Optimisation of a lithium magnesiate for use in the non-cryogenic asymmetric deprotonation of prochiral ketones

Article abstract of DOI:10.1039/c3dt52577e

A study has been conducted to determine whether lithium magnesiates are feasible candidates for the enantioselective deprotonation of 4-alkylcyclohexanones. The commercially available chiral amine (+)-bis[(R)-1-phenylethyl]amine (2-H) was utilised to indu

Full text of DOI:10.1039/c3dt52577e

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Optimisation of a lithium magnesiate for use in the
non-cryogenic asymmetric deprotonation of
prochiral ketones†
Cite this: Dalton Trans., 2014, 43,
1408
Javier Francos, Silvia Zaragoza-Calero and Charles T. O’Hara*
A study has been conducted to determine whether lithium magnesiates are feasible candidates for the
enantioselective deprotonation of 4-alkylcyclohexanones. The commercially available chiral amine (+)-bis-
[
(R)-1-phenylethyl]amine (2-H) was utilised to induce enantioselection. When transformed to its lithium
n
salt and combined with Bu
2
Mg, improved enantioselective deprotonation of 4-tert-butylcyclohexanone
(
with respect to the monometallic lithium amide) at 20 °C was observed. In an attempt to optimise the
reaction further, different additives were added to the lithium amide. The best performing deprotona-
tions at 0 °C were those in which (Me SiCH Mg (er pro-S 74 : 26) and (Me SiCH Mn (er pro-S 72 : 28)
were added, hence the lithium magnesiate “LiMg(2)(CH SiMe ” was used in the remainder of the
study. The optimum solvent for the reaction was found to be THF. NMR spectroscopic studies of a D -THF
solution of “LiMg(2)(CH SiMe ” appear to show that this mono-amide bis-alkyl species is in equilibrium
3
2
)
2
3
2 2
)
2
3 2
)
8
2
3 2
)
with a bis-amide mono-alkyl compound (and a tris-alkyl lithium magnesiate). When a genuine bis-amide
lithium magnesiate solution is used, the deprotonation results were essentially identical to those
Received 18th September 2013,
Accepted 1st November 2013
2 3
obtained for “LiMg(2)(CH SiMe )
2
”. By adding LiCl to “LiMg(2)(CH
SiMe )
2 3 2
” the er at 0 °C improved to
DOI: 10.1039/c3dt52577e
8
1 : 19. At −78 °C good yields and an er of 93 : 7 were obtained. This LiCl-containing base was used to
www.rsc.org/dalton
successfully deprotonate other 4-alkylcyclohexanones.
2
£
250 000 per year per batch tonne process. Therefore one
Introduction
priority in modern day synthesis is to provide solutions to this
One of the most fundamentally important reactions in problem by designing new metallating reagents that are
modern day synthesis is metallation, that is the replacement of capable of producing excellent results akin to their lithium
a relatively unreactive C–H bond with a more reactive (more counterparts but at temperatures closer to ambient. Over the
1
useful) C–metal one. Over the past 60 years, the reagents of past decade the concept of ate chemistry in synthesis has come
3
choice to carry out such reactions have generally been from to the fore. When an alkali metal organometallic reagent is
the organolithium family, primarily due to their high Brønsted combined with a magnesium one, the new ‘synergic’ bi-
basicity. However, these reagents have their drawbacks includ- metallic entity (an alkali metal magnesiate) has often been
ing that their carbanions are often so basic that they attack shown to function as a highly efficient base at temperatures
common solvents (particularly ethers such as THF) and they approaching ambient temperature. By combining LiCl with
are frequently nucleophilic; hence they generally exhibit poor conventional Grignard (RMgX) or Hauser (R NMgX) reagents,
2
functional group tolerance. To counteract these pitfalls, lithia- Knochel has demonstrated the tremendous scope achievable
tions are mostly performed at sub-ambient temperatures when these new turbo reagents are used in a multitude of
3
c,4
(often approaching −100 °C), proving a massive financial deprotonations.
Mongin has utilised lithium tri(n-butyl)-
burden for the chemical industry. Kerr has recently stated that magnesiate to regioselectively metallate an array of substrates,
by carrying out metallations at temperatures below −40 °C, the including thiophenes, fluoroaromatics, oxazoles, chloropyri-
5
additional energetic cost to industry is in the region of dines at temperatures close to ambient temperature. The sub-
sequent metallo-intermediate can undergo electrophilic
quenching to generate substituted derivatives. In special cases,
unique reactivity, including multideprotonations and unprece-
WestCHEM, University of Strathclyde, Department of Pure and Applied Chemistry,
2
95 Cathedral Street, Glasgow, G1 1XL, UK. E-mail: charlie.ohara@strath.ac.uk;
Tel: +44 (0)141 548 2667
Electronic supplementary information (ESI) available: Full experimental pro-
cedures, and NMR data. See DOI: 10.1039/c3dt52577e
dented regiochemistries with respect to ‘normal’ lithium
6
reagents can also be achieved. Until recently, the domain of
†
ate reagents has been essentially confined to achiral anions.
1408 | Dalton Trans., 2014, 43, 1408–1412
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Gros has shown that the use of chiral magnesiates specifically Table 2 Outcome of adding different metal reagents to chiral lithium
amides in the asymmetric deprotonation of 4-tert-butylcyclohexanone
a
at 0 °C for 1 hour
heteroleptic lithium magnesium alkyl TADDOLates, can
induce good levels of enantioselection, most recently in the
enantioselective addition of chiral pyrazyl magnesiate inter-
mediates across aldehydes.
b
b
Entry
Metal reagent added to 2-Li
Yield (%)
er (S : R)
7
1
2
—
76
0
4
60 : 40
—
—
MgBr
CoBr
ZnCl
2
a
3
2
a
4
2
25
83
96
99
98
89
78
99
65 : 35
70 : 30
74 : 26
58 : 42
60 : 40
64 : 36
60 : 40
72 : 28
n
Bu
(Me
Me
2
Mg
SiCH
Zn
Bu Zn
Results and discussion
3
2
)
2
Mg
Mn
2
t
Previous foundation work from our group has focused on
determining the structures (both in solution and as solids) of
magnesiates (and zincates) that incorporate chiral donor
ligands [such as (−)-sparteine and (R,R)-TMCDA] or the chiral
2
Me
Bu
3
(Me
3
Al
Al
SiCH
i
3
)
2 2
a
b
8
CoBr2 and ZnCl ; reaction time was 16 h. Determined by GC
2
amide [(R)-N-benzyl-α-methylbenzylamide]. Building on this
analysis.
foundation, here we systematically study the use of lithium
magnesiates in the enantioselective deprotonation of a class of
yardstick reagents, namely some prochiral 4-alkylcyclohexa-
we decided to use 2-Li in our subsequent reactions but altering
the second metal.
9
nones. We decided to thoroughly investigate whether lithium
magnesiates are feasible candidates for performing these metalla-
tions. The approach we chose was to co-complex a chiral lithium
amide with another additive, ultimately an organomagnesium
reagent. Firstly, we compared the performance of two commer-
cially available chiral amines (Scheme 1) [(R)-N-benzyl-
α-methylbenzylamine (1-H) and (+)-bis[(R)-1-phenylethyl]-
amine (2-H)] to generate the desired chiral lithium amide (1-Li
or 2-Li). When the respective lithium amides were utilised in
the deprotonation of 4-tert-butylcyclohexanone at ambient
temperature in THF solution, the quenched silylenol ether was
obtained in moderate yields (32 and 76% respectively) and in
At 0 °C, the additive-free reaction produced an enantio-
meric ratio (S : R) of 60 : 40 in a yield of 76%. Inorganic salts
are known to have an effect – advantageous or detrimental –
1
0
on the course of reactions. When simple inorganic salts such
as MgBr and CoBr were utilised (entries 2–4, Table 2), essen-
2
2
tially none of the desired product was formed, although
addition of ZnCl produced a yield of 25% with a S : R ratio of
5 : 35. If an organometallic reagent was added instead of the
2
6
salt, the main trend observed was that the yields improved (in
excess of 78%) although enantiomeric ratios were variable.
As the n-butyl ligand contains β-hydrogen atoms, and is
therefore prone to decomposition via a β-hydride elimination
pathway we switched our attention to the trimethylsilylmethyl
poor enantiomeric ratios (er) [(S : R); 50 : 50 and 60 : 40
n
respectively)] (entries 1 and 3, Table 1). On adding Bu
2
Mg to
−
the lithium amides, encouragingly gave vastly improved yields
95 and 83%) and most significantly enhanced er [(S : R);
5 : 35 and 70 : 30] (entries 2 and 4, Table 1). As the latter
anion (Me SiCH ). The best S : R enantiomeric ratio (74 : 26)
3
2
(
6
was obtained when the dialkylmagnesium (Me SiCH ) Mg was
3
2 2
used (entry 6, Table 2). When Zn or Al organometallics were
used (entries 7–10, Table 2) the er observed were essentially
identical to those obtained when 2-Li was utilised without an
additional metal (entry 1, Table 2). Interestingly, on adding the
transition metal alkyl (Me SiCH ) Mn to the lithium reagent,
experiment showed most promise in terms of enantioselection,
3
2 2
essentially quantitative conversion to the silyl enol ether was
observed with a high degree of enantioselection (S : R, 72 : 28;
entry 11, Table 3). Thus far our best enantioselection was
achieved using 2-Li and (Me SiCH ) Mg (entry 6, Table 3).
3
2 2
Scheme 1 Reaction of lithium chiral amides and amido (bis)alkyl
lithium magnesiates with 4-tert-butylcyclohexanone.
Table 3 Outcome of altering the 2-Li to dialkylmagnesium ratio in the
asymmetric deprotonation of 4-tert-butylcyclohexanone at 0 °C
Table 1 Outcome of reacting 1-Li and 2-Li with (or without) Bu
the deprotonation of 4-tert-butylcyclohexanone at 20 °C
2
Mg in
a
a
Entry
Metal reagent added to 2-Li
Yield (%)
er (S : R)
1
2
3
4
5
6
7
—
76
83
52
99
96
89
99
60 : 40
70 : 30
62 : 38
62 : 38
74 : 26
78 : 22
72 : 28
a
a
n
2
n
Entry
Base
Yield (%)
er (S : R)
1 equivalent Bu Mg
2 equivalents Bu
2
Mg
Mg
SiCH
2 equivalents (Me SiCH
0.5 equivalent (Me SiCH
n
1
2
3
4
1-Li
1-Li + Bu
2-Li
32
95
76
83
50 : 50
65 : 35
60 : 40
70 : 30
0.5 equivalent Bu
1 equivalent (Me
2
n
2
Mg
Mg
3
2
)
2
2
Mg
Mg
Mg
3
)
2
n
2-Li + Bu
2
3
2
)
2
a
a
Determined by GC analysis.
Determined by GC analysis.
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Therefore we focused our attention on trying to optimise this
n
reaction (and that involving commercially available Bu Mg)
2
further. By adding a deficit (0.5 equivalents) or an excess (two
n
equivalents) of Bu
2
Mg to 2-Li we discovered that the yield of
product increased for the former, but decreased for the latter,
and the enantiomeric ratio in both cases dropped to 62 : 38
(entries 2–4, Table 3). When 1 : 1, 1 : 2 and 2 : 1 ratios of 2-Li
and (Me SiCH ) Mg are utilised, the product yields are excel-
3
2 2
lent (>89%) and all the er are improved from the optimum
n
2
Bu Mg case, the best obtained was for the magnesium-rich
reaction (pro the S enantiomer, 78 : 22) although it was mod-
estly better than the 1 : 1 case (74 : 26) (entries 5–7, Table 3).
The next variable to be considered was ascertaining what
effect changing the solvent medium from THF would have on
the results. In carrying out the reaction of 2·Li and
1
2 3 2
Fig. 1 H NMR spectrum of a mixture of 2-Li and (CH SiMe ) Mg
3 2 2
8
(Me SiCH ) Mg in neat toluene, only a trace of the desired in D -THF showing that co-complexation occurs (star); however,
product formed. In diethyl ether, the GC-yield was 40% and reorganisation of ligands also takes place to give the bis(amido) mono
alkyl product (circle) and the tris-(alkyl) product (triangle).
the er was only 67 : 33 in favour of the S enantiomer. To aid
solubility in hexane, one molar equivalent of THF was added;
however, the product yield was low (23%) and the er was
6
5 : 35; hence it appears that for the systems tested THF
remains the optimum solvent choice.
At this juncture it is appropriate to detail some of the NMR
spectroscopic work that was performed in an attempt to shed
light on the active species that is likely to carry out the deprotona-
tion. Full details and spectroscopic data can be found in the
1
7
ESI.† The H (and where appropriate Li) NMR spectra of: (a) 2-H;
b) 2-Li; (c) (2-) Mg; (d) 1 : 1 2-Li and (Me SiCH Mg; and, (e)
Me SiCH Li in D -THF were compared. The NCH methylene
(
2
3
2 2
)
3
2
8
H-atom proved an important handle for comparing the spectra
1
of (a)–(d). For (a)–(c) the respective H NMR shifts were 3.50,
3
.64 and 3.84 ppm. For (d) – the active base system – two dis-
tinct resonances in approximately equal proportions were
observed (3.53 and 3.69 ppm). It was initially envisaged
1
2 3 2
Fig. 2 H NMR spectrum of a mixture 2-Li and (CH SiMe ) Mg with an
that these two resonances belonged to the diastereotopic excess of 4-H in D -THF, showing the presence of the bis(amido) mono
8
H atoms present in the organometallic complex. However, a alkyl product (star), 2-H (circle) and the generation of SiMe
DOSY NMR experiment on a D -THF solution of (d) revealed
that the solution contained two distinct amido-containing
species.† Thus we believe that the expected mono(amido)-bis- deprotonation reaction at 0 °C, an identical enantiomeric ratio
alkyl) species “LiMg(2)(CH SiMe
” undergoes ligand re- (74 : 26 pro-S) was obtained when compared to the 1 : 1 2-Li
organisation and is in equilibrium with a bis(amido)-mono- and (Me SiCH Mg reaction (Table 3, entry 5).† The key
)” and the tris(alkyl) “LiMg- finding from this experiment is that the addition of a second
” (Scheme 2 and Fig. 1). To provide evidence of equivalent of the chiral amine does not improve enantioselec-
4
(triangle).
8
(
2
3 2
)
3
2 2
)
(
(
alkyl) relative “LiMg(2)
CH SiMe
2 2 3
(CH SiMe
2
3 3
)
this equilibrium, we prepared genuine D -THF solutions of tion. This begged the question could a simple homometallic
8
“
LiMg(2)
their respective H NMR spectra corroborating that these selective deprotonation? By reacting
species were present in the initial 1 : 1 2-Li and (Me SiCH ) Mg mixture in THF with the ketone for one hour, followed by
2 2 3 2 3 3
(CH SiMe )” and “LiMg(CH SiMe ) ” and obtained alkylmagnesium chiral amide function well in this enantio-
1
n
a
1 : 1 Bu Mg–2-H
2
3
2 2
reaction (Fig. 2).
work-up, only a 3% yield of the desired silylenol ether was
Interestingly, when the bis(amido) magnesiate “LiMg- obtained. By increasing the reaction time to 16 hours, the yield
2) (CH SiMe )” was utilised in the enantioselective increased to 72% but the er was 53 : 47. Hence, for a homo-
(
2
2
3
metallic magnesium reagent to function it appears that two
amides (i.e., the absence of alkyl groups) are required
2
(
vide infra).
3 2 2
Returning to the 1 : 1 mixture of 2-Li and (Me SiCH ) Mg,
in an attempt to improve the enantioselectivity of the reaction
further, we decided to introduce some common additives
Scheme 2 Proposed equilibrium which occurs when a 1 : 1 mixture of
-Li and (Me SiCH Mg is combined in D -THF.
2
3
2
)
2
8
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Table 4 Outcome of introducing an additive to a 1 : 1 mixture of 2-Li
Table 6 Investigating the enantioselective deprotonation of several
and (Me
3
SiCH
2
)
2
Mg in the asymmetric deprotonation of 4-tert-butyl-
4-substituted-cyclohexanones using
a
1 : 1 : 1 mixture of 4-Li,
cyclohexanone at 0 °C
(Me
3
SiCH
2
)
2
Mg and LiCl at 0 °C
a
a
a
Entry
Additive
Yield (%)
er (S : R)
Entry
R
Isolated yield (%)
er (S : R)
t
1
2
3
4
—
TMEDA
LiCl
96
90
98
94
74 : 26
71 : 29
81 : 19
78 : 22
1
2
3
4
5
Bu
87
75
52
57
89
75
81 : 19
82 : 18
78 : 22
75 : 25
77 : 23
18 : 82
i
Pr
n
Pr
DMPU
Me
Ph
a
b
t
Determined by GC analysis.
6
Bu
a
b
Determined by GC analysis. Enantiomer of 4 used in this reaction.
(
(
Table 4). Focusing on the reactions involving 2-Li and
Me SiCH ) Mg, it was discovered that high yields were main-
3
2 2
To summarise, the optimal results that we have obtained
thus far are when we utilise a 1 : 1 : 1 mixture of 2-Li,
tained using additives; however, TMEDA (N,N,N′,N′-tetramethyl-
ethylenediamine) addition caused a slight drop-off in er (from
(
Me SiCH ) Mg and LiCl. As such we tested this reaction
3 2 2
7
(
7
4 : 26 to 71 : 29), but DMPU [1,3-dimethyl-3,4,5,6-tetrahydro-2-
1H)-pyrimidinone] and LiCl both enhanced selectivity (to
8 : 22 and 81 : 19 respectively). The same 81 : 19 ratio was
obtained when the LiCl was generated in situ by reaction of
·HCl with two equivalents of BuLi.
Although the primary purpose of this work was to find an
mixture with other 4-alkylcyclohexanones (Table 6). In all cases
attempted, moderate to good yields were obtained (52–89%).
The best er obtained was when the alkyl group’s steric bulk
was reduced to isopropyl, producing an er of 82 : 18. Good
n
2
n
enantioselection was also obtained for Pr, Ph and Me which
were 78 : 22, 77 : 23 and 75 : 25 respectively (Table S1†). Finally,
to ascertain whether the opposite enantioselection is possible
we employed (−)-bis[(S)-1-phenylethyl]amine in our optimum
reaction instead of its enantiomer 2. We obtained 75% isolated
yield of the compound with an S : R er of 18 : 82 at 0 °C
optimum system to operate at close to ambient temperature,
for completeness we also investigated the reaction at various
temperatures down to −78 °C (Table 5). As expected the
optimum er was obtained at the lowest temperature (93 : 7)
with an isolated yield of 87%. When compared with literature
2
(
Table 6).
work which utilised the chiral magnesium bis(amide)
(
2) ·Mg, it was noted that an identical er was obtained;
2
however, using the magnesiate system gave an increased iso-
lated yield (87% versus 66%). As alluded to earlier, in the Experimental
monometallic magnesium system two equivalents of chiral
amide are required, as one equivalent would produce an alkyl-
General methods
1
13
7
H, C NMR and Li NMR spectra were recorded on a Bruker
magnesium amide that has an inherently different reactivity
and is also subject to Schlenk-type equilibria and perhaps
oligomerisation in solution. In our magnesiate system, only
one equivalent of chiral amine is required and our sole
additive is LiCl i.e., there is no need for DMPU. A final advan-
tage is that the magnesiate reaction time is 3 hours; whereas
for the magnesium bis(amide) it is 16 hours.
1
3
DPX 400 MHz spectrometer. All C NMR spectra were proton
decoupled. Reagents were obtained from commercial suppliers
and were used without further purification unless stated
below. Purification was carried out according to standard labo-
ratory methods. Diethyl ether, tetrahydrofuran, hexane and
toluene were distilled from sodium-benzophenone. (CH
2
Si-
)-
Me Mg was prepared from the Grignard reagent (Me SiCH
3
)
2
3
2
MgCl by manipulation of the Schlenk equilibrium via the
dioxane precipitation method. The resultant off-white solid
Table 5 The effect of temperature on the enantioselective deprotona-
−
2
tion of 4-tert-butylcyclohexanone using
Me SiCH Mg and LiCl (reaction time 1 hour)
a
1 : 1 : 1 mixture of 2-Li, was purified via sublimation at 175 °C (10 Torr) to furnish
t
11
12
(
3
2
)
2
pure (CH SiMe ) Mg. Bu Zn and (CH SiMe ) Mn were pre-
2 3 2 2 2 3 2
pared according to literature methods and all synthetic work
was carried out under an inert argon atmosphere. Gas
chromatography was carried out using a Perkin Elmer Clarus
a
a
Entry
Temperature (°C)
Yield (%)
er (S : R)
b
1
2
3
4
5
6
7
8
0
−10
−20
−30
−40
−50
−60
−70
−78
−78
98 (87)
81 : 19
83 : 17
85 : 15
85 : 15
86 : 14
86 : 14
88 : 12
88 : 12
93 : 7
97
96
96
94
94
81
78
72
87
500 Gas Chromatograph.
Achiral G.C. analysis: (i) CP Chirasil-DEX CB column; (ii)
−1
carrier gas, H (45 cm s ): (i) injector/detector temperature,
2
2
50 °C; (ii) initial oven temperature, 90 °C; (iii) temperature
−1
gradient, 45 °C min ; (iv) final oven temperature, 220 °C; and
(v) detection method, FID.
9
c
10
93 : 7
Chiral G.C. analysis: (i) CP Chirasil-DEX CB column; (ii)
(45 cm s− ): (i) injector/detector temperature,
1
a
b
carrier gas, H
Determined by GC analysis. Value in parenthesis is an isolated
2
c
yield. Reaction time 3 hours.
250 °C; (ii) initial oven temperature, 70 °C; (iii) temperature
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gradient, 1.7 °C min− ; (iv) final oven temperature, 120 °C; and
(
1
Tetrahedron Lett., 2005, 46, 7989; (c) D. Catel, F. Chevallier,
F. Mongin and P. C. Gros, Eur. J. Inorg. Chem., 2012, 53.
W. Clegg, K. W. Henderson, A. R. Kennedy, R. E. Mulvey,
C. T. O’Hara, R. B. Rowlings and D. M. Tooke, Angew.
Chem., Int. Ed., 2001, 40, 3902.
v) detection method, FID.
6
7
Representative experimental procedure
To a flame-dried and Ar-purged Schlenk flask, (CH SiMe ) Mg
0.19 g, 1.0 mmol) was added and dissolved in anhydrous THF
5 mL) and the solution stirred for 5 min. BuLi (1.6 M in
hexanes, 1.0 mmol) was added and then the solution was
cooled to °C. Bis[(R)-1-phenylethyl]amine (0.22 mL,
.0 mmol) was added and the cold solution is stirred for
2
3 2
(a) G. Dayaker, D. Tilly, F. Chevallier, G. Hilmersson,
P. C. Gros and F. Mongin, Eur. J. Inorg. Chem., 2012, 6051;
(
(
(
b) O. Payen, F. Chevallier, F. Mongin and P. C. Gros, Tetra-
hedron: Asymmetry, 2012, 23, 1678; (c) D. Tilly, K. Snegaroff,
G. Dayaker, F. Chevallier, P. C. Gros and F. Mongin, Tetra-
hedron, 2012, 68, 8761.
0
1
1
1
hour. After that, 4-tert-butylcyclohexanone (1a) (152 mg,
.0 mmol) was added to the mixture, and the resulting suspen-
8
9
(a) A. R. Kennedy and C. T. O’Hara, Dalton Trans., 2008,
4975; (b) D. R. Armstrong, W. Clegg, S. H. Dale, J. Garcia-
sion was allowed to stir for 1 hour. TMSCl (0.256 mL,
.0 mmol) was added and regular sampling and analysis by
gas chromatography monitored the progress of the reaction.
After that the reaction is quenched with aq. NH Cl solution
10 mL) and extracted with AcOEt (3 × 15 mL). The combined
organic layers were dried over Na SO and concentrated
in vacuo to give a residue that was purified by combi-flash
chromatography [hexanes–Et O = 99 : 1] to afford (4-tert-butyl-
cyclohexen-1-enyloxy)trimethylsilane as
195 mg, 87%).
Alvarez, R. W. Harrington, E. Hevia, G. W. Honeyman,
A. R. Kennedy, R. E. Mulvey and C. T. O’Hara, Chem.
Commun., 2008, 187.
2
4
(a) K. Aoki, H. Noguchi, K. Tomioka and K. Koga, Tetra-
hedron Lett., 1993, 34, 5105; (b) K. Aoki and K. Koga, Chem.
Pharm. Bull., 2000, 48, 571; (c) M. J. Bassindale,
J. J. Crawford, K. W. Henderson and W. J. Kerr, Tetrahedron
Lett., 2004, 45, 4175; (d) M. Majewski, A. Ulaczyk-Lesanko
and F. Wang, Can. J. Chem., 2006, 84, 257; (e) M. Majewski
and F. Wang, Tetrahedron, 2002, 58, 4567; (f) M. Majewski,
A. Ulaczyk and F. Wang, Tetrahedron Lett., 1999, 40, 8755;
(
2
4
2
a
colourless oil
(
(
1
g) M. Majewski and P. Nowak, Tetrahedron Lett., 1998, 39,
661; (h) M. Majewski, R. Lazny and P. Nowak, Tetrahedron
Conclusions
Our ‘optimised’ lithium magnesiate appears to have the high
activity of a lithium reagent, good selectivity of a magnesium
Lett., 1995, 36, 5465; (i) C. D. Graf, C. Mulan and
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We gratefully acknowledge the support of the EPSRC
(J001872/1 and L001497/1) for the award of a Career Accelera-
tion Fellowship to CTOH.
(
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1412 | Dalton Trans., 2014, 43, 1408–1412
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