Vanadium(I) chloride and lithium vanadium(I) dihydride as selective epimetallating reagents for π- and σ-bonded organic substrates

Article abstract of DOI:10.1002/ejoc.200800461

Subvalent vanadium(I) salts, of empirical formulas, VCl, vanadium(I) chloride and LiVH₂, lithium vanadium(I) dihydride, whose efficient preparation, structural constitution and mode of reaction toward certain organic substrates have been described in a preceding article, are here evaluated in their reactions toward a wide variety of π- and σ-bonded organic substrates, namely carbonyl, imine, azo, alkene, 1,3-diene, nitrile π-bonds and C-X, C-O, C-N and N-N σ-bonds. Compared with the high reactivity of CrCl and LiCrH₂ reagents in attacking both types of bonds, the VCl and LiVH₂ reagents were much milder and selective in epimetallating π-bonds, often forming the 1:1 adduct of LiVH₂ and π-bonded substrate as the major product. Finally, the vanadium reagents showed little tendency to cleave C-O, C-S and C-N bonds and a smaller scope in cleaving C-X bonds than their chromium counterparts. Because of their selectivity these vanadium reagents offer the following preparative promise: 1) smooth McMurry carbonyl coupling to their reductive dimers; 2) deoxygenation of epoxides; 3) selective aromatic C-X reduction; 4) high yields of epimetallated carbonyls or imines as intermediates to α-hydroxy and α-amino acids; 5) 1,4-reductions of 1,3-alkadienes; 6) reductive dimerization of nitriles to ketones; 7) 1,4 or 1,n-epimetallations leading to acyloins or indoles; and 8) reductive dimerizations of azines to produce unusual imidazole derivatives. In explaining the greater kinetic stability of the 1:1 LiVH₂ adduct with carbonyl or imine substrates it is pointed out that such epimetallated adducts from LiVH₂ would likely be diamagnetic, whereas such adducts from LiCrH₂ have an unpaired electron on the Cr center and hence would rupture, so that the electron would be on the C center. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.

Full text of DOI:10.1002/ejoc.200800461

FULL PAPER
DOI: 10.1002/ejoc.200800461
Vanadium(I) Chloride and Lithium Vanadium(I) Dihydride as Selective
Epimetallating Reagents for π- and σ-Bonded Organic Substrates[‡]
John J. Eisch*[a] and Paul O. Fregene[a]
Dedicated to Professor Dr. Udo H. Brinker on the occasion of his 65th birthday
Keywords: Vanadium(I) chloride / Lithium vanadium(I) dihydride / Epimetallation / Cleavage of carbon-heteroatom
bonds / Reductive dimerization
Subvalent vanadium(I) salts, of empirical formulas, VCl, va-
nadium(I) chloride and LiVH2, lithium vanadium(I) dihy-
dride, whose efficient preparation, structural constitution and
mode of reaction toward certain organic substrates have
been described in a preceding article, are here evaluated in
their reactions toward a wide variety of π- and σ-bonded or-
ganic substrates, namely carbonyl, imine, azo, alkene, 1,3-
diene, nitrile π-bonds and C–X, C–O, C–N and N–N σ-bonds.
Compared with the high reactivity of CrCl and LiCrH2 rea-
gents in attacking both types of bonds, the VCl and LiVH2
reagents were much milder and selective in epimetallating
π-bonds, often forming the 1:1 adduct of LiVH2 and π-bonded
substrate as the major product. Finally, the vanadium rea-
gents showed little tendency to cleave C–O, C–S and C–N
bonds and a smaller scope in cleaving C–X bonds than their
chromium counterparts. Because of their selectivity these va-
nadium reagents offer the following preparative promise: 1)
smooth McMurry carbonyl coupling to their reductive di-
mers; 2) deoxygenation of epoxides; 3) selective aromatic C–
X reduction; 4) high yields of epimetallated carbonyls or im-
ines as intermediates to α-hydroxy and α-amino acids; 5) 1,4-
reductions of 1,3-alkadienes; 6) reductive dimerization of ni-
triles to ketones; 7) 1,4 or 1,n-epimetallations leading to acy-
loins or indoles; and 8) reductive dimerizations of azines to
produce unusual imidazole derivatives. In explaining the
greater kinetic stability of the 1:1 LiVH2 adduct with car-
bonyl or imine substrates it is pointed out that such epimetal-
lated adducts from LiVH2 would likely be diamagnetic,
whereas such adducts from LiCrH2 have an unpaired elec-
tron on the Cr center and hence would rupture, so that the
electron would be on the C center.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
mechanisms of Ziegler–Natta processes.[3] As a fertile off-
shoot of that investigation, such studies have led to the syn-
thesis of many subvalent transition metal complexes and a
fundamental examination of their reactions with unsatu-
rated organic substrates. The principal and pioneering effort
in this field, launched independently in 1973 by the research
groups of Mukaiyama, of Tyrlik and of McMurry, involved
subvalent titanium reagents of uncertain oxidation state
and their efficiency in reductively dimerizing ketones into
olefins.[4] Following their lead, many researchers began to
explore the reducing action of subvalent transition metal
reagents encompassing divalent complexes of titanium,
chromium and vanadium for organic transformations. The
copious literature on such research has been meticulously
reviewed.[5] In these studies the actual oxidation state of the
transition metal remained uncertain, as with Ti, or was no
lower than divalent, as with Cr and V.
Introduction
Transition metals, especially in the colloidal state, have
proved to be outstanding hydrogenation catalysts for over
a century. Then just over 50 years ago, the revolutionary
researches of Karl Ziegler and of Guilio Natta have shown
that subvalent transition metal salts, when combined with
main group metal alkyls, can serve as potent and stereose-
lective oligomerization and polymerization catalysts for a
wide range of unsaturated hydrocarbons.[2] The swift world-
wide impact of their research is reflected in the mere ten
years extending from their initial publications of success to
the awarding of their joint Nobel Prize in 1963. In the ensu-
ing 35 years it has become the chief endeavor of industrial
and academic chemists alike to elucidate the molecular
[‡] Organic Chemistry of Subvalent Transition Metal Complexes,
44. Part 43: Ref.[1]
About 15 years ago we recognized the need to find a
general methodology able to generate such transition reduc-
tants in defined low oxidation state efficiently and with a
minimum of main-group metal reductant or Lewis acid as
[a] State University of New York at Binghamton, Department of
Chemistry,
P.O. Box 6000, Binghamton, NY 13902-6000, U.S.A
Fax: +1-607-777-4865
E-mail: jjeisch@binghamton.edu
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Selective Epimetallating Vanadium(I) Reagents
impurities. This requisite process has proved to be alkylative
reduction.[6] Illustrated in Equation (1) for TiCl2 (3),[7] it
appears to be generally applicable to early transition metal
(4)
[9]
salts, such as Ti(i-OPr)2,[8] ZrCl2,[9] Zr(OEt)2,[10] HfCl2
and CrCl.[11] The reaction occurs by the partial alkylation
of TiCl4 (1) in THF at –78 °C by n-butyllithium and the
subsequent loss of butyl radicals from 2 above 0 °C.
Purpose of the Present Study
Of all of the foregoing subvalent transition-metal com-
plexes prepared by our group thus far, the two most active
reagents for epimetallating π-bonded substrates and for
cleaving σ-carbon–heteroatom (O, N, S, X) bonds have
been found to be chromium(I) chloride (10)[11] and lithium
chromium(I) dihydride (6).[12] Illustrative of the wide scope
of high-yielding reactions achievable with CrCl (10) are
those given in Scheme 1.[11] But lithium chromium(I) dihy-
dride (6) was thereafter shown to surpass in reactivity any
neutral subvalent transition metal complex yet prepared by
us, including CrCl. Reagent 6 can for example: 1) cleave the
σ-C–O bond or C–S bond in dibenzofuran or in dibenzo-
thiophene, respectively; 2) cleave the σ-C–N bond in benzyl-
amine and deaminate the compound completely; 3) initiate
polymerization of styrene or methyl methacrylate; and 4)
dehalogenate aromatic halides, all reactions indicative of
the extraordinary reducing action of 6.[12]
(1)
In an important modification, the interaction of the ini-
tial CrCl3 (4) or TiCl4 (1) salt with four or five equivalents
of n-butyllithium, respectively, appears to form a lithium
alkylmetallate (5) in Equation (2), whose reductive dealky-
lation leads to the lithium metal hydride, LiCrH2 (6).[12] The
corresponding reactions starting with TiCl4 would produce
LiTiH3, but this hydride has been found to be stable only
below 0 °C.[13]
(2)
Such resulting subvalent transition-metal complexes,
MtmEn (7), can add, in varying individual scope, to a range
of π-bonded systems (C=C, CϵC, C=O, C=N and CϵN
bonds) to form adducts. Such an adduct with an alkyne (8),
for example, can be considered, on the one extreme, as a
simple π complex (9a), where there is relatively little net
electron density transferred from the metal (oxidation no.
m, with increase ≈ 0) [Equation (3)]. In another resonance
contribution, however, much electron transfer from the
metal may lead to the bonding in 9b, which resembles that
of a metallocycle (oxidation no. m increase approaching 2).
Scheme 1.
(3)
This great reactivity of these two chromium reagents in
the epimetallation of π- and σ-bonds of carbon roused our
Whether one of these two resonance forms is the better interest in the corresponding reagents of vanadium, VCl
approximation of 9 can only be decided by assessing the (11) and LiVH2 (12). In the preceding publication in this
structural and chemical properties of individual com- series[1] we have described the preparation and structural
plexes.[14] If, for example, the bond length in 9 approximates characterization of these vanadium reagents. The signifi-
that of a C=C bond in a cyclopropene and if in reactions cance of these transition metal complexes lies in their being
of 9, insertions or cleavages, seem to be occurring at two the first chromium or vanadium reductants shown to exist
separate C–M bonds, then structure 9b is a more reliable in a univalent oxidation state. Although VCl gives no clear
structural representation. The term proposed for the ad- indication of being paramagnetic, LiVH2 exhibits an EPR
dition of the metal complex MtmEn onto a π-bond to form spectrum consistent with the presence of an anion having a
a metallocycle like 9b is epimetallation.[14]
linear H–V–H structure and two unpaired electrons. Both
In an analogous reaction of a generalized subvalent tran- reagents have been shown to undergo epimetallations in-
sition metal complex, MtmEn, with a σ C–EЈ bond (EЈ = C, volving radical intermediates.
O, N, X), leading to cleavage [Equation (4)], such a reaction
With this insight into the compositions and modes of
reaction of VCl (11) and LiVH2 (12), we have now under-
may also be viewed as an epimetallation.[14]
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J. J. Eisch, P. O. Fregene
FULL PAPER
taken a survey of their reductions of selected organic sub-
strates. The goal of this study has been to learn what differ-
ences would exist between the reactivity of these vanadium
reagents and their chromium counterparts, where the metal
nuclei differ by only one proton, V with the atomic number
of 23 and Cr with that of 24. As to their lithium metal
Results and Discussion
Reductions of Organic Substrates with Vanadium(I)
Chloride (11)
A variety of typical organic π- and σ-bonded functional
dihydrides, we now could compare the chemical reactivity groups was allowed to react with a THF solution of two
of the free radical LiCrH2 with that of the biradical LiVH2. equiv. of VCl (11) at 25 °C for 12 h (Table 1). All the sub-
Table 1. Reductions of π- and σ-bonded organic substrates with vanadium(I) chloride (VCl, 10).
Entry
1
Substrate[a]
Product(s)
Yield[b]
benzaldehyde
benzyl alcohol
1,2-diphenyl-1,2-ethanediol (2:1, rac/meso)
1-phenylethanol
2,3-diphenyl-2,3-butanediol (1.2:1.0, rac/meso)
diphenylmethanol
1,1,2,2-tetraphenyl-1,2-ethanediol
9,9Ј-bifluorenyl-9,9Ј-diol
9,9Ј-bifluorenylidene
9,9Ј-bifluorenyl
20
63
45
55
51
33
43
32
16
5
2
3
4
acetophenone
benzophenone
9-fluorenone[c]
9-fluorenol
fluorene
4
5
6
9-fluorenone[d]
N-benzylidenemethylamine
9,9Ј-bifluorenylidene
benzyl(methyl)amine
1,2-bis(methylamino)-1,2-diphenylethane (1.0:2.3, rac/meso)
benzyl phenyl ketone
butyl phenyl ketone
pentanoic acid
aniline
hydrazobenzene
stilbene (E/Z = 97:3)
acenaphthene
polystyrene (atactic)
1,1-diphenylethane
99
48
52
3
7
benzonitrile
10
17
75
25
100
62
100
30
100
64
10
26
39
22
8
24
76
77
23
92
1
8
9
carbon dioxide
azobenzene
10
11
12
13
14
15
E-stilbene oxide
acenaphthylene
styrene
1,1-diphenylethene
Z-stilbene
stilbene (E/Z = 97:3)
(E)-1-phenyl-1-butene
(E)-1-phenyl-2-butene
1-phenylbutane
4-phenyl-1-butene
16
(E,E)-1,4-diphenyl-1,3-butadiene (E)-1,4-diphenyl-1-butene
1,4-diphenyl-2-butene (E/Z = 1:1)
17
18
diphenylacetylene
benzyl chloride
1,2-diphenylethene (E/Z = 1:1)
toluene
1,2-diphenylethane
benzyl chloride
meso-1,2-dichloro-1,2-diphenylethane
tetraphenylethene
diphenylmethane
fluorene
19
20
21
22
benzal chloride
dichloro(diphenyl)methane
9-bromofluorene
iodobenzene
35
65
8
9,9Ј-bifluorenyl
biphenyl
benzene
anisole
4,4-dimethylbibenzyl
toluene
8
43
3
23
24
4-iodoanisole
4-bromotoluene
5
25
2-bromobiphenyl
biphenyl
100
[a] Unless otherwise noted, a typical reaction run involved 1.5–3.0 mmol of organic substrate and two molar equivs. of VCl (10) in 30 mL
of anhydrous, deoxygenated THF, which mixture was allowed to stir for 12 h at 25Ϯ5 °C before being hydrolyzed by H2O or aqueous 1
 HCl. After extraction of products into ether, the dried organic extract was evaporated, the residue weighed and the product(s) analyzed
directly by 1H and 13C NMR spectroscopy. In necessary situations, racemic- and meso-isomers were separated by column chromatography
and their relative amounts assessed by methine CH integrations in the 4.0–5.0 ppm 1H region (diols) or the 3.5–4.1 ppm region (dianilines).
[b] The difference between the total percentage of product(s) and 100% represents the percentage of remaining starting material. [c] In
this run workup of a reaction sample taken after 30 min with CO2 and hydrolysis led to about 10% yield of 9-hydroxy-9-fluorenecarboxylic
acid. In an alternative workup with D2O a comparable yield of 9,0-dideuterio-9-fluorenol was obtained. These results provide evidence
for the intermediacy of vanadacycle 13 (Scheme 2). [d] In this run a ratio 1.25:1.00 molar equivalents of 10 to 1.00 equiv. of 9-fluorenone
was employed.
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Selective Epimetallating Vanadium(I) Reagents
strates with C=O and C=N bonds underwent either
epimetallation or reductive dimerization completely
(Scheme 2).
(5)
One peculiarity of the THF solution of VCl as prepared
is the presence of about 20% of the epimetallated product
of VCl with 1-butene (20). The intermediate 20 can be
trapped by carbonation to pentanoic acid (21) (Entry 8) or
with benzonitrile to produce butyl phenyl ketone (22) (En-
try 7). If desired, any 20 in the VCl solution can be removed
by disrupting 20 by THF evaporation in vacuo and there-
after adding fresh THF (Scheme 3).
Scheme 2.
Similar observations have been noted with CrCl but the
reductive dimer amounts to 90% or greater with this rea-
gent. The epimetallated product of benzaldehyde, acetophe-
none, benzophenone, 9-fluorenone and N-benzylidene-
methylamine with VCl, on the other hand, amounted to
20%, 45%, 51%, 43% and 48%, respectively, of the prod-
Scheme 3.
Although the N=N bond of azobenzene (Entry 9) and
ucts (Entries 1–4, 6). This epimetallated product 13 appears the strained C=C bond of acenaphthene (Entry 11) can be
to lead to the dimer 14 relatively slowly. In certain runs, epimetallated readily, C=C or CϵC bonds are not easily
support for such a vanadacyclopropane intermediate 13 attacked (Entries 13, 14, 15 and 17). Instead, VCl appears
was obtained by treating 13 with CO2 to produce the hy- to act as a source of free radicals and effects the isomeriza-
droxy acid 15 (E = O in Entry 4) or hydrolyzing with D2O tion of (Z)-stilbene to (E)-stilbene, the polymerization of
to form 16 (Entry 4). Finally, treating 14 with H2O resulted styrene and the C=C bond migration and (Z,E)-isomeriza-
in a mixture of the racemic and meso diols or diamines 17. tion of 4-phenyl-1-butene (Entries 14, 12, 15).
But in contrast with the high rac/meso ratios of 17 obtained
A typical conjugated diene, such as (E,E)-1,4-diphenyl-
with CrCl (3.0–6.0:1.0), the rac/meso ratios from VCl were 1,3-butadiene (23), does undergo ready epimetallation, ap-
much less selective (1–2:1.0). By employing a larger excess parently involving rearrangement of the 1,2-epimetallated
of VCl, the epimetallated product 13 could be further fa- intermediate (24a) to 1,4-epimetallated intermediate (25a)
vored over 14. But the CrCl reagent is clearly the choice for and of vanadocycle 25a to 26a + 26b (Entry 16).
fostering the reductive dimer and hence the resulting race-
mic dimer 17a.
Protonation of 26b could produce 25b or 27 (Scheme 4).
Although the epimetallation of 23 with VCl provides an
One special advantage of VCl may be the smooth dimer- interesting study of organometallic rearrangements, such re-
izing deoxygenation of certain ketones with VCl in refluxing duction of 1,3-dienes seems to offer no clean route as a
THF. Use of 1.25 equiv. of VCl with 9-fluorenone (18) gives preparative procedure.
essentially a quantitative yield of 9,9Ј-bifluorenylidene (19)
Finally, the epimetallations of certain σ-bonded sub-
(Entry 5) [Equation (5)].
strates has appeal in preparative reductions. Epoxides such
Scheme 4.
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4485

J. J. Eisch, P. O. Fregene
FULL PAPER
as (Z)-stilbene oxide undergo smooth deoxygenation to the Reductions of Organic Substrates with Lithium
thermodynamic mixture of 97:3 of E/Z-stilbenes (Entry 10). Vanadium(I) Dihydride (12)
Benzylic halides are dimerized principally to reduced di-
mers (Entries 18–21) but as with carbonyl substrates, mono-
Carbonyl and Imino Derivatives: A selected variety
meric reduction to hydrocarbon or halide occurs in signifi- of π-bonded organic substrates was treated with a THF
cant amounts (benzyl chloride: 24% toluene; benzal chlo- solution of two equiv. of LiVH2 (12) at 25 °C for 18 h
ride: 77% benzyl chloride; 9-bromofluorene: 35% fluorene (Table 2). As with VCl in THF, the starting LiVH2
in Entries 18, 19, 21). Thus VCl is again less selective than contained a considerable proportion of the epimetallated
CrCl for such reductive dimerizations. The inadequacy of adduct with 1-butene (28) (Scheme 5). The presence
VCl either for the dehalogenation or reductive dimerization of 28 was revealed in the reactions of 12 with CO2:
of aromatic halides is reflected in the low yields and selec- for carbonations begun at –78 °C and continued up to
tivity shown in Entries 22, 23 and 24. However, halonaph- 25 °C (Entry 2), CO2 insertions at both bond a and bond b
thalenes and halobiphenyls undergo high-yielding forma- occurred, resulting in the isolation of pentanoic acid
tion of the corresponding hydrocarbon (Entry 25).
(18%) and 2-methylbutanoic acid (2%). Interestingly,
Table 2. Reductions with lithium vanadium(I) dihydride, LiVH2 (12).
Entry Substrate[a]
Product(s)
Yield[b]
1
2
carbon dioxide (–78 °C)
carbon dioxide (–78 °C to 25 °C)
propylmalonic acid
pentanoic acid
2-methylbutanoic acid
butyl phenyl ketone
benzyl phenyl ketone
benzyl phenyl ketone
35
18
2
55
45
90
3
benzonitrile[c]
4
5
benzonitrile[d]
benzylideneaniline
1,2-dianilino-1,2-diphenylethane (67:33, rac/meso)
N-benzylaniline
91
6
6
7
8
2-naphthylideneaniline
1,2-dianilino-1,2-di-2-naphthylethane (100:0, rac:meso)
N-2-naphthylmethylaniline
N-benzylmethylamine
1,2-bis(N-methylamino)-1,2-diphenylethane (100:0 rac:meso)
4,5-diphenyl-1,3-bis(phenylmethylimino)-tetrahydroimidazole (73:27 rac:meso) 65
51
49
50
50
N-benzylidenemethylamine
(E,E)-benzaldehyde azine
benzaldehyde
10
95
95
85
15
84
82
87
85
30
70
29
71
70
30
85
15
70
30
94
100
95
82
12
9
10
11
9-fluorenylideneaniline
9-fluorenylideneaniline[e]
azobenzene
N-(9-fluorenyl)aniline
9,N-dideuterio-N-(9-fluorenyl)aniline
hydrazobenzene
aniline
9-fluorenol
9,O-dideuterio-9-fluorenol
diphenylmethanol
α-O-dideuteriodiphenylmethanol
1-phenylethanol
2,3-diphenyl-2,3-butanediol (81:19 rac:meso)
benzyl alcohol
1,2-diphenyl-1,2-ethanediol (80:20)
1,2-dibenzoylethane
acetophenone
12
13
14
15
16
9-fluorenone
9-fluorenone[e]
benzophenone
benzophenone[e]
acetophenone
17
18
19
20
benzaldehyde
α-bromoacetophenone
2-(N-ethanoylamino)benzophenone 2-methyl-3-phenylindole
2-(N-acetamido)diphenylmethanol
endo-2-borneol
(Ϯ) camphor
exo-2-borneol
benzoin
adamantanol
2-(α-hydroxylbenzyl)pyridine
1,4-diphenyl-2-butene (83:17 E/Z)
1,4-diphenyl-1-butene
stilbene (6.5:1.0, E/Z)
1-butanol
21
22
23
24
benzil
adamantanone
2-benzoylpyridine
(E,E)-1,4-diphenyl-1,3-butadiene
25
26
benzal chloride
tetrahydrofuran
94
__
[a] As with the runs with VCl in Table 1, all the foregoing runs involved a 1:2 molar equivalent ratio of organic substrate: LiVH2 (12)
with 1.5–3.0 mmol of organic substrate in 30–40 mL of pure THF for 12 h at 25Ϯ5 °C. It is important to note that VCl4 was the starting
material employed for the alkylative reduction with n-butyllithium to prepare the LiVH2 (12) used in the foregoing reactions; cf. the
detailed procedure in ref.[1]. [b] Cf. footnote b in Table 1. [c] The solution of the LiVH2 (12) in THF was used directly after the reaction
of VCl4 with five equivalents of n-butyllithium without any attempt to remove the 1-butene by-product. [d] The solution of the LiVH2
(12) in THF was freed of solvent and any epimetallated 1-butene under reduced pressure and the residual LiVH2/LiCl solid was then
redissolved in anhydrous THF that had been freshly distilled under argon. [e] Workup with D2O.
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Selective Epimetallating Vanadium(I) Reagents
when the carbonation was conducted at –78 °C only
(Entry 1), then a 35% yield of propylmalonic acid (31) was
formed.
(7)
The great preference for forming epimetallated monomer
is displayed with rigid and sterically hindered carbonyl and
imino derivatives, such as 9-fluorenone and 9-fluorenyl-
idene aniline (Entries 9, 10, 12 and 13). Epimetallated inter-
mediate 36, for example, formed from 9-fluorenone (18) in
over 80%, serves as a practical precursor to α-hydroxy acid
38, via 37,[15] to α-benzoyl alcohol 43, via 39, and poten-
tially to the unsymmetrical pinacol 42, via 41[13] (Scheme 6),
all in good yield. Such reactions of epimetallated adduct 36
appear to be feasible with corresponding adducts of hin-
dered ketones like adamantanone, benzophenone and 2-
benzoylpyridine.
Scheme 5.
Apparently the carbonated intermediate 29 isomerized
with enolate salt 30 being formed and the further carbona-
tion of 30 then ensued. Intermediate 28 also interfered in
reactions of 12 with benzonitrile: instead of the desired re-
duction by 12 (cf. infra), benzonitrile inserted almost quan-
titatively into 28 at bond a to form butyl phenyl ketone
upon hydrolysis (cf. Scheme 3). This interference in reagent
12 could be obviated by simply removing all the THF under
reduced pressure and readding fresh THF.
One of the striking differences in the reaction of LiVH2
with carbonyl and imine substrates (32), vs. that of LiCrH2,
is the greater selectivity of LiVH2 for forming the 1:1 epime-
tallated product [33, equation (6)]. The bonding in interme-
diate 33 was corroborated in several reactions by deuter-
iolytic workup to provide the expected dideuterio reduction
product or by carbonation to yield the α-hydroxy or α-
amino acid [cf. supra, Scheme 2 and ref.[14] (Entries 5, 6, 7,
9, 10, 12, 13, 14, 16, 17)].
(6)
Scheme 6.
In the reductive dimer formed in such reactions in yields
ranging from 10% to 70%, the racemic stereochemistry was
favored by 2–4 to 1.0 and in certain cases, exclusively over
Reactions of Benzonitrile
The reaction of benzonitrile (44) with LiVH2 forms a
the meso (Entries 5–7). This stereoselectivity could result sharp contrast with the vigorous and variegated reactions
from the steric orientation of the R and RЈ substituents in of LiCrH2 with such a nitrile. At 25 °C in THF the latter
the transition state (35) for C–C bond formation [Equation reagent converts 75% of benzonitrile, after hydrolysis, into
(7)]. Although the reduced dimers constitute a smaller pro- a mixture of benzaldehyde, benzil, 2,4,6-triphenyl-1,3,5-tri-
portion of the products, in some cases they are separable azine and 2,4,5-triphenylimidazole, in varying proportions
from the monomeric product and resolvable into racemic depending on the molar ratio of 6/nitrile.[12] First of all, it is
and meso isomers by column chromatography (Entries 5, 6, clear that the imidazole (45) is an artifact produced during
7, 16 and 17).
hydrolysis by the Radziszewski reaction[16] [Equation (8)].
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FULL PAPER
The requisite benzaldehyde and benzil arise apparently be revealed by cis-geometry of the olefin formed upon hy-
from the epimetallation and reductive dimerization of ben- drolysis (52a). Initial runs of the reaction in fact gave the
zonitrile by LiCrH2 (6) (Scheme 7), respectively.
cis-isomer of 1,4-diphenyl-2-butene (52a) as the principal
product, as well as (E)-1,4-diphenyl-1-butene as the minor
(51). But surprisingly, 1-phenyl-1,2,3,4-tetrahydronaphtha-
lene (53) was a significant by-product. However 53 was
shown to be an artifact produced by the 6  aq. HCl used
in the hydrolysis, which cyclized 51 and/or 52 into 53. Use
of water alone then yielded 82% of a Z/E mixture of 1,4-
diphenyl-2-butene in a 83:17 ratio of 52a and 52b and 12%
of (E)-1,4-diphenyl-1-butene (51). Treatment of a reaction
sample with D2O and subsequent 1H and 2H NMR spectral
analysis showed the presence of deuterium at C3 and C4 in
51 and C1 and C4 in 52a. The small content of E-isomer
52b in 52 is ascribed to the relatively slow protolysis by H2O
of the two V–C bonds in 50, by neutral H2O, permitting
Z/E isomerization of the intermediate 54 [Equation (9)].
Further studies of the reaction LiVH2 with such conjugated
dienes may lead to a useful method for cis-1,4-reductions.
(8)
Scheme 7.
The LiVH2 reagent, on the other hand, converts benzo-
nitrile into a product yielding upon hydrolysis benzyl
phenyl ketone (48) in high yield. This unprecedented re-
ductive dimerization may occur by the following pathway
(Scheme 8). The rearrangement of bridged dimer 46 to en-
amine 47 would yield upon hydrolysis, 48. This novel re-
ductive dimerization of nitriles may prove applicable to the
useful cyclization of α,ω-dinitriles. Reminiscent of the
Thorpe dimerization of nitriles or the Thorpe–Ziegler cycli-
zation of α,ω-dinitriles, this process differs from them in not
involving an enolizable α-carbon–hydrogen bond and thus
in no loss of a carbon atom.[17]
Scheme 9.
(9)
Scheme 8.
Analogous reactions of 12 involving intramolecular 1,4-
or 1,n-epimetallations are: a) the reduction of benzil to ben-
zoin (Entry 21); b) the coupling of the two carbonyl groups
1,2-Epimetallation vs. 1,4-Epimetallation in Conjugated
Substrates
Because LiVH2 is known to have the biradical VH2 in 2-(ethanoylamino)benzophenone (55) to produce the in-
anion, attack of 12 on conjugated systems (Scheme 9), such dole 56 (Equation 10, Entry 19);[18] and c) the reaction of
as 1,4-diphenyl-1,3-butadiene (49) could well result in 1,2- 12 with cinnamaldehyde anil (57) (1:1) to yield principally
and 1,4-epimetallations. The latter mode of addition would 58 (Equation 11).
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Selective Epimetallating Vanadium(I) Reagents
(10)
(11)
Scheme 10.
Coupling or σ-epimetallation of benzylic and α-bromo-
carbonyl derivatives by 12 (1:2 molar ratio) occurs in good
to high yields. Examples are the reactions of benzyl chloride
to bibenzyl (100%), of benzal chloride to (E)-stilbene
(94%), of benzo trichloride to stilbene (84% and E/Z ratio
of 5.3:1.0) and bibenzyl (12%), of dichlorodiphenylmethane
to 1,1,2,2-tetraphenylethene (93%) and of α-bromoace-
tophenone to 1,2-dibenzoylethane (70%). Aromatic halides
on the other hand were coupled and dehalogenated in low
yields. In pointed contrast to LiCrH2, finally, LiVH2 failed
to cleave the C–O, C–N and C–S bonds of aromatic ethers,
amines or sulfides, confirming the chromium reagent as
much more reactive in σ-bond epimetallations.[12] The THF
solvent underwent reductive cleavage to form 1-butanol
only with slow-reacting organic substrates.
of association or ion-clustering of any of the four reagents,
nor the degree of solvation with the THF medium.
Of the above differences between these vanadium and
chromium reagents, we proposed that the principal contrib-
uting factor to the greater reactivity of LiCrH2 is the single
available unpaired electron on Cr(I). With CrCl, the un-
paired electron may not be available until a dimer or oligo-
mer (CrCl)n dissociates. In either case, when monomeric
(·CrCl) or LiCrH2 engages in oxidative addition or epi-
metallation (Scheme 11), the intermediate formed, 62,
should still possess an unpaired electron. With an unpaired
electron the epimetallated adduct 62 should tend to rupture
rapidly to yield radical 63, where the free electron can be
transferred to carbon, where delocalization and electrone-
gativity would enhance radical stability.
A final such striking example of the selectivity of LiVH2
in the coupling of imines is the good yield (68%) of 60 as
a 73:27 mixture of racemic and meso isomers after reaction
of (E,E)-benzalazine (59) with 12 and hydrolysis. That 60
could be formed in such a high yield with relatively little
cleavage of the weak N–N bond in any precursors is a fur-
ther indication of the milder reducing action of 12. It is
likely that 60 is actually formed in the hydrolysis step, where
the coupled intermediate 61 undergoes a condensation reac-
tion with the benzaldehyde arising from the reductive cleav-
age of 59 and subsequent hydrolysis (Scheme 10).
Scheme 11.
Possible Sources of the Reactivity Differences Between
Vanadium(I) Chloride (11) and Lithium Vanadium(I)
Dihydride (12) vis-à-vis their Chromium Counterparts
In sharp contrast, biradical Li+ :VH2 and potentially
available biradical :VCl, could epimetallate 32 with com-
The discernible atomic differences between the empirical plete pairing of available electrons in 64 (Scheme 12). For-
formulas of the vanadium(I) reagents, VCl (11) and LiVH2 mation of diamagnetic 64 should contribute to its kinetic
(12), and their chromium(I) counterparts, CrCl (10) and stability and thus slow down its conversion to open-chain
LiCrH2 (6) are the following: 1) LiVH2 has one less proton biradical 65. This proposal would explain why the epimetal-
in the metal nucleus (23) than does chromium(24); 2) lated products from 32 and LiVH2 are often the major
LiVH2 has two unpaired electrons, while LiCrH2 has only products (33), while 32 and LiCrH2 often yield more of the
one unpaired electron; 3) on the Allred–Rochow scale, the reductive dimers (34).
chromium center is somewhat more electronegative (1.56)
Finally, the reasons for the greater reactivity of LiCrH2
than the vanadium center (1.45); and 4) the atomic radius over LiVH2 in the epimetallation or cleavage of σ-bonds
of the vanadium atom is slightly larger (1.34 Å) than that [see Equation (4)] and the nature of the reaction mechanism
of chromium (1.27 Å). Nothing is known about the degree remain unclear and are the goal of continuing studies.
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J. J. Eisch, P. O. Fregene
FULL PAPER
organic products, which were obtained in this investigation of the
reduction capabilities of VCl (11) and LiVH2 (12) (Table 1 and
Table 2) and are not found in standard spectral compilations,[20,21]
are given here. The following 1H and 13C (decoupled) NMR spectra
were recorded with a Bruker AM-360 spectrometer at 360 MHz in
CDCl3 solution in ppm on the δ scale.
Such data served to verify the correct overall structures of the reac-
tion products, as well as assessing the racemic/meso isomeric ratio
where such stereochemical variation was possible, as in the bimo-
lecular reductions of aldehydes, aldimines and unsymmetrical
ketones, exemplified by benzaldehyde, benzylidenemethylamine and
acetophenone, respectively (Entries 1, 6, 2 in Table 1; Entries 17, 5,
16 in Table 2). From the known 1H NMR spectra of meso- and
rac-isomers of benzaldehyde’s dimeric diol, the methine H on the
chiral carbon in racemic isomer 66 occurs at a lower field, 4.67 ppm
than the methine H in the meso isomer, 4.82 ppm.
Scheme 12.
Experimental Section
General Experimental Procedures and Starting Materials: All pro-
cedures involving the purification of reaction solvents, distillation
of reagents, the preparations of vanadium(I) chloride (11), lithium
vanadium(I) dihydride (12) and their subsequent measurements or
reactions with organic substrates were conducted under a positive
atmospheric pressure of anhydrous, deoxygenated argon employing
vacuum techniques and with standard Schlenk apparatus. The dry-
ing and deoxygenation of argon, as well as the solvents, such as
tetrahydrofuran, toluene and hexane, used in the reactions were
carried out according to established procedures.[19]
The dimers of benzylidenemethylamine show a similar relationship:
racemic methine H at δ = 3.63 ppm and the meso methine H at δ
= 4.05 ppm. From the integration of such peaks, the rac-meso iso-
meric ratio was estimated. In the case where only one methine H
singlet was found in this region, as with the dimer from 2-naphthyl-
ideneaniline, it was assumed that the rac-isomer was formed exclu-
sively due to steric hindrance in the bimolecular coupling (compare
transition state 35).
9,9Ј-Bifluorenylidene: 1H NMR: δ = 8.36 (3, 4 H), 7.67 (d, 4 H),
7.30 (t, 4 H), 7.19 (dd, 4 H) ppm. 13C NMR: δ = 141.32, 141.0,
138.29, 129.13, 126.82, 126.71, 119.86 ppm.
The n-butyllithium in hexane was purchased from Sigma–Aldrich
in Sure Seal bottles and was used at the stated concentration as
received, uniformly 2.5 . The anhydrous vanadium(III) chloride
was purchased from Sigma–Aldrich at 97% purity and the vanadi-
um(IV) chloride in at least 99% purity.
Preparations of Vanadium(I) Chloride (12) and Lithium Vandium(I)
Dihydride (12) and Their Gasometric, Infrared Spectroscopic and
Electronic Paramagnetic Resonance Analyses: Detailed procedures
for the preparation of VCl (11) in THF from VCl3 or VCl4, as well
as the preparation of LiVH2 (12) from VCl4 (the preferred method),
are given in the preceding publication.[1] Likewise, all apparatus
and instrumentation required for the gasometric, IR spectral and
EPR analyses are described or specified in the same reference.
1
9,9Ј-Bifluorenyl: H NMR: δ = 7.64 (d, 4 H), 7.26 (t, 4 H), 7.08 (t,
4 H), 6.95 (d, 4 H), 4.83 (s, 2 H) ppm. 13C NMR: δ = 144.67,
141.54, 127.27, 126.69, 124.07, 119.62, 49.84 ppm.
1
9,9Ј-Bifluorenyl-9,9Ј-diol: H NMR: δ = 7.38 (m, 5 H), 7.24 (m, 6
H), 7.06 (m, 5 H), 3.17 (s, 2 H) ppm.
rac-1,2-Diphenylethane-1,2-diol: 1H NMR: δ = 7.23–7.11 (m, 10 H),
4.67 (s, 2 methine H), 2.92 (s, 2 H) ppm. 13C NMR: δ = 139.89,
127.87, 126.92, 79.64 ppm.
Product Identification from the Reactions of VCl (11) or LiVH2 (12)
with Various Organic Substrates in THF: Product identification of
1
meso-1,2-Diphenylethane-1,2-diol: H NMR: δ = 7.33–7.23 (m, 10
H), 4.82 (s, 2 methine H), 2.37 (s, 2 H) ppm.
rac-2,3-Diphenylbutane-2,3-diol: 1H NMR: δ = 7.25–7.13 (m, 10 H),
2.54 (s, 2 H), 1.49 (s, 6 methyl H). 13C NMR: 143.46, 127.35,
127.15, 127.03, 78.85, 24.95 ppm.
1
known compounds was achieved principally by comparison of H
and 13C NMR spectra of such reaction products with those spectra
of authentic compounds given in the literature.[20,21] Similarly,
product yields from such reactions were calculated based on inte-
gration of the respective NMR proton peaks, except for carboxylic
acids, where the yields were based on the weight of product ob-
tained.
meso-2,3-Diphenylbutane-2,3-diol: 7.25–7.13 (m, 10 H), 2.54 (s, 2
H), 1.49 (s, 6 methyl H). 13C NMR: δ = 143.46, 127.35, 127.15,
127.03, 78.6 (diagnostic for meso), 24.95 ppm.
rac-1,2-Bis(methylamino)-1,2-diphenylethane: 1H NMR: δ = 7.55–
7.33 (m, 10 H), 3.63 (s, 2 methine H), 2.08 (6 H), 1.51 (2 H, br. s).
13C NMR: 140.7, 128.4, 127.6, 126.6, 70.9, 34.3 ppm.
The 1H NMR spectroscopic data are reported on the δ scale in
parts per million with reference to an internal standard of tet-
ramethylsilane (TMS) for solutions in deuteriated chloroform
(CDCl3) or deuteriated dimethyl sulfoxide ([D6]DMSO) solvent.
The 13C NMR spectroscopic data are reported on the δ scale in
parts per million with reference to deuteriated solvents. Coupling
constants between adjacent, chemical different Hs and falling in
1
meso-1,2-Bis(methylamino)-1,2-diphenylethane: H NMR: diagnos-
tic singlet for 2 methine H at δ = 4.05 ppm.
(E)-1,4-Diphenyl-1-butene: 1H NMR: δ = 7.34–7.16 (m, 10 H), 6.41
(d, 1 H), 6.25 (dt, 1 H), 2.79 (t, 2 H), 2.52 (q, 2 H). 13C NMR:
141.17, 137.7, 129.9, 128.5, 128.3, 126.9, 125.9, 125.86, 35.9, 34.87
ppm.
1
the usual range have been omitted. In the next section H and 13C
NMR spectroscopic data are given for the unusual organic prod-
ucts and for the stereochemical assignments of the meso- and race-
mic-isomers obtained.
1
1H and 13C NMR Spectral Data of Unusual Organic Products En-
(Z)-1,4-Diphenyl-2-butene: H NMR: δ = 7.15 (s, 10 H), 5.70 (t, 2
H), 3.4 (d, 4 H) ppm.
1
countered in This Study: The H and 13C NMR spectra of certain
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Selective Epimetallating Vanadium(I) Reagents
(E)-1,4-Diphenyl-2-butene: 1H NMR: δ = 7.21 (br. s, 10 H), 5.66
(m, 2 H), 3.39 (d, 4 H) ppm.
140 mg of a pale yellow liquid as the aqueous organic extract was
found to be benzylamine in 25% overall yield.
rac-1,2-Dianilino-1,2-diphenylethane: 1H NMR: δ = 7.27–7.14 (m,
10), 7.10–7.06 (t, 4 H), 6.67 (t, 2 H), 6.51 (d, 4 H), 4.57 (s, 2 methine
H). 13C NMR: 146.9, 139.9, 129.1, 128.4, 127.5, 118.1, 114.1, 64.0
ppm.
Reactions of Benzonitrile (44) with LiVH2 (12) Prepared from VCl4.
a) Reagent LiVH2 Containing 1-Butene: A solution of LiVH2
(2.4 mmol) in 40 mL THF was treated with benzonitrile (0.12 mL,
1.2 mmol) at room temperature for 12 h. Hydrolytic workup
yielded 240 mg of a light red liquid consisting of 45% benzyl
phenyl ketone and 55% of butyl phenyl ketone.
meso-1,2-Dianilino-1,2-diphenylethane: 1H NMR: δ = 7.05–7.01 (m,
10 H), 6.93 (q, 4 H), 6.63 (t, 2 H), 6.48 (d, 4 H), 4.94 (s, 2 methine
H) ppm.
b) Reagent LiVH2 Freed of 1-Butene: In an effort to prevent the
interference of 1-butene with product distribution, a solution of
LiVH2 (12) (2.0 mmol) in 20 mL THF was subjected to reduced
pressure at room temp. and most of the volatiles removed. Then
fresh dry and deoxygenated THF (distilled under argon) was added
and the resulting solution was again allowed to react with benzoni-
trile (0.20 mL, 1.0 mmol) at room temperature for 12 h. Hydrolytic
workup afforded 280 mg of a reddish liquid consisting of essentially
pure benzyl phenyl ketone and amounting to a 90% yield.
rac-1,2-Dianilino-1,2-di(2-naphthyl)ethane (assumed stereochemis-
try): 1H NMR: diagnostic one singlet at δ = 5.55 ppm for 2 methine
H.
Specific Procedures for Certain Reductions with Lithium Vanadi-
um(I) Dihydride (12): Although the general procedures described in
footnote [a] of Tables 1 and 2 are sufficient for guidance in conduct-
ing most reductions with VCl (11) or LiVH2 (12), certain re-
ductions with LiVH2 require the more detailed descriptions given
here.
Reactions of 9-Fluorenone (18) with LiVH2 (12) and Treatment of
the Resulting Epimetallated Adduct 36 with Benzonitrile: A solution
of LiVH2 (12, 3.2 mmol) in 10 mL of THF was allowed to react
with a solution of 9-fluorenone (18, 288 mg, 1.6 mmol) in 5 mL of
THF for 6 h at 25Ϯ5 °C. Thereupon the resulting reaction mixture
was treated with benzonitrile (44, 165 mg, 1.6 mmol) and the solu-
tion stirred for an additional 12 h. Usual hydrolytic workup with
0.1  aqueous HCl and ether extraction yielded 242 mg of 9-benz-
imidyl-9-fluorenol (40) in 97% purity, containing 2% of 9-fluorenol
and 1% of fluorene as impurities. The overall yield of ketimine 40
was 60 %.
9-Benzimidyl-9-fluorenol (40): 1H NMR (CDCl3): δ = 7.59–7.53 (m,
2 H), 7.46–7.39 (m, 2 H), 7.33–7.26 (m, 5 H), 7.03 (t, 2 H), 6.93
(m, 2 H), 6.44 (s, 1 H), 5.18 (br., 1 H) ppm. 13C NMR (CDCl3): δ
= 157.7, 145.7, 140.8, 130.6, 129.4, 128.2, 127.9, 127.6, 127.2, 124.5,
120.0, 83.8 ppm.
Reactions of (E,E)-Benzaldehyde Azine (59) with LiVH2 (12). a) 1:1
Ratio of 59 and 12: A solution of LiVH2 (12, 4.8 mmol) in 40 mL
of THF was treated with a solution of the azine (1.00 g, 4.8 mmol)
in 20 mL of THF at 25Ϯ5 °C for 12 h. Hydrolysis of the reaction
mixture with 1.0  aqueous HCl, ether extraction, drying of the
ether extract and removal of the ether gave an organic residue of
410 mg (51% calculated as 60a and 60b with the assumption
3 equiv. of 59 are theoretically required to produce 1.0 equiv. of
60). Flash column chromatography on silica gel using a 1:50 ethyl
acetate/hexane eluent gave a composition of 65% of rac-4,5-di-
phenyl-1,3-bis(phenylmethylimino)tetrahydroimidazole (60a), 24%
of meso-4,5-diphenyl-1,3-bis(phenylmethylimino)tetrahydroimid-
azole (60b), 8% benzaldehyde and 1% of the azine.
Basification of the original aqueous layer and ether extraction
yielded 100 mg of benzylamine and the rac/meso-1,2-diphenyl-1,2-
ethylenediamines in yields of about 6% of each.
The ketimine 40 proved resistant to hydrolysis and refluxing a sam-
ple in 3  aqueous H2SO4 for several hours, basifying with aqueous
NaOH and isolating the organic product gave only a 45% yield of
9-benzoyl-9-fluorenol (43) after column chromatographic purifica-
tion, m.p. 120–122 °C.
meso-4,5-Diphenyl-1,3-bis(phenylmethylimino)tetrahydroimidazole
1
(60b): H NMR (CDCl3): δ = 8.00 (d, 2 H), 7.90–7.00 (m 30 H),
5.60 (s, 1 H), 5.10 (s, 2 H) ppm. 13C NMR (CDCl3): δ = 139.9,
137.8, 135.9, 129.0–126.2, 102.7, 86.4, 76.4, 69.7 ppm.
1
9-Benzoyl-9-fluorenol (43): H NMR (CDCl3): δ = 7.74 (m, 2 H),
7.41 (td, 2 H), 7.35 (m, 2 H), 7.31–7.20 (m, 5 H), 7.07 (m, 2 H),
5.67 (br., 1 H) ppm. 13C NMR (CDCl3): δ = 199.7, 146.0, 141.2,
133.0, 129.9, 129.2, 128.7, 128.2, 124.5, 120.8, 86.52 ppm.
rac-4,5-Diphenyl-1,3-bis(phenylmethylimino)tetrahydroimidazole
(60a): H NMR (CDCl3): δ = 7.72 (d, 2 H), 7.70–7.02 (m, 28 H),
6.93 (s, 1 H), 4.88 (s, 1 H), 4.68 (d, 1 H), 4.66 (d, 1 H) ppm.
1
Samples of (60a) and (60b), separated by column chromatography
on silica gel with an eluent of ethyl acetate and hexane in a 1:50
ratio, were separately subjected to mass spectrometry (70 eV, elec-
trospray with NaI). Both presented similar spectra: (529) [M + Na],
(530) [M + 1 + Na], (506) [M], (505) [M –1], (402) [M –104]
(-PhCH=N), (403) [M –103] (-PhCHϵN), (–299) [M] (loss of Ph
and PhCH=N). Such fragments are consistent with the structures
of 60a (rac) and 60b (meso), which can lose H+, Ph–C+=NH and
Ph–CϵN sequentially, at the weak PhHC=N–N bonds.
Acknowledgments
The authors are grateful for the financial support of this research
by the Boulder Scientific Company of Mead, Colorado and by the
Alexander von Humboldt Foundation of Bonn, Germany, which
latter source provided the Senior Scientist Award to J. J. E., en-
abling the preparation of this manuscript while the principal inves-
tigator was in residence at the Technische Universität München,
Germany, on sabbatical leave. This author remains appreciative of
the hospitality extended to him by Professor Wolfgang Herrmann,
President of the TUM, during his stay in the Anorganisch-Chem-
isches Institut for the academic year of 2005–2006. Valuable techni-
cal assistance and advice were provided by Professor John N. Gitua
of Drake University and by Dr. Joseph R. Alila, through his doc-
toral dissertation on the chromium reagents, 6 and 10 (SUNY-
Binghamton, 1999) and his research records. Finally, the senior
author is indebted to Professor Udo Brinker of the University of
Vienna for his insights into carbene and small-ring chemistry.
b) 1:2 Ratio of 59 and 12: In a similar experiment to investigate the
effect of stoichiometry on product distribution and yield, a solution
of the azine (540 mg, 2.6 mmol) in 5 mL THF, was admixed with
a solution of LiVH2 (5.1 mmol) in 40 mL THF and treated at room
temperature for 12 h. Upon hydrolysis of the black reaction mix-
ture a vigorous exothermic reaction characterized by gas evolution
ensued. Hydrolytic workup gave 300 mg of a light brown solid
(≈ 65% as 60a and 60b) as the neutral organic extract consisting of
10% benzaldehyde, 60% of 60a and 5% of 60b. On the other hand
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J. J. Eisch, P. O. Fregene
FULL PAPER
[9]
J. J. Eisch, X. Shi, F. A. Owuor, Organometallics 1998, 17, 5219.
J. J. Eisch, S. Dutta, 2005, unpublished studies.
J. J. Eisch, J. R. Alila, Organometallics 1999, 18, 2930–2932.
J. J. Eisch, J. R. Alila, Organometallics 2000, 19, 1211–1213.
J. J. Eisch and P. O. Fregene, 2008, studies in progress: Upon
warming from –78 °C to 0 °C LiTiH3 decomposes into LiH, Ti
and H2.
[1] J. J. Eisch, P. O. Fregene, D. C. Doetschman, Eur. J. Org. Chem.
2008, 2825–2835.
[10]
[11]
[12]
[13]
[2] a) K. Ziegler, E. Holzkamp, H. Breil, H. Martin, Angew. Chem.
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scientific recognition for this revolutionary discovery by the
joint Nobel prize, the intellectual property rights for such poly-
merization discoveries have long been a matter of legal dispute.
A detailed account of the multiple lawsuits extending over 50
years has been published from the Ziegler group’s vantage
point by Ziegler’s living research associate: H. Martin, Poly-
mere und Patente, Wiley-VCH, Weinheim, 2002.
[3] A remarkably reliable analysis covering the copious patents in-
volving Zieger-Natta technology filed during the first 25 years
has appeared: J. Boor Jr, Ziegler–Natta Catalysts and Polymeri-
zation, Academic Press, New York, 1979, 670 pp.
[4] In three such seminal studies various subvalent titanium salts,
all of ill-defined oxidation state, were generated by reducing
TiCl3 or TiCl4 variously with LiAlH4, Mg, Al or Zn and em-
ploying the ill-defined reduced titanium reagents with car-
bonyl, olefinic, acetylenic or epoxy substrates for preparative
purposes: a) T. Mukaiyama, T. Sato, J. Hanna, Chem. Lett.
1973, 1041; b) S. Tyrlik, I. Wolochowicz, Bull. Soc. Chim. Fr.
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[14]
[15]
J. J. Eisch, J. Organomet. Chem. 2001, 617–618, 148–157.
J. J. Eisch, P. O. Fregene, J. N. Gitua, J. Organomet. Chem.
2007, 692, 4647–4653.
[16] B. Radziszewski, Ber. Dtsch. Chem. Ges. 1911, 44, 22.
[17] a) Review of the Thorpe reaction: J. P. Schaefer, J. J. Bloom-
field, Org. React. 1967, 15, 1; review of the Thorpe–Ziegler α,ω-
dinitrile cyclization: K. Ziegler, Houben-Weyl Methoden der
Organischen Chemie, 1955, 4/2, 758; b) The potential advantage
of this LiVH2 cyclization of α,ω-dinitriles over the Thorpe–
Ziegler method is that simple hydrolytic workup would furnish
the desired cyclic ketone, instead of the hydrolysis and decar-
boxylation of the α-cyano imine that would then require the
loss of a carbon atom.
[18] This novel synthesis of indoles was first realized by A.
Fürstner’s group by use of a combination of TiCl3 and Zn
metal, but the nature of the actual Ti reductant was not estab-
lished: A. Fürstner, B. Bogdanovic, Angew. Chem. Int. Ed.
Engl. 1996, 35, 2442–2469.
[19] Detailed descriptions of appropriate techniques for working
with air- and moisture-sensitive organometallics can be found
in: J. J. Eisch, Organometallic Syntheses, vol. 2, Academic Press,
New York, 1981, pp. 1–84.
[5] The role of subvalent transition-metal salts in organic re-
ductions, which had been reported prior to 1996, has received
abundant review: a) A. Fürstner, Angew. Chem. Int. Ed. Engl.
1993, 32, 164; b) A. Fürstner, B. Bogdanovic, Angew. Chem.
Int. Ed. Engl. 1996, 35, 2442; c) A. Fürstner (Eds.), Active Met-
als, VCH, Weinheim, 1996.
[20] J. C. Pourhert, J. Behnke (Eds.), Aldrich Library of 13C and H
1
FT-NMR Spectra, vol. 1–2, first edition, Aldrich Chemical Co.,
Milwaukee, 1993.
[21] J. C. Pourhert, J. Behnke (Eds.), Aldrich Library of 13C and H
1
[6] J. J. Eisch, X. Shi, J. R. Alila, S. Thiele, Chem. Ber./Recueil
1997, 130, 1175–1187.
FT-NMR Spectra, third edition, Aldrich Chemical Co., Mil-
waukee, 1981.
[7] J. J. Eisch, X. Shi, J. Lasota, Naturforschung, Teil B 1995, 50,
342–350.
Received: May 8, 2008
Published Online: July 30, 2008
[8] J. J. Eisch, J. N. Gitua, P. O. Otieno, X. Shi, J. Organomet.
Chem. 2001, 624, 229–238.
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