'GaI': A new reagent for chemo- and diastereoselective C-C bond forming reactions

Article abstract of DOI:10.1039/b613669a

The potential of 'GaI' as a reductant in organic transformations, in particular C-C bond forming reactions involving α-functionalised ketones, has been investigated. Of most interest are the diastereoselective aldol coupling reactions of the α-alkoxy ketones, PhC(O)C(H)(OR)Ph, R = Me, Et or ⁱPr, which give the novel γ-alkoxy, β-hydroxy ketones, PhC(O)C(H)(Ph)C(OH)(Ph)C(H)(OR)Ph, containing three contiguous stereogenic centres. The diastereostereoselectivity of these reactions was established from NMR spectroscopic and X-ray crystallographic studies of the products. When R = Me, the 2R,3S,4R/2S,3R,4S-enantiomeric pair is formed, whereas when R = Et or ⁱPr, 2R, 3R, 4S/2S, 3S, 4R-diastereoisomers result. These differences are rationalised in terms of the likely transition states of the reactions. The same products are not formed when higher oxidation salts of gallium, or InI, are employed as the inorganic reagent. The reactivity of "GaI" towards α-halo ketones, a 1,2-diketone and α,β-unsaturated ketones has also been explored. Again, the outcomes of these reactions have been compared to those involving Ga(ii) and Ga(iii) reagents. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.

Full text of DOI:10.1039/b613669a

View Article Online / Journal Homepage / Table of Contents for this issue
PAPER
www.rsc.org/njc | New Journal of Chemistry
‘GaI’: A new reagent for chemo- and diastereoselective C–C bond
forming reactionsw
Shaun P. Green, Cameron Jones,* Andreas Stasch and Richard P. Rose
Received (in Durham, UK) 20th September 2006, Accepted 7th November 2006
First published as an Advance Article on the web 8th December 2006
DOI: 10.1039/b613669a
The potential of ‘GaI’ as a reductant in organic transformations, in particular C–C bond forming
reactions involving a-functionalised ketones, has been investigated. Of most interest are the
diastereoselective aldol coupling reactions of the a-alkoxy ketones, PhC(O)C(H)(OR)Ph,
i
R = Me, Et or Pr, which give the novel g-alkoxy, b-hydroxy ketones,
PhC(O)C(H)(Ph)C(OH)(Ph)C(H)(OR)Ph, containing three contiguous stereogenic centres. The
diastereostereoselectivity of these reactions was established from NMR spectroscopic and X-ray
crystallographic studies of the products. When R = Me, the 2R,3S,4R/2S,3R,4S-enantiomeric
i
pair is formed, whereas when R = Et or Pr, 2R, 3R, 4S/2S, 3S, 4R-diastereoisomers result.
These differences are rationalised in terms of the likely transition states of the reactions. The same
products are not formed when higher oxidation salts of gallium, or InI, are employed as the
inorganic reagent. The reactivity of ‘‘GaI’’ towards a-halo ketones, a 1,2-diketone and
a,b-unsaturated ketones has also been explored. Again, the outcomes of these reactions have
been compared to those involving Ga(II) and Ga(III) reagents.
Our interest in low oxidation state gallium chemistry largely
Introduction
involves the stabilisation and coordination chemistry of gal-
lium(I) N-heterocyclic carbene analogues.5 The most impor-
C–C bond forming reactions are fundamental to organic
synthesis and have been carried out using inorganic and
tant starting material in the synthesis of such heterocycles is
Green’s ‘‘GaI’’ which acts as a source of gallium(I) iodide.6
organometallic reagents incorporating metals from across
the periodic table. From group 13, boron(III) and aluminiu-
This insoluble green powder is straightforwardly prepared by
m(III) compounds have been amongst the widely used reagents
the reaction of gallium metal with one half of an equivalent of
for this purpose. More recently, indium compounds have
diiodine in toluene under ultrasonic conditions (ultrasonic
found increasing usage in organic synthetic methodology. This
bath). Although it is very oxygen sensitive, it is thermally
can involve reagents with indium in the +3 oxidation state,
stable and can be stored indefinitely under an inert atmosphere
but there is an escalating interest in the exploitation of indium
without loss of activity. Although its formulation is not
metal and indium(I) halides as reductants in processes such as
definitely known, the results of a Raman spectroscopic study
Barbier allylations, Reformatsky reactions, aldol additions
suggest it predominately consists of the mixed oxidation salt,
and propargylation reactions.1,2 Although not as widely stu-
I
Ga2 [Ga2III6], with an average gallium oxidation state
of +1.5.7
died, gallium metal is beginning to be accepted as a reagent in
a similar array of reactions.2,3
In preliminary studies, we have shown that this material is,
Low oxidation state gallium halides have been almost
not surprisingly, a more potent reducing reagent than InI. For
completely neglected as reducing agents in C–C bond forming
example, it can facilely reductively couple diynes (to give ene-
diynes)8 or bulky 2-(imino)pyridines9 that are unreactive to-
reactions. The reasons for this most likely include the fact that
the former are not commercially available, and are more
wards the indium reagent. Given the apparent chemoselec-
oxygen and moisture sensitive than their indium counterparts.
tivity of ‘‘GaI’’ over InI, we were keen to extend our studies
Indeed, prior to our involvement in this area, it appears that
into its use in C–C bond forming reactions. In this paper we
only two reports4 have detailed the employment of a gallium
detail its unusual reactivity towards a-alkoxy ketones, a-halo
sub-halide in organic synthesis. In these, Saigo et al. described
ketones and a-diketones, which in the case of a-alkoxy ke-
the use of gallium(II) chloride (which actually exists as a mixed
oxidation salt, GaI[GaIIICl4]) in the one-pot ‘‘reductive Frie-
tones, leads to the diastereoselective formation of g-alkoxy b-
hydroxy ketones with three contiguous stereogenic centres.
del–Crafts’’ coupling reactions of carbonyl compounds or
dimethylacetals with aromatics.
Results and discussion
(i) Aldol-type coupling reactions of a-alkoxy ketones
Centre for Fundamental and Applied Main Group Chemistry, School
of Chemistry, Main Building, Cardiff University, Cardiff, UK CF10
Strong reducing agents such as SmI2 have been shown to
3AT. E-mail: Jonesca6@cardiff.ac.uk
reduce a-alkoxy ketones, e.g. benzoin methyl ether, to the
corresponding ketone, e.g. deoxybenzoin, under mild, neutral
w Electronic supplementary information (ESI) available: ORTEP dia-
grams for 10 and 14. See DOI: 10.1039/b613669a
ꢀc
This journal is the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2007
New J. Chem., 2007, 31, 127–134 | 127

View Article Online
conditions.10 In attempts to carry out similar reductions of a-
alkoxy ketones with ‘‘GaI’’, deoxybenzoin, 4, was formed but
unexpected C–C coupled products also resulted. The reactions
of benzoin methyl ether 1, benzoin ethyl ether 2 and benzoin
isopropyl ether 3, with four equivalents of ‘‘GaI’’ were carried
out in toluene, at À78 1C, with subsequent slow warming to
room temperature. These afforded the novel tri-functional
aldol coupled products 1a (2R,3S,4R/2S,3R,4S-product), 2a
and 3a (2R,3R,4S/2S,3S,4R-products), respectively, with com-
plete diastereocontrol within detection limits (see Table 1).
The reactions are thought to proceed via an initial reduction
of the substrate to generate short-lived gallium-enolates
(assumed to exist as their E-isomers), ‘‘[(RO)IGa{OC(Ph)Q
C(Ph)(H)}]’’ 5, which upon formation, undergo aldol-type
reactions with unreacted substrate to give the observed pro-
ducts. NMR spectroscopic studies of the reaction mixtures
prior to aqueous work-up did not show any evidence of 5 or
the expected gallium alkoxide conjugate bases of 1a–3a.
Instead, only 4 and the quenched products were present. This
suggests that product quenching via proton abstraction from
the toluene reaction solvent or another reaction component
readily occurs. The increasing yield of 4 with increasing size of
R could, therefore, be explained by a competition between
solvent quenching of 5 (to give 4) and its nucleophilic attack
on the a-alkoxy ketone substrate. The latter process would,
presumably, be slowed with increasing size of the alkoxy
substituent, thus favouring the formation of 4. When the
reactions were repeated utilising benzene as the solvent, the
resultant yields and diastereoselectivities were nearly identical
to the toluene reactions. Intriguingly, when hexane was used as
a solvent no reactions occurred. One explanation for this is
that arene solvents are required to partly solubilise the ‘‘GaI’’
reagent. Indeed, it is well known that Ga(I) salts engage in p-
arene interactions in solution.11
The diastereoselectivity of these reactions is interesting, but
even more so is the change in the diastereoisomer formed upon
changing the size of the substrate alkoxy group. It cannot be
sure why these differences occur but analogies can be drawn
with the previously reported additions of a-stannyl esters12 or
indium enolates13 towards a-alkoxy ketones which give syn-
products (cf. formation of 1a) with a very high degree of
diasteroselectivity. It was proposed that this selectivity arose
from a steric control of the enolate attack imposed by chelation
of the substrate to the tin or indium centre prior to addition. In
contrast, additions of indium enolates to simple ketones were
found to proceed diastereoselectively to give anti-products (cf.
formation of 2a and 3a). Here, six-membered cyclic transition
states were used to explain the selectivity of the reactions. In our
systems, it is feasible that the reaction of benzoin methyl ether
with ‘‘GaI’’ could proceed via a chelated cyclic transition state
(Scheme 1) which when quenched would lead to the observed
diastereoisomer, 1a. It is possible that the bulkier alkoxy
substituents of 2 and 3 preclude chelated transition states in
their reactions with ‘‘GaI’’ and instead six-membered transition
states, akin to those of indium enolate additions to simple
ketones, lead to 2a and 3a upon quenching. If this is the case,
the stereo-control of these reactions is dominated by the
electrophillic substrate rather than the enolate. It is possible
that the cyclic transition state that gave 2a and 3a is stabilised
by chelation of its alkoxy and ketone O-centres to gallium salts
(e.g. GaI3 from the disproportionation of ‘‘GaI’’6a) which are
likely to be present in the reaction mixture.
i
Table 1 Products from the reactions of a-alkoxy ketones, PhC(O)C(OR)Ph (R = Me, Et or Pr), with ‘‘GaI’’
Substrate
Products (yield)a
a
Only one enantiomer of each product is shown. Diastereoselectivities of the products are 499% in all cases.
ꢀc
This journal is the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2007
128 | New J. Chem., 2007, 31, 127–134

View Article Online
Scheme 1 Proposed mechanisms for the formation of 1a–3a. (i) ‘‘GaI’’, toluene; (ii) quench.
As the formulation of ‘‘GaI’’ is not definitely known, but is
believed to include the mixed oxidation salt, GaI2[GaII2I6], it
cannot be sure if the active component of the reagent is the
Ga(I) cation, the Ga(II) anion, or both. In addition, ‘‘GaI’’ is
well known to disproportionate to Ga metal and GaI3 in the
presence of Lewis base donor sites,6a as are present in 1–3.
Therefore, 1 was reacted with several Ga(II) and Ga(III)
halides, and gallium metal under identical conditions to its
reaction with ‘‘GaI’’ for purposes of comparison. The out-
comes of these reactions are highlighted in Table 2 and show
that no reaction occurs with gallium metal or gallium(III)
halides, suggesting the formation of 1a involves a reduction
process. This is perhaps confirmed by the reaction with the
gallium(II) halide, a milder reducing agent than ‘‘GaI’’, which
only affords a very low yield of 1a. Similarly, no reaction
occurred between 1 and InI, even under reflux conditions,
which is consistent with our previous studies that point
towards this being a milder reductant than ‘‘GaI’’.8,9 Further-
more, when 1 was reacted with only two equivalents of ‘‘GaI’’,
a reduced yield of 1a was obtained and much of 1 remained
unreacted. If the proposed mixed oxidation state formulation
of ‘‘GaI’’ is correct, these results suggest that its Ga(I) cations
are the active components of the salt. Finally, all attempts at in
situ cross condensation reactions, for example between 1 and 2
or between 1 and ketones, were not successful and yielded only
1 and 4, or intractable mixtures of products.
Compounds 1a–3a were characterised by X-ray crystallo-
graphy and the molecular structures of one enantiomer of each
are depicted in Fig. 1. These were used to assign the stereo-
chemistry of the products. To confirm that the crystals chosen
for the X-ray experiments represented the bulk materials, their
1H NMR spectra were obtained and these were found to be
Table 2 Comparisons between the reactions of 1 with ‘‘GaI’’ and those with other gallium and indium reagents
Substrate
Reagent
4 ‘GaI’
Products (yield)a
4 Ga2Cl4(dioxane)2
2 ‘GaI’
GaCl3
GaI3
4 Ga metal
4 InI
No reaction
No reaction
No reaction
No reaction
a
All reactions were carried out under the conditions to prepare 1a.
ꢀc
This journal is the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2007
New J. Chem., 2007, 31, 127–134 | 129

View Article Online
Fig. 1 Molecular structures of (a) 1a, (b) 2a and (c) 3a (25% thermal ellipsoids are shown).
identical to the total crystallised product. Each compound
exhibits hydrogen bonding interactions between its ketone and
alcohol functionalities, though the differences in the stereo-
chemistries of the products mean that in 1a these interactions
are intermolecular, leading to 1-dimensional hydrogen bonded
polymers, whereas in 2a and 3a they are intramolecular.
would therefore be in competition with the aldol condensation
that ultimately gives 7, thus leading to the observed mixture of
7 and 8. The apparent facile solvent quenching of the inter-
mediate gallium enolate contrasts with work involving the
reaction of GaMenI3Àn with 6 which led to room temperature
stable gallium enolates that underwent successful aldol reac-
tions with carbonyl compounds and imines.15
In order to ascertain if the Ga(I) component of ‘‘GaI’’ plays
the active role in the formation of 7, compound 6 was reacted
with Ga(II) and Ga(III) halides under identical conditions. In
these cases GaCl3 was largely unreactive, whilst treatment of 6
with Ga2Cl4(dioxane)2 almost exclusively gave the ketone, 8
(Table 3).
(ii) Reactivity of ‘‘GaI’’ towards a-halo ketones
Considering that halides are better leaving groups than alkoxy
substituents, it was thought that the reaction of a-halo ketones
with ‘‘GaI’’ might lead to g-halo b-hydroxy ketones (cf. the
reactions that gave 1a–3a). Saying this, reactions of a-halo
ketones with reducing agents such as SmI2 are known to
facilely effect halide elimination and ketone formation.10 In
the case of the reaction of the a-bromo ketone, 6, with ‘‘GaI’’,
this did occur to give the ketone, 8, as the major product,
though a significant amount of the known diketone, 7, was
also formed as a mixture of diastereoisomers (Table 3). We
believe the mechanism of formation of 7 is similar to that
reported for its synthesis from the reaction of 6 with
MeMgBr.14 That is, the reaction proceeds through a dehalo-
genation step, to yield a gallium enolate which then attacks a
second molecule of 6, leading to bromide elimination and a
concomitant 1,2-phenyl migration yielding 7 (Scheme 2). This
phenyl migration helps to explain the lack of diastereoselec-
tivity in the reaction.
As the chloride group is a poorer leaving group than
bromide, but a better leaving group than alkoxides, the
reaction of an a-chloro ketone, 9, with four equivalents of
‘‘GaI’’ in toluene was carried out for purposes of comparison.
This led to a completely different outcome to the reactions
with 1–3 and 7, namely para-alkylation of the toluene solvent
to give a low to moderate yield of the known ketone, 10.16 The
previously observed quenched enolate, 4, was formed as the
major product. The formation of 4 is not surprising in light of
the fact that 9 is known to form enolates with other reducing
agents, e.g. barium metal,17 but the absence of any coupled
products (cf. 7) is unusual. More surprising is the apparent
role of ‘‘GaI’’, or one of its disproportionation products, as a
Friedel–Crafts alkylation reagent in the formation of 10,
which was not observed in any previous reaction. Evidence
for this proposal comes from the results of the reactions of 9
with the classical Friedel–Crafts alkylation reagents, AlCl3 or
GaCl3, which gave high or quantitative yields, respectively, of
An 1H NMR spectroscopic analysis of the reaction mixture
prior to aqueous work-up revealed the presence of both 7 and
8, suggesting that the intermediate gallium enolate readily
abstracts a proton from the toluene solvent. This process
ꢀc
This journal is the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2007
130 | New J. Chem., 2007, 31, 127–134

View Article Online
Table 3 A comparison of the reactivity of ‘GaI’ and other group 13 halides towards a-halo ketones
Substrate
Reagents
4 ‘GaI’
Products (yield)
GaCl3
4 Ga2Cl4(dioxane)2
4 ‘GaI’
GaCl3
AlCl3
—
10. Of course, no evidence for 4 was seen in these reactions due
to the non-reducing nature of the salts involved. The X-ray
crystal structure of 10 was determined and its ORTEP dia-
gram is included in the supplementary material.
toluene. This seems unusual, given the strongly reducing
nature of ‘‘GaI’’ which one might think would lend it to the
formation of 4, or dihydrobenzoin, PhC(OH)C(OH)Ph, in this
reaction.
In order to shed light on the nature of the inorganic
intermediate in the reaction that gave 12, the reaction was
worked up prior to aqueous quench, affording a high yield of
the novel trimetallic, bis(enediolato) complex, 13. Presumably,
this forms by a combination of diketone reduction and ‘‘GaI’’
disproportionation processes. The molecular structure of 13 is
depicted in Fig. 2. Surprisingly, this represents the first struc-
tural characterisation of a gallium enediolato complex. It
possess three Ga(III) centres, two of which, Ga(2) and Ga(3),
have distorted tetrahedral geometries and bridge an O-centre
from each diolate ligand. The other gallium, Ga(1), has a
(iii) Reactivity of ‘‘GaI’’ towards other a-functionalised
ketones
Low oxidation state metal complexes are well known to reduce
1,2-diketones to give chelated enediolate complexes.18 To
examine the applicability of ‘‘GaI’’ to such reactions, it was
treated with benzil, 11, in toluene. After aqueous work-up,
benzoin, 12, was recovered in near quantitative yield (Scheme
3). Despite the reactivity of a-alkoxy ketones towards ‘‘GaI’’,
12 was found to be completely unreactive to this reagent in
Scheme 2 Proposed mechanism for the formation of 7. (i) ‘‘GaI’’, toluene; (ii) 6; (iii) ÀGaIBr2, 1,2-phenyl migration.
ꢀc
This journal is the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2007
New J. Chem., 2007, 31, 127–134 | 131

View Article Online
Conclusions
In summary, the reactivity of ‘‘GaI’’ towards a range of
a-functionalised ketones has been examined for the first time.
Of most interest are the reactions of this reagent with a-alkoxy
ketones which led to diastereoselective aldol coupling reac-
tions and the formation of novel trifunctional products con-
taining three contiguous stereocentres. The differences in the
stereoselectivities of these reactions has been explained by
invoking the involvement of two different transition states
that depend upon the steric bulk of the alkoxy substituent. An
aldol-type coupling reaction was also observed in the reaction
of an a-bromo ketone with ‘‘GaI’’, whilst in the reaction with a
a-chloro ketone, the gallium reagent appeared to act as a
Friedel–Crafts alkylation reagent. A selective, high yielding
reduction of a 1,2-diketone to an a-hydroxy ketone has been
achieved and the inorganic reaction intermediate structurally
characterised. Throughout this work ‘‘GaI’’ has proved to be a
stronger reducing agent than InI and has showed different
chemistry to either Ga(II) or Ga(III) salts. The results of this
study establish easy to prepare ‘‘GaI’’ as a potential specialist
C–C bond forming reagent for the organic synthetic chemist.
Work is ongoing in our laboratory to optimise the reported
reactions and to explore new synthetic avenues for ‘‘GaI’’,
especially with regard to cross coupling reactions.
Scheme 3 (i) ‘‘GaI’’, toluene; (ii) quench.
distorted square based pyramidal geometry and is coordinated
to all four O-centres. Although there are differences in the
Ga–O and Ga–I bond lengths within the structure, all lie
within the normal ranges19 and are unremarkable.
In keeping with the theme of this study, the reduction of a
series of a,b-unsaturated ketones and related compounds with
‘‘GaI’’ was attempted. In all cases, no reduction products were
returned, but in reactions with esters, deposition of gallium
metal was observed. It is thought that this arises from a
disproportionation of the gallium reagent to the metal and
GaI3 upon coordination by the O-centres of the ester. Such
disproportionation reactions have been previously reported
for ‘‘GaI’’.6a Indeed, in its reaction with trans-ethyl cinnamate
in this study, a high yield of its GaI3 adduct, [GaI3{OC
(OEt)C(H)C(H)Ph}] 14, was isolated and structurally charac-
terised. Details of this structure can be found in the supple-
mentary material.
Experimental section
General considerations
All manipulations were carried out using standard Schlenk
and glove-box techniques under an atmosphere of high purity
argon. The solvents toluene and hexane were distilled over
potassium whilst diethyl ether was distilled over Na–K alloy.
1H and 13C NMR spectra were recorded on either a Bruker
DXP400 spectrometer operating at 400.13 and 100 MHz,
respectively or a JEOL Eclipse 300 spectrometer operating at
300.52 and 75.57 MHz, respectively. Spectra were referenced
to either the 13C or residual 1H resonances of the solvent used.
High resolution mass spectra were obtained from the EPSRC
National Mass Spectrometric Service at Swansea University.
IR spectra were recorded as Nujol mulls between NaCl plates.
Melting points were determined in sealed glass capillaries
under argon and are uncorrected. ‘GaI’,6 InI20 and Ga2Cl4
(dioxane2)21 were synthesised by literature methods. All other
reagents were obtained commercially and used as received.
Fig. 2 Molecular structure of 13 (25% thermal ellipsoids are shown).
Selected bond lengths (A) and angles (1): I(1)–Ga(1) 2.4465(9), Ga(1)–
O(3) 1.930(4), Ga(1)–O(2) 1.936(4), Ga(1)–O(1) 1.984(3), Ga(1)–O(4)
1.998(3), O(1)–C(1) 1.406(6), O(1)–Ga(3) 1.930(4), I(2)–Ga(2)
2.4618(10), Ga(2)–O(2) 1.913(4), Ga(2)–O(4) 1.943(3), Ga(2)–I(3)
2.4710(9), Ga(3)–O(3) 1.940(3), Ga(3)–I(4) 2.4617(8), Ga(3)–I(5)
2.4686(8), O(3)–Ga(1)–O(2) 123.00(16), O(3)–Ga(1)–O(1) 78.07(15),
O(2)–Ga(1)–O(1) 81.27(15), O(3)–Ga(1)–O(4) 82.40(14), O(2)–Ga(1)–
O(4) 78.84(14), O(1)–Ga(1)–O(4) 137.98(15), O(3)–Ga(1)–I(1)
123.29(11), O(2)–Ga(1)–I(1) 113.71(12), O(1)–Ga(1)–I(1) 112.27(11),
O(4)–Ga(1)–I(1) 109.59(11), O(2)–Ga(2)–O(4) 80.78(15), O(2)–Ga(2)–
I(2) 108.59(12), O(4)–Ga(2)–I(2) 110.09(11), O(2)–Ga(2)–I(3)
116.27(12), O(4)–Ga(2)–I(3) 112.41(11), I(2)–Ga(2)–I(3) 121.45(4),
O(1)–Ga(3)–O(3) 79.15(15), O(1)–Ga(3)–I(4) 112.23(11), O(3)–Ga(3)–
I(4) 113.93(11), O(1)–Ga(3)–I(5) 110.05(11), O(3)–Ga(3)–I(5) 111.18(11),
I(4)–Ga(3)–I(5) 122.21(4).
General procedure for reactions involving ‘‘GaI’’. To a sus-
pension of ‘‘GaI’’ (8 mmol) in toluene (20 cm3) at À78 1C was
added a solution of the organic substrate (2 mmol) in toluene
(10 cm3) over 5 minutes. The resulting suspension was slowly
warmed to 20 1C and stirred for 24 h. Degassed HCl (1 M,
50 cm3) was then added to the resulting suspension with
vigorous shaking under an argon atmosphere. NaOH (1 M)
was added to the mixture until pH 10 was reached. The organic
layer was separated, dried over anhydrous magnesium sulfate,
and the solvent removed by rotary evaporation to afford a
crude product mixture. The composition of the product mix-
1
tures were determined by H NMR and GC/MS analyses.
ꢀc
This journal is the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2007
132 | New J. Chem., 2007, 31, 127–134

View Article Online
Table 4 Crystal data for compounds 1a–3a, 10, 13 and 14a
Compound
1a
2a
3a
10
13
14
Empirical formula
FW
Temp./K
Crystal system
Space group
a/A
b/A
c/A
C29H26O3
422.50
150(2)
Monoclinic
C2
32.142(6)
6.2276(12)
11.413(2)
90
101.70(3)
90
2237.1(8)
4
1.254
C30H28O3
436.52
150(2)
Orthorhombic
P212121
6.0010(12)
18.790(4)
20.595(4)
90
90
90
2322.3(8)
4
1.249
C31H30O3
450.55
150(2)
Monoclinic
P21/n
20.793(4)
6.1220(12)
20.961(4)
90
114.24(3)
90
C21H18
286.35
150(2)
Triclinic
ꢀ
P1
5.7983(12)
9.0444(18)
15.820(3)
94.69(3)
100.00(3)
106.81(3)
774.4(3)
2
O
C28H20Ga3I5O4
1264.10
150(2)
Monoclinic
P21/n
9.0898(18)
19.066(4)
20.516(4)
90
95.84(3)
90
C11H12GaI3O2
626.63
150(2)
Monoclinic
P21/n
7.4458(15)
18.197(4)
12.271(3)
90
94.13(3)
90
a/1
b/1
g /1
Vol./A3
2433.0(8)
4
1.230
3537.1(12)
4
2.374
1658.3(6)
4
2.510
Z
Density (calc.)/Mg mÀ3
m(Mo-Ka)
)
1.228
/mmÀ1
F(000)
0.080
896
0.079
928
0.078
960
0.074
304
6.663
2312
7.233
1136
No. of reflections collected
No. of independent reflns
Rint
5064
3292
0.1064
R1 = 0.0876
wR2 = 0.1387
13489
4205
0.0683
R1 = 0.0500
wR2 = 0.0901
7991
4444
0.0710
R1 = 0.0554
wR2 = 0.1081
4993
2689
0.0381
R1 = 0.0594
wR2 = 0.1280
15044
7690
0.0420
R1 = 0.0399
wR2 = 0.0878
4253
2849
0.0499
R1 = 0.0533
wR2 = 0.1217
Final R indices [I 4 2s(I)]
a
CCDC 626737–626742. For crystallographic data in CIF or other electronic format see DOI: 10.1039/b613669a
3
3
NB: an identical procedure was used for the reactions in
Tables 2 and 3 that employed other inorganic reagents.
(d, JHH = 6.12 Hz, 3H, CH3), 3.24 (sept, JHH = 6.12 Hz,
1H, CH(CH3)2), 4.83 (s, 1H, CH), 5.15 (s, 1H, CH), 7.23–8.12
(m, 20H, ArH); 13C NMR (100 MHz, CDCl3, 298 K): d 19.1
(CH3), 22.8 (CH3), 56.3 (CH), 68.3 (CH(CH3)2), 83.7 (COH),
86.7 (CCO), 126.2, 126.7, 126.9, 127.1, 127.8, 128.2, 128.5, 128.8,
128.9, 130.3, 130.9, 133.1, 134.8, 136.2, 137.3, 141.3 (Ar–C),
201.1 (CO); IR n/cmÀ1 (Nujol): 3345 (br., OH), 1651 (m, CQO);
HRMS: (ES) calcd for [MH+]: 451.2268; found 451.2276.
R,S,R/S,R,S-PhC(O)C(H)(Ph)C(OH)(Ph)C(H)(OMe)Ph 1a.
Following the general procedure, the resulting crude yellow
solid was recrystallised from methanol yielding colourless crys-
tals of 1a (78%): Mp 117–118 1C; 1H NMR (400 MHz, CDCl3,
298 K): d/ppm 2.92 (s, 3H, CH3), 3.37 (s, 1H, OH), 4.84 (s, 1H,
CH), 5.50 (s, 1H, CH), 6.89–7.97 (m, 20H, ArH); 13C NMR (75
MHz, CDCl3, 298 K): d 31.0 (CH3), 57.0 (COMe), 82.0 (COH),
87.2 (CCO) 126.9, 127.2, 127.3, 127.6, 127.7, 128.1, 128.5, 128.7,
128.9, 129.1, 130.7, 132.8, 134.9, 136.5, 137.5, 142.2 (Ar–C),
200.17 (CO); IR n/cmÀ1 (Nujol): 3520 (br., OH), 1681 (s, CQO);
HRMS: (ES) calcd. for [M+ + Na]: 445.1774; found 445.1775.
PhC(O)C(H)(Me)C(O)C(Me)Ph 7. Following the general
procedure, the resulting crude yellow solid was chromato-
graphed using hexane–diethyl ether (10 : 1) as an eluent.
Fractions containing 7 were dried in vacuo and the residue
recrystallised from methanol to yield colourless crystals of 7
(31%). Spectroscopic data for this compound were identical to
those previously reported.14
R,R,S/S,S,R-PhC(O)C(H)(Ph)C(OH)(Ph)C(H)(OEt)Ph 2a.
Following the general procedure, the resulting crude yellow
solid was recrystallised from methanol yielding colourless
PhC(O)C(H)(p-MeC6H4)Ph 10. Following the general pro-
cedure, the resulting crude yellow solid was chromatographed
using hexane–diethyl ether (10 : 1) as an eluent. Fractions
containing 10 were dried in vacuo and the residue recrystallised
from methanol to yield colourless crystals of 10 (24%).
Spectroscopic data for this compound were identical to those
previously reported.16
1
crystals of 2a (35%): mp 132–134 1C; H NMR (400 MHz,
CDCl3, 298 K): d/ppm 0.51 (t, 3JHH = 7.0 Hz, 3H, CH3), 2.97
(dq, 2JHH = 9.3 Hz, 3JHH = 7.0 Hz, 1H, diastereotopic CH2),
2
3
3.16 (dq, JHH = 9.3 Hz, JHH = 7.0 Hz, 1H, diastereotopic
CH2), 3.42 (s, 1H, OH), 4.63 (s, 1H, CH), 5.23 (s, 1H, CH),
6.85–8.11 (m, 20H, ArH); 13C NMR (100 MHz, CDCl3, 298
K): d 14.2 (CH3), 56.0 (CHOEt), 64.9 (CH2), 83.7 (COH), 89.8
(CCO), 126.3, 126.7, 126.9, 127.1, 127.8, 128.5, 128.6, 128.7,
129.4, 129.8, 130.3, 133.1, 134.8, 137.0, 137.4, 141.5 (Ar–C),
201.3 (CO); IR n/cmÀ1 (Nujol): 3480 (br., OH),1689 (m,
CQO); HRMS: (ES) calcd for [MH+]: 437.2111; found
437.2110.
[Ga3I5{PhC(O)C(O)Ph}2] 13. Following the general proce-
dure, the reaction mixture was filtered rather than undergoing
aqueous work-up, yielding an orange brown solution. Con-
centration of the filtrate and placement at À30 1C overnight
yielded colourless crystals of 13 (81%) Mp 163–165 1C (dec.).
1H NMR (400 MHz, CDCl3, 298 K): d 6.56–7.30 (m, 20H,
ArH); 13C NMR (75 MHz, CDCl3, 298 K): d 128.8, 129.8,
131.1, 131.8, 135.9, 136.6 (Ar–C), 139.2 (COGa); IR n/cmÀ1
(Nujol) 1616 (m, CQO); HRMS: (EI) calcd for [C28H20O4-
Ga3127I5+]: 1261.4347; found 1261.4338; Anal. calcd for
C28H20O4Ga3I5: C 26.60, H 1.59; Found: C 27.34, H 1.72.
R,R,S/S,S,R-PhC(O)C(H)(Ph)C(OH)(Ph)C(H)(OiPr)Ph 3a.
Following the general procedure, the resulting crude yellow
solid was recrystallised from methanol yielding colourless crys-
1
tals of 3a (18%): mp 162–1631C; H NMR (400 MHz, CDCl3,
3
298 K): d/ppm 0.59 (d, JHH = 6.12 Hz, 3H, CH3), 0.72
ꢀc
This journal is the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2007
New J. Chem., 2007, 31, 127–134 | 133

View Article Online
[GaI3{trans-(EtO)C(O)C(H)C(H)Ph] 14. Following the gen-
eral procedure, the reaction mixture was filtered rather than
undergoing aqueous work-up, yielding an orange brown solu-
tion. Concentration of the filtrate and placement at À30 1C
overnight yielded colourless crystals of 14 (86%) Mp 113–
Tetrahedron, 2004, 60, 1959; (c) M. R. Pitts, J. R. Harrison and C.
J. Moody, J. Chem. Soc., Perkin Trans. 1, 2001, 955; (d) K. K.
Chauhan and C. G. Frost, J. Chem. Soc., Perkin Trans. 1, 2000,
3015; (e) B. C. Ranu, Eur. J. Org. Chem., 2000, 2347; (f) C.-J. Li
and T.-H. Chan, Tetrahedron, 1999, 55, 11149; (g) P. Cintas,
Synlett, 1995, 1087 and references therein.
2 ‘‘Main Group Metals in Organic Synthesis’’, ed. H. Yamamota and
K. Oshima, Wiley-VCH, Weinheim, 2004.
3 See for example (a) R. Amemiya and R. Yamaguchi, Eur. J. Org.
Chem., 2005, 24, 5145; (b) R. M. Kellog and B. V. Syncom,
Chemtracts, 2003, 16, 79 and references therein.
4 (a) Y. Hashimoto, K. Hirata, H. Kagoshima, N. Kihara, M.
Hasegawa and K. Saigo, Tetrahedron, 1993, 49, 5969; (b) Y.
Hashimoto, K. Hirata, N. Kihara, M. Hasegawa and K. Saigo,
Tetrahedron Lett., 1992, 33, 6351.
5 R. J. Baker and C. Jones, Coord. Chem. Rev., 2005, 149, 1857 and
references therein.
6 (a) R. J. Baker and C. Jones, Dalton Trans., 2005, 1341; (b) M. L.
H. Green, P. Mountford, G. J. Smout and S. R. Peel, Polyhedron,
1990, 9, 2763 and references therein.
115 1C; 1H NMR (400 MHz, CDCl3, 298 K): d 0.50 (t, 3JHH
=
3
7.12 Hz, 3H, CH3), 3.49 (q, JHH = 7.12 Hz, 2H, CH2), 6.89
3
3
(d, JHH = 15.8 Hz, 1H, CH), 7.43 (d, JHH = 15.8 Hz, 1H,
CH), 6.66–7.05 (m, 5H, ArH); 13C NMR (75 MHz, CDCl3,
298 K): d 13.1 (CH3), 66.7 (CH2), 113.4 (CH), 152.9 (CH),
129.2, 129.3, 132.5, 132.7 (Ar–C), 174.4 (CO); IR n/cmÀ1
(Nujol): 1623 (m, CO); HRMS (EI) calcd for [M+-I]:
498.8177, found 498.8177; Anal. calcd for C11H12O2GaI3: C
21.08, H 1.93; Found: C 21.19, H, 1.95.
X-Ray crystallography
7 S. Coban, Diplomarbeit, Universitat Karlsruhe, 1999.
¨
Crystals of 1a–3a, 10, 13 and 14 suitable for X-ray structural
determination were mounted in silicone oil. Crystallographic
measurements were made using a Nonius Kappa CCD dif-
fractometer. The structures were solved by direct methods and
refined on F2 by full matrix least squares (SHELX-97)22 using
all unique data. All non-hydrogen atoms are anisotropic with
H-atoms included in calculated positions (riding model).
Compounds 1a and 2a crystallised in chiral space groups but
their X-ray analyses only established the relative stereochem-
istry of these ‘‘all light atom’’ structures. Compounds 3a and
10 crystallised in centrosymmetric space groups and are
racemic. Crystal data, details of data collections and refine-
ment are given in Table 4.
8 R. J. Baker and C. Jones, Chem. Commun., 2003, 390.
9 R. J. Baker, C. Jones, M. Kloth and D. P. Mills, New J. Chem.,
2004, 28, 207.
10 G. A. Molander and G. Hahn, J. Org. Chem., 1986, 51, 1135.
11 Chemistry of Aluminium Gallium Indium and Thallium, ed. A.J.
Downs, Blackie Academic Press, Glasgow, 1993.
12 M. Yasuda, K. Okamoto, T. Sako and A. Baba, Chem. Commun.,
2001, 157.
13 (a) S. A. Babu, M. Yasuda, I. Shibata and A. Baba, J. Org. Chem.,
2005, 70, 10408; (b) S. A. Babu, M. Yasuda, Y. Okabe, I. Shibata
and A. Baba, Org. Lett., 2006, 14, 3029.
14 R. Nouri-Bimorghi, Bull. Soc. Chim. Fr., 1969, 8, 2812.
15 Y. Han and Y.-Z. Huang, Tetrahedron Lett., 1998, 39, 7751.
16 L. Zhou and Y. Zhang, Tetrahedron, 2000, 56, 2953.
17 A. Yanagisawa, H. Takahashi and T. Arai, Chem. Commun., 2004,
580.
18 See, for example: (a) L.-C. Song, P.-C. Liu, C. Han and Q.-M. Hu,
J. Organomet. Chem., 2002, 648, 119; (b) C. S. Weinert, A. E.
Fenwick, P. E. Fanwick and I. P. Rothwell, Dalton Trans., 2003,
532; (c) J. Barrau, G. Rima and T. E. Amraoui, Organometallics,
1998, 17, 607.
19 As determined by a survey of the Cambridge Crystallographic
Database, August, 2006.
20 Synthetic Methods of Organometallic and Inorganic Chemistry, ed.
W. A. Herrmann and G. Brauer, Thieme, Stuttgart, 1996, vol. 2,
pp. 118.
Acknowledgements
We thank the EPSRC (partial studentships for S. P. G. and
R. P. R.) for financial support. The EPSRC Mass Spectro-
metry Service at Swansea University is also thanked. Dr. Mark
Bagley (Cardiff University) is thanked for helpful discussions.
21 P. Wei, X. Li and G. H. Robinson, Chem. Commun., 1999,
1287.
22 G. M. Sheldrick, SHELXL-97, Program for refinement of crystal
References
1 See for example (a) T.-P. Loh and G.-L. Chua, Chem. Commun.,
2006, 2739; (b) V. Nair, S. Ros, C. N. Jayan and B. S. Pillai,
structures, University of Gottingen, Germany, 1997.
¨
ꢀc
This journal is the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2007
134 | New J. Chem., 2007, 31, 127–134