In addition
to the McMurry reaction, other SET-induced carbon-heteroatom (O, N) bond cleavages can also
be carried out with the activated reagent at a fast rate and at a low temperature in high yields.
In tr od u ction a n d Ba ck gr ou n d
The McMurry reaction1c,5a,b finds applications in the
synthesis of strained olefins to unusual molecules such
as complex natural products including Taxol. The reac-
tion proceeds by initial electron transfer followed by
coupling to form a pinacolate which on deoxygenation
liberates the olefin. The pinacolization can be carried
out with a variety of reductants, but the deoxygenation
is unique to LVT reagents. Although titanium is known
for its high oxophilicity, the extrusion of oxygen from the
pinacolates necessitates the use of solvent-reflux tem-
peratures and prolonged reaction times. Despite the
immense potential of the McMurry reaction in synthetic
organic chemistry, the incompatibility of several func-
tionalities under the conditions of the reaction limits its
applications. Though, at lower temperatures, many of
the otherwise reducible functionalities survive, the Mc-
Murry reaction at low temperatures primarily furnishes
pinacols,5a,b,6a,b,7a-c and the olefins are obtained only at
higher temperatures and on prolonged reaction times.
This, therefore, restricts its applications in the case of
oxygenated complex natural products with semicompat-
ible functionalities, where the introduction of olefinic
double bonds is achieved by the initial pinacolization at
lower temperatures followed by deoxygenation through
indirect milder methods.5a The development of a protocol
for direct one-step olefination reaction at lower temper-
atures is therefore of prime importance and offers chal-
lenges to organic chemists.
Designing reagents for selective organic transforma-
tions is an important domain of research in synthetic
chemistry. For the transition-metal-based reagents in
general, and for low-valent titanium (LVT) in particular,
it is widely known1a-d that the reactivity, reproducibility,
and stereochemistry of reaction products vary greatly
with the source of the metal, its method of preparation,
and the experimental conditions. In a continuation of
our work on the rational design of organometallic re-
agents,1b,2a-e fine-tuning of the reactivity of LVT was
achieved by using external ligands, including π-acid spe-
cies such as pyridine, triphenylphosphine, and fullerenes.
Very recently, the ligand effects on the McMurry pinacol
reactions have been examined.3 Use of chemical redox
agents4a,b for the modulation of reactivity of organome-
tallic electron-transfer processes offers attractive pos-
sibilities for the design of novel LVT-based reagents by
controlling the redox potential of titanium complexes. The
influence of redox agents on the reactivity of LVT-based
reagents has not received much attention and is therefore
long overdue. The present investigation deals with the
modulation of the reactivity of LVT reagents using iodine
as an external redox agent. The activated reagent
performs McMurry’s carbonyl coupling and other SET-
induced reactions at lower temperatures and in improved
yields.
† In respectful memory of the late Professor Sir Derek H. R. Barton.
(1) (a) Dams, R.; Malinowski, M.; Westdorp, I.; Geise, Y. H. J . Org.
Chem. 1982, 47, 248. (b) Nayak, S. K.; Banerji, A. J . Org. Chem. 1991,
56, 1940. (c) Dushin, R. G. In Comprehensive Organometallic Chemistry
II; Hegedus, L. S., Ed.; Pergamon: Oxford, 1995; Vol. 12, p 1071 and
references therein. (d) Szymoniak, J .; Besancon, J .; Mo¨ıse, C. Tetra-
hedron 1992, 48, 3867.
(2) (a) Banerji, A.; Nayak, S. K. J . Chem. Soc., Chem. Commun.
1990, 150. (b) Nayak, S. K.; Kadam, S. M.; Talukdar, S.; Banerji, A. J .
Indian Inst. Sci. 1994, 74, 401. (c) Talukdar, S.; Nayak, S. K.; Banerji,
A. Full. Sci. Technol. 1995, 3, 327. (d) Balu, N.; Nayak, S. K.; Banerji,
A. J . Am. Chem. Soc. 1996, 118, 5932 and references therein. (e)
Talukdar, S. Ph.D. Thesis, 1997, University of Mumbai, Mumbai, India.
(3) Lipski, T. A.; Hilfiker, M. A.; Nelson, S. G. J . Org. Chem. 1997,
62, 4566.
For the synthesis of olefins at lower temperatures, the
activation of LVT species becomes imperative. Reactive
LVT reagents have been prepared using Rieke’s protocol8a,b
involving reduction of titanium halides with an alkali
metal (lithium, sodium, or potassium) in an ethereal or
hydrocarbon solvent. However, the reactive metals have
the intrinsic tendency toward deactivation and, therefore,
require further depassivation or secondary activation.
Several reagents such as iodine, methyl iodide, ethyl
(5) (a) McMurry, J . E. Chem. Rev. 1989, 89, 1513. (b) Fu¨rstner, A.;
Bogdanovic, B. Angew. Chem., Int. Ed. Engl. 1996, 35, 2442 and
references therein.
(6) (a) McMurry, J . E.; Rico, J . G. Tetrahedron Lett. 1989, 30, 1169.
(b) McMurry, J . E.; Dushin, R. G. J . Am. Chem. Soc. 1990, 112, 6942.
(4) (a) Connelly, N. G.; Geiger, W. E. Chem. Rev. 1996, 96, 877 and
references therein. (b) Hirao, T. Chem. Rev. 1997, 97, 2707 and
references therein.
S0022-3263(97)01751-9 CCC: $15.00 © 1998 American Chemical Society
Published on Web 07/07/1998

4926 J . Org. Chem., Vol. 63, No. 15, 1998
Talukdar et al.
Ta ble 1. Com p a r a tive Rea ctivity of Va r iou s Low -Va len t Tita n iu m Rea gen ts w ith Acetop h en on e (1a )
time (h),
temp (°C)
% yielda (dl:meso)b,c
of 2a
% yielda
of 3a
entry
LVT reagent
additive (equiv)
1
2
3
4
5
6
7
8
TiCl3-Li-THF
TiCl3-Li-THF
TiCl3-Li-THF
TiCl3-Li-THF
TiCl3-Li-THF
TiCl3-Mg-THF
TiCl3-Li-THF
TiCl3-Li-THF
Nil
Nil
I2 (0.25)
I2 (0.25)
I2 (0.125)
I2 (0.25)
ethyl bromide (0.25)
1,2-dibromoethane (0.25)
16, reflux
16, 0-5
2, 0-5
nil
87 (75:25)
nil
trace
nil
nil
89
trace
90
2, -40
75
3.5, 0-5
18, 0-5
5, 0-5
87
80d
25
67 (80:20)
nil
5, 0-5
87
a
All yields refer to isolated products (purity > 95%, analyzed by 1H NMR). The products were fully characterized by comparison (TLC,
mp, 1H NMR, IR) with authentic samples.2d,11 Ratios determined by 1H NMR analysis of crude product mixtures. c Stereochemical
b
assignments are made by comparison of spectroscopic data to that reported in the literature.2d The stereoisomeric composition of stilbene
d
mixture 3a is presented in Table 3. Considering 15% of recovered substrate 1a .
Sch em e 1
using as low as 0.125 equiv of iodine, but with increased
reaction time (Table 1, entry 5). Iodine is also effective
in activating the Tyrlik’s LVT reagent1c (TiCl3-Mg-
THF), although its effect was comparatively less pro-
nounced. Thus, using TiCl3-Mg-THF-I2 (0.25 equiv)
reagent, 3a was obtained in 80% yield after 18 h at 0-5
°C (Table 1, entry 6). Among the reactive alkyl halides,
ethyl bromide and 1,2-dibromoethane were tried for the
activation study. Using ethyl bromide, the carbonyl-
olefin transformation resulted in a low yield (25%) of
stilbene 3a at 0-5 °C (Table 1, entry 7) (the major
product was 2a ). In contrast, using 1,2-dibromoethane,
3a (87%) was obtained after 5 h reaction (Table 1, entry
8). The diol 2a was obtained as a diastereomeric (dl:
meso) mixture (Table 1, entries 2 and 7), and their
stereoisomeric composition has been assigned by com-
parison with the literature data.2d The profile of the
McMurry reaction using various additives as activators
for LVT reagents establishes that TiCl3-Li-THF-I2
(0.25 equiv) (LVT-I2, reagent B) is the best combination
and, therefore, was used for further studies.
bromide, and especially 1,2-dibromoethane have been
reported for the activation8a,b of metals. Recent reports8a,b
on the effects of iodine on transition-metal-mediated
transformations prompted us to investigate its effect on
LVT reagents. Although iodine did not activate the
commercial titanium powder,7c herein, an efficient strat-
egy for the preparation of a highly reactive LVT reagent
by the addition of substoichiometric amounts of iodine
to the Rieke’s LVT (TiCl3-Li-THF) species is presented.
Resu lts a n d Discu ssion
Gen er a lity a n d Ch em oselectivity. To explore the
generality and scope of reagent B, experiments were
carried out using a variety of aryl carbonyls, such as aryl
alkyl ketones (Table 1, entry 3; Table 2, entries 1, 2, and
7), diaryl ketone (Table 2, entry 3), and aryl aldehydes
(Table 2, entries 4-6) (Scheme 1). The reaction is also
applicable to the less reactive aliphatic carbonyls. Thus,
the aliphatic aldehydes (Table 2, entries 8 and 9), as well
as aliphatic ketones (Table 2, entries 10-12), undergo
facile coupling to olefins at 25 °C. The scope of the low-
temperature McMurry reaction for the synthesis of
heterocycles,1c,5b,8b via the intramolecular keto ester
coupling of o-aroyloxyacetophenones developed earlier in
our laboratory,2a was also explored. Thus, both 2-(ben-
zoyloxy)acetophenone (4a ) and 2-(benzoyloxy)-5-meth-
oxyacetophenone (4b) on reaction with reagent B gener-
ated the corresponding benzofurans 5a (62%) and 5b
(55%), respectively (eq 1), at 25 °C. The low-temperature
P r ep a r a tion of Activa ted LVT Rea gen t a n d Mc-
Mu r r y Rea ction . Coupling of acetophenone (R1 ) Ph,
R2 ) CH3; 1a ) to the corresponding stilbene, viz. 2,3-
diphenyl-2-butene (3a ), was chosen as a model reaction
(Table 1, Scheme 1). The LVT was prepared in situ as a
black slurry by reducing TiCl3 with Li in THF (TiCl3-
Li-THF, reagent A). On addition of iodine (0.25 equiv),
formation of a brown soluble species was observed. When
1a (0.25 equiv to TiCl3) was added to the modified TiCl3-
Li-THF-I2 (reagent B), 3a was obtained in 90% yield
at 0-5 °C within 2 h without a trace of the intermediate
pinacol, 2,3-diphenylbutane-2,3-diol (2a ) (Table 1, entry
3). In contrast, in the absence of iodine, the pinacol 2a
was isolated in 87% yield even when the reaction was
carried out for 16 h (Table 1, entry 2). Under McMurry’s
conditions,9 prolonged (16 h) reflux was required to obtain
stilbene 3a (89%, Table 1, entry 1). Using iodine (reagent
B), 3a was isolated as the major product (Table 1, entry
4), even at -40 °C. This clearly shows the dramatic role
of iodine in augmenting the reactivity of LVT reagents.
The reaction could also be carried out in comparable yield
(7) (a) Fu¨rstner, A.; Weidmann, H. Synthesis 1987, 1071. (b)
Fu¨rstner, A.; Csuk, R.; Rohrer, C.; Weidmann, H. J . Chem. Soc., Perkin
Trans. 1 1988, 1729. (c) Fu¨rstner, A.; Hupperts, A. J . Am. Chem. Soc.
1995, 117, 4468.
(8) (a) Cintas, P. Activated Metals in Organic Synthesis; CRC
Press: Boca Raton, 1993. (b) Fu¨rstner, A. Active Metals-Preparation,
Characterization, Applications; VCH: Weinheim, 1996 and references
therein.
(9) McMurry, J . E.; Fleming, M. P.; Kees, K. L.; Krepski, L. R. J .
Org. Chem. 1978, 43, 3255.
reaction induced by iodine is also useful in performing
the carbonyl coupling reaction chemoselectively in the
presence of reducible functionalities, viz. aryl-OMe and
alkyl and aryl halides which are otherwise incompatible

Activation of Low-Valent Titanium Reagents
J . Org. Chem., Vol. 63, No. 15, 1998 4927
Ta ble 2. Red u ctive Cou p lin g of Ca r bon yls (1) to Olefin s (3) a t Low Tem p er a tu r e Usin g TiCl3-Li-THF -I2
time (h),
temp (°C)
% yielda
entry
R1
R2
CH3
CH3
Ph
H
H
H
compd
(E/Z)b of 3
ref
1
2
3
4
5
6
7
8
9
2-naphthyl
2-naphthyl
1b, 3b
1b, 3b
1c, 3c
1d , 3d
1e, 3e
1f, 3f
1g, 3g
1h , 3h
1i, 3i
8, 25
6, 0-5
5, 25
3, 0-5
2.5, 0-5
3.5, 0-5
5, 0-5
8, 25
4, 25
5, 25
6, 25
8, 25
69 (48/52)
93 (64/36)
95
2d
2d
9
7c
2d
1d
2e
7b
2e
9
Ph
Ph
85 (only E)
4-Cl-C6H4
4-MeO-C6H4
82 (only E)
62c (only E)
Ph
(CH2)2Cl
69d
80
79
88
71
59
n-C7H15
PhCH2
H
H
e
10
11
12
e
f
i-Pr
1j, 3j
1k , 3k
1l, 3l
f
9
9
i-Pr
a
b
All yields refer to isolated products (purity > 95%, analyzed by 1H NMR); fully characterized by IR and 1H NMR. Ratios determined
by 1H NMR analysis of crude product mixtures as reported1d,2d,7c,11 in the literature. c11% of 2d was also formed. 6% of 3,4-diphenylhex-
d
3-ene was also isolated. e R1, R2 corresponds to cyclohexanone. f R1, R2 corresponds to cyclopentanone.
under reflux conditions10a-c (Table 2, entries 5-7). Thus,
the addition of I2 not only accelerates McMurry’s olefi-
Ta ble 3. Low -Tem p er a tu r e McMu r r y Rea ction : Effect
on Ster eoselectivity
time (h),
stilbene
E/Z
nation at lower temperatures but also offers excellent
chemoselectivity.
entry substrate reagentsa temp (°C) (% yield) ratio11
The isomeric ratio (E/Z) of the diastereomeric olefins
3a , 3b, and 3d -f were determined on the basis of H
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1b
1b
1b
A
B
B
B
B
A
B
B
16, reflux
2, reflux
2, 25
2, 0-5
2, -40
16, reflux
8, 25
3a (89)
3a (80)
3a (92)
3a (90)
3a (75)
3b (74)
3b (69)
3b (93)
75:25
52:48
74:26
80:20
92:8
37:63
48:52
64:36
1
NMR spectroscopic data as is reported1d,2d,7c,11 in the
literature. The stereochemical assignment of the tetra-
substituted 2,3-biaryl olefin, i.e., 2,3-bis(2′-naphthyl)-2-
butene (3b), obtained from 2-naphthyl methyl ketone
(1b), was made by comparing the resonances of the allylic
methyl protons for the Z (downfield signals) and E
(upfield signals) isomers similar to the configurational
assignments of 2,3-diphenyl-2-butene (3a ) by Anders-
son.11 A chromatographically pure diastereoisomeric
mixture was used for the analysis.
6, 0-5
a
A ) TiCl3-Li-THF, B ) TiCl3-Li-THF-I2
reactions invented in our laboratory was also investi-
gated. Thus, in a new approach to deprotection of alco-
hols/phenols, efficient protocols for LVT-mediated O-allyl/
benzyl/propargyl bond cleavages were reported.12a,b Al-
though, O-benzyl/allyl ethers undergo cleavage readily,
the reactions with N-allyl/benzylamines10b are compara-
tively slow and require prolonged reflux (∼22 h). In
addition, the yields of N-allyl/benzyl bond cleavages are
lower compared to their oxygen counterparts. It was
therefore anticipated that the use of the activated LVT-
I2 system would enhance the yields of the reactions.
Hence, a systematic study of the effect of LVT-I2 system
on otherwise sluggish and low-yielding O/N-debenzyla-
tions/deallylations was also carried out.
In a model reaction, when N-allyl-N-benzylaniline (6a )
was subjected to the LVT-I2 system (Scheme 2), the
regioselective deallylation to N-benzylaniline (6b) at 25
°C required 16 h (76%, Table 4, entry 2). However, the
yield of 6b dropped down to 49% when the reaction was
repeated in absence of iodine (reagent A) and required
reflux temperature (Table 4, entry 1).
Gen er a lity a n d Utility. To explore the scope of the
protocol, reactions were performed using a variety of N/O-
benzyl/allyl substrates (Scheme 2). The cleavage of
O-allyl bond in 4-(2-propenyloxy)biphenyl (7a ) is facili-
tated when iodine-activated LVT species is used. Even
at -10 °C, the deprotected 4-phenylphenol (7b) was
obtained in a yield of 83% in only 1 h, while without I2
7b was produced at reflux temperature (72%, 3 h) (Table
4, entries 3 and 4). The iodine-promoted mild protocol
for the N/O-debenzylations has also been successfully
employed for the removal of the benzyl moiety used for
Effect on Dia ster eoselectivity. The stereoselectiv-
ity during olefination is a function of the number of
interdependent variables,1a-c such as solvent, the nature
of the active reagent (valences etc.), external auxiliaries,2d
temperature, and steric bulk of the groups. Stereoselec-
tivity is therefore, amenable to tuning by judicious
designing of reagents and reaction conditions.1b In the
present investigation it has been observed that the
olefination at lower temperatures is attended with en-
hanced diastereoselectivity as compared to those obtained
under higher temperatures and on prolonged reaction
times. Thus, the reaction of acetophenone (1a ) with
reagent A required reflux conditions and generated the
E isomer11 of 2,3-diphenyl-2-butene (3a ) (75%, Table 3,
entry 1). However, using reagent B with the low-tem-
perature pathway, E selectivity in 3a could be aug-
mented. Reactions at 0-5 °C and -40 °C were attended
with 80% and 92% of E selectivity, respectively (Table 3,
entries 4 and 5), offering enhanced diastereoselectivity.
In the case of 2-naphthyl methyl ketone (1b), reaction
with reagent A was attended with the preferential for-
mation of the Z isomer (63%) of 2,3-bis(2′-naphthyl)-2-
butene (3b) (Table 3, entry 6). However, in the presence
of iodine (reagent B) complete reversal of the stereose-
lectivity in 3b was observed on going down gradually to
0-5 °C (Table 3, entries 7 and 8).
O/N-Deben zyla tion s/Dea llyla tion s w ith Rea gen t
B. The scope of the reagent B for other SET-induced
(10) (a) Tyrlik, S.; Wolochowicz, I. J . Chem. Soc., Chem. Commun.
1975, 781. (b) Talukdar, S.; Banerji, A. Synth. Commun. 1995, 25, 813.
(c) Talukdar, S.; Banerji, A. Synth. Commun. 1996, 26, 1051.
(11) Isomeric ratio of 3a are established using spectroscopic data,
see: Andersson, P. G. Tetrahedron Lett. 1994, 35, 2609.
(12) (a) Kadam, S. M.; Nayak, S. K.; Banerji, A. Tetrahedron Lett.
1992, 33, 5129. (b) Nayak, S. K.; Kadam, S. M.; Banerji, A. Synlett.
1993, 581.

4928 J . Org. Chem., Vol. 63, No. 15, 1998
Talukdar et al.
Sch em e 2
yield of 52% indole (9b) (Table 4, entry 8) at reflux
temperature. Likewise, when N-benzyl skatole (10a ) was
subjected to reagent B, smooth deprotection produced
skatole (10b) at 25 °C (75%) (Table 4, entry 9). Similarly,
N-benzylcarbazole (11a ) underwent ready cleavage of the
benzyl moiety triggered by the LVT-I2 reagent (Table
4, entry 10). Thus, the present protocol enhances the
scope of the benzyl group for the N-protection of indoles.
Mechanistically, LVT species, generated in situ by the
reduction of TiCl3 with Li, is a suspension of titanium
mostly in the zero valence state.1a The significant role
of chemical redox agents in influencing the electron-
transfer reactions resulting in the chemical activation of
organometallic complexes was comprehended in recent
times.4a,b It is proposed that, in the present case, the
addition of iodine to the Rieke’s LVT reagent drives the
reaction toward the formation of TiI2 species, demanded
by the respective redox potential16 values (eq 2). TiI2, in
turn, disproportionates to a very reactive TiI species (eq
3), resulting in an increase in nascent, active reagents
(probably the TiI2-Ti system). This postulation is simi-
lar to the one for the activation of magnesium by iodine.17
Ta ble 4. Clea va ge of N/O-Allyl/Ben zyl Bon d s Usin g
TiCl3-Li-THF -I2 Rea gen t
I2 + Ti(0) h 2I- + Ti2+ f TiI2
TiI2 + Ti h 2TiI
(2)
(3)
time (h),
temp (°C)
product
entry
substrate
reagentsa
(% yieldb)
ref
1
2
3
4
5
6
7
8
9
6a
6a
7a
7a
8a
8a
9a
9a
10a
11a
A
B
A
B
A
B
B
A
B
B
18, reflux
16, 25
3, reflux
1, -10
12, reflux
5.5, 25
16, 25
16, reflux
16, 25
6b (49)
6b (76)
7b (72)
7b (83)
8b (60)
8b (79)
9b (85)
9b (52)
10b (75)
11b (80)
10b
10b
12b
12b
13
13
2e
2e
2e
Con clu sion s
An efficient protocol for the generation of highly
reactive LVT reagent by using substoichiometric amounts
of iodine has been developed. Compared to Rieke’s
activated LVT (TiCl3-Li-THF) species, the present
highly reactive LVT-I2 (0.25 equiv) reagent displays
unique reactivity wherein olefins can be generated di-
rectly from the carbonyls at 0 °C or even lower temper-
atures and at a faster rate as compared to the conven-
tional high-temperature couplings. It features an en-
hanced chemo- and diastereoselectivity. The present
reagent also performs the intramolecular keto ester
coupling under milder conditions. In addition, SET-
induced cleavage of O/N-allyl/benzyl bonds is influenced
by the activated reagent. An expedient method for the
debenzylation of indoles and alcohols/phenols or amines
has been formulated. The present investigation high-
lights the involvement of chemical redox agents in the
organometallic electron transfer processes. This protocol
is likely to find wider applications in preparative organic
chemistry. It presents a unique conceptual advance
which further defines its scope and applicability in
classical McMurry reaction, particularly in the domain
of oxygenated natural products. Insights enumerated
herein open the doors on a variety of fronts for further
endeavors using organometallic reagents and will en-
courage the use of redox agents for fine-tuning of their
reactivities under redox potential control. Further stud-
ies in this direction for the preparation of novel LVT-
based reagents using metal arenes as potential reduc-
tants for titanium halides are presently under in-
vestigation in this laboratory.
10
16, 25
15b
As is described in Table 3. b All yields refer to isolated products
(purity > 95%, analyzed by 1H NMR); fully characterized by IR
and 1H NMR.
a
the protection13 of the hydroxyl group in cholesterol.
Debenzylation of 3-(phenylmethoxy)cholest-5-ene (8a )
using reagent A gave cholesterol (8b) in a yield of 60%
after 12 h at reflux (Table 4, entry 5). However, using
reagent B, the yield of the transformation increased to
79%, requiring only 5.5 h at 25 °C (Table 4, entry 6).
The improved method for the deprotection of alcohols
and amines has been extended to indole and its deriva-
tives. Protection of the indole nitrogen plays an impor-
tant role in synthetic indole chemistry, including syn-
thesis of indole natural products.14 Although the benzyl
group is the most useful protecting group for indolic
nitrogen, only limited methods are available for their
deprotection.15a,b However, using LVT-I2 reagent, N-
debenzylation of a variety of indoles could be easily
performed under milder conditions with high yields.
Thus, the N-benzyl indole (9a ) could be cleaved readily
at 25 °C with 85% conversion (Table 4, entry 7). How-
ever, in the absence of I2, debenzylation results in only a
(13) Akiyama, T.; Hirofuji, H.; Ozaki, S. Tetrahedron Lett. 1991, 32,
1321.
(14) Ketcha, D. M.; Lieurance, B. A.; Homan, D. F. J . J . Org. Chem.
1989, 54, 4350.
(15) (a) Green, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis; 2nd ed.; J ohn Wiley & Sons: New York, 1991. (b) Sujuki,
H.; Tsukuda, A.; Konda, M.; Aizawa, M.; Senoo, Y.; Nakajima, M.;
Watanabe, T.; Yokoyama, Y.; Murakami, Y. Tetrahedron Lett. 1995,
36, 1671.
(16) Standard reduction potentials (E°) of Ti2+/Ti and I2/2I- systems
are -1.63 V and +0.54 V respectively, see: Braun, R. D. Introduction
to Instrumental Analysis; McGraw-Hill International Edition: New
York, 1987; p 700.
(17) Lai, Y.-H. Synthesis 1981, 585.

Activation of Low-Valent Titanium Reagents
J . Org. Chem., Vol. 63, No. 15, 1998 4929
amines (2.5 mmol, 5 mL of THF). The reaction mixture was
then stirred at different temperatures as indicated in Tables
1-4 for respective substrates. After completion (TLC), it was
diluted with hexane and passed through Celite. Extraction
with an ethyl acetate-hexane (20:80) mixture, followed by
washing with brine and drying over Na2SO4, yielded the crude
product which was purified by preparative TLC (SiO2, hexane)
to furnish olefins or the deprotected phenols/alcohols or
amines.
All the products are known compounds and were character-
ized by comparison (mp, 1H NMR, IR) with the literature data
(references are presented in the Tables 1-4) for authentic
samples.
Exp er im en ta l Section
Gen er a l Meth od s. General information regarding instru-
ments, techniques, and source of chemicals used is the same
as mentioned in our previous publication.2d Lithium rods cut
into small pieces were used for the reduction of titanium
chlorides.
Gen er a l P r oced u r e for Iod in e-P r om oted LVT-In d u ced
Ca r bon yl Cou p lin gs a n d N/O-Deben zyla tion s/Dea llyla -
tion s. A mixture of TiCl3 (1.55 g, 10 mmol) and Li (0.231 g,
33 mmol) in dry THF (50 mL) was refluxed (3 h, argon). After
cooling, iodine crystals (0.635 g, 2.5 mmol) were added in
portions and the mixture was stirred (5 min). On addition of
iodine, the black suspension of LVT gradually turned brown.
To the activated LVT-I2 reagent, thus prepared, was added a
carbonyl compound or O/N-allyl/benzyl derivative of ethers or
J O971751V