Highly effective alkaline earth catalysts for the sterically governed hydrophosphonylation of aldehydes and nonactivated ketones

Article abstract of DOI:10.1002/chem.201201489

Down-to-earth catalysis: Heteroleptic and, more interestingly, homoleptic complexes of the large alkaline earth metals (calcium, strontium, and barium) constitute remarkably efficient catalysts for hydrophosphonylation reactions of aldehydes and nonactiva

Full text of DOI:10.1002/chem.201201489

COMMUNICATION
DOI: 10.1002/chem.201201489
Highly Effective Alkaline Earth Catalysts for the Sterically Governed
Hydrophosphonylation of Aldehydes and Nonactivated Ketones
Bo Liu, Jean-FranÅois Carpentier,* and Yann Sarazin*[a]
Owing to their unusual biological activity,[1] a-hydroxy-
phosphonates and their parent a-hydroxyphosphonic acids
have found widespread applications in the biological and
pharmaceutical industries, for example, as analogues of nat-
ural phosphates,[2] antibiotic, antitumor or antiviral agents,[3]
herbicides,[4] or enzyme inhibitors.[5] Ternary and quaternary
a-hydroxyphosphonates are commonly obtained by hydro-
phosphonylation of carbonyl species, that is, by the addition
of dialkylphosphite to aldehydes or ketones.[6] This reaction
has long been known to be promoted by strong bases during
the so-called Pudovik reaction,[7] but yields are often limited
by side reactions such as retro-hydrophosphonylation[8] and
phospha-Brook rearrangement.[9] Over the past 20 years,
mono- or bimetallic complexes that are built around a lan-
thanide metal,[10] titanium,[11] or aluminum[12] have emerged
as a potent class of catalysts for the hydrophosphonylation
of aldehydes that allow for better control of this reaction.
The enantioselective hydrophosphonylation of aldehydes
and imines has even become possible due to the use of
chiral, metal-based precatalysts.[10–12]
The coordination chemistry of the large alkaline earth
metals calcium, strontium, and barium has experienced a
surge of interest over the past decade.[16] Well-defined com-
plexes of these environmentally benign metals, and of calci-
um more specifically, have demonstrated a remarkable abili-
ty as catalysts in a variety of organic transformations.[17]
Their use ranges most notably from the hydroamination[18,19]
and hydrophosphination[19c,20] of unsaturated substrates to
the hydrogenation[21] and hydrosilylation[22] of activated al-
kenes and the polymerization of styrene[23] or bioresourced
cyclic esters.[24] Heteroleptic complexes of the type
(thf)x] (Ae=Ca, Sr, Ba; (LX)À =mono-
[(LX)Ae{NACTHUNRGTENNUG(SiMe3)2}ACHTUGNTRENNUGN
anionic, multidentate ancillary ligand) that include a nitro-
gen-containing ligand, such as the ubiquitous b-diketiminate
[HC-{C(Me)2N-2,6-iPr2C6H3}2]À or an aminotropon
ACTHUNRTGNE(GNU imin)ate,
have been at the forefront of catalyst development in this
area.[18–20] Recently, phenolate ligands have also provided
Ae ring-opening polymerization catalysts that display excel-
lent performances.[24g–o] The preparation of stable, heterolep-
tic Ae complexes is intrinsically challenging because of their
infamous propensity to decompose during ligand-scrambling
reactions; however, this is often mandatory because occur-
rences of efficient, yet more readily accessed homoleptic[25]
However, success has been more elusive in the case of ke-
tones, which are less reactive because of their lower electro-
philicity. A few organocatalysts that allow for the (enantio-
selective) synthesis of quaternary a-hydroxyphosphonates
have been reported,[13] but their reaction rates are very slow.
It is only recently that Feng and co-workers have described
Ae catalysts, such as [Ae{N
remain extremely scarce. [Ca{N
A
(thf)x] (x=0, 2),
2A(thf)2] was em-
N
CHTUNGTRENNUNG
ployed by Feijen and Westerhausen et al. to promote the
polymerization of cyclic esters,[26] and Hillꢀs hydroamina-
tion[18j,19a,b] and Tischenko[27] reactions are the main achieve-
ments in the area of fine chemistry that use this precursor.
In addition, Westerhausen et al. reported that the hydro-
phosphination of alkynes and butadiynes has been mediated
the efficient hydrophosphonylation of ketones and trifluoro-
[14]
methylketones by using Lewis acids, such as TiACTHUNRGTNEUNG(OiPr)4
and Et2AlCl,[15] respectively. Earlier this year, Wang and co-
workers reported several discrete lanthanide pre-catalysts
that are supported by pyrrole-based ancillary ligands and
which proved effective for the hydrophosphonylation of
nonactivated ketones, even with a minimal loading (down to
0.1 mol%) of the catalytic metal species.[10f,g]
(thf)4] with great efficacy.[28] Despite their sim-
by [CaACHTNUGTRENNUG(PPh2)2ACHTUTGNRENNUGN
ilarities to rare-earth elements, complexes of the large Ae
metals have, to our knowledge, never been used to catalyze
hydrophosphonylation reactions.[29]
Herein, we report that the simple [Ae{NACTHNUTRGENNUG(SiMe3)2}2ACHTUNGTRENNUNG(thf)2]
[a] Dr. B. Liu, Prof. Dr. J.-F. Carpentier, Dr. Y. Sarazin
Organometallics: Materials and Catalysis
Institut des Sciences Chimiques de Rennes
UMR 6226 CNRS, Universitꢁ de Rennes 1
Campus de Beaulieu, 35042 Rennes Cedex (France)
Fax : (+33)2-23-23-69-39
complexes (Ae=Ca, Sr, Ba) constitute competent precata-
lysts for the selective hydrophosphonylation of aldehydes
and nonactivated ketones, providing full conversion of large
substrate loadings within minutes at room temperature. The
reactions with these virtually ligand-free complexes were
performed in the absence of solvent with a loading of cata-
lyst as low as 0.02 mol%. It is shown that the catalyst activi-
ty increases with the size of the metal and is largely influ-
enced by steric factors. The homoleptic Ae precatalysts are
as effective as more sophisticated heteroleptic complexes
E-mail: jean-francois.carpentier@univ-rennes1.fr
yann.sarazin@univ-rennes1.fr
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201201489; including detailed
experimental procedures and spectroscopic data for the prepared
compounds.
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tries 2, 6, and 7). The reactions
were too fast to discriminate
between the three complexes,
and we found that comparison
could not be reliably achieved
even in a diluted medium or at
higher substrate loadings. For
example, full conversion was
still
obtained
when
a
Figure 1. Alkaline earth heteroleptic [(LX1)Ae{N
[(LX3)Ca{N
(SiMe3)2}] (5) and homoleptic [Ae{N(SiMe3)2}
hydrophosphonylation of aldehydes and ketones.
G
(thf)x] (1–3), [(LX2)Ca{N
ACHTUNGTRENUGNN ACHTUNRTGEG(NNUN SiMe3)2}ACHTNUGTRENUN(GN thf)] (4), and
0.02 mol% loading of 1 was
employed (Table 1, entry 3).
Similarly, we were not able to
detect a clear influence of the
E
N
CHTUNGTRENNUNG
that are stabilized by sterically encumbered ancillary li-
gands.
nature of the metal at this stage because full conversion was
observed within 30 s with the use of Ca, Sr, or Ba complexes
1–3 (0.1 mol%, Table 1, entries 1, 4, and 5). It is worth
noting that although no reliable activity or turnover fre-
quency (TOF) figures can be quoted, the alkaline earth
complexes 1–5 compared very favorably in terms of reaction
rates with other metal-based catalysts reported to date, in-
cluding the remarkable pyrrolyl-containing lanthanide com-
plexes developed by Wang et al.[10f–g] Attempts to control
the activity of these Ae catalysts in this reaction were not
pursued, instead, reactions with the less reactive ketones
were explored.
Because heteroleptic Ae precatalysts often display higher
catalytic activity and better control than their homoleptic
counterparts, the ability of the heteroleptic complexes
[(LX1)Ae{N
N
(thf)x] (LX1H=an imino–aniline; Ae=
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
amino ether phenol; Figure 1) to catalyze the addition of di-
ethylphosphite to benzaldehyde or acetophenone at 20Æ
18C was first investigated (Table 1). To improve the overall
atom efficiency of the reaction and to reduce both organic
and metallic wastes, the reactions were performed under sol-
vent-free conditions and high substrate-to-metal ratios were
sought. When a 0.05 mol% loading of the calcium com-
plexes 1, 4, or 5 was used, the complete addition of HP(O)-
The addition of diethylphosphite to acetophenone pro-
ceeded rapidly, although in this case only partial conversion
was obtained after 60 s at room temperature by using
0.05 mol% of 1–5 (Table 1, entries 8–12). The corresponding
turnover frequencies were very high; typically, around 1100–
1400 catalytic cycles were completed per minute. The cata-
lytic activity increased slightly with the size and electroposi-
tive nature of the metal, and the corresponding trend Ca<
Sr<Ba (Table 1, entries 9–11) was in line with the observa-
tions made during the intermolecular hydroamination of ac-
tivated alkenes.[19c] However, it appeared that the metal and
the ligand framework had, at best, only a moderate influ-
ence on the activity (Table 1, entries 8–12). Interestingly, we
ACHTUNGTRENNUNG(OEt)2 to an equimolar amount of benzaldehyde was ach-
ieved extremely rapidly, typically within 20 s (Table 1, en-
Table 1. The hydrophosphonylation of benzaldehyde and acetophenone
with diethylphosphite, catalyzed by heteroleptic complexes 1–5 and
[Ca{N
ACHTUNGTRENNUNG(SiMe3)2}2ACHTUNGTRENNUNG
(thf)2] (6).[a]
observed that the homoleptic[25] complex [Ca{N
(thf)2] (6) displayed an equally high performance; the results
of the addition of HP(O)(OEt)2 to benzaldehyde or aceto-
ACHTUGNRTNE(NUNG SiMe3)2}2-
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
Entry
R
Cat.
[mol%]
Time
[s]
Conv.
[%]
TOF
[minÀ1
]
phenone (Table 1, entries 13 and 14) when catalyzed by 6
were remarkably similar to those obtained, for example,
with complex 1 (Table 1, entries 2 and 8).
G
U
1
2
3
4
5
6
7
8
9
10
11
12
13
14
H
H
H
H
H
H
H
Me
Me
Me
Me
Me
H
1 (0.1)
30
20
300
30
30
20
20
60
60
60
60
60
20
60
99[b]
>99.9[c]
99[b]
–
–
–
–
–
–
–
1220
1300
1420
1180
1100
–
1 (0.05)
1 (0.02)
2 (0.1)
The data collected in Table 2 further highlight the similar
performance of the hetero- and homoleptic Ae complexes
1–3 and 6–8.[30] In the case of the reactions with acetophe-
none (Table 2, entries 1–6), partial conversion (ca. 60–75%)
was deliberately obtained after 1 min by using 0.05 mol% of
precatalyst. For a given metal, there was little difference be-
tween the homo- and heteroleptic complexes, and the corre-
sponding TOF values were excellent, typically in the range
of 1200–1480 minÀ1. Similarly, only a minor difference be-
tween the two families of complexes was detected during
the catalyzed addition of diethylphosphite to the far less re-
active ortho-chloroacetophenone (Table 2, entries 7–12); the
homoleptic complexes 6–8 were only marginally slower (55–
99[b]
3 (0.1)
99[b]
4 (0.05)
5 (0.05)
1 (0.05)
2 (0.05)
3 (0.05)
4 (0.05)
5 (0.05)
6 (0.05)
6 (0.05)
>99.9[c]
>99.9[c]
61[c]
65[c]
71[c]
59[c]
55[c]
>99.9[c]
60[c]
Me
1200
[a] Reaction conditions: neat substrates in a 1:1 ratio (10–50 mmol),
room temperature. [b] Isolated yield. [c] Conversion was determined by
1H NMR spectroscopy.
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Alkaline Earth Catalysts for Sterically Governed Hydrophosphonylation
COMMUNICATION
Table 2. Comparison between homoleptic (6–8) and heteroleptic (1–3)
Ae catalysts in the catalyzed hydrophosphonylation reactions of aceto-
phenone and ortho-chloroacetophenone with diethylphosphite.[a]
Table 3. Hydrophosphonylation reactions of carbonyl compounds with
diethylphosphite, catalyzed by the homoleptic Ae complexes 6–8.[a]
Entry
X
R
Cat.
([mol%])
Time
Conv.[b] TOF
[%]
G
ACHTUNGTRENNUNG ]
[minÀ1
Entry
X
Cat.
([mol%])
Time
[min]
Conv.[b]
[%]
TOF
[minÀ1
]
1
2
H
H
Me 6 (0.05)
1 min
1 min
60
60
1200
1200
G
R
G
Me [Ca{N
(0.05)
A
2ACHTUNGTNER(NUNG thf)]
1
2
3
4
5
6
7
8
9
H
H
H
H
H
H
Cl
Cl
Cl
Cl
Cl
Cl
1 (0.05)
2 (0.05)
3 (0.05)
6 (0.05)
7 (0.05)
8 (0.05)
1 (0.1)
2 (0.1)
3 (0.1)
6 (0.1)
7 (0.1)
8 (0.1)
1
1
1
1
1
1
7
7
7
61
65
71
60
70
74
62
70
76
55
60
65
1220
1300
1420
1200
1400
1480
89
100
109
55
3
4
5
6
7
8
9
10
H
H
H
F
Cl
Br
Me [Ca{N
A
1 min
58
1160
93
10
85
55
Me 6 (0.1)
iPr 6 (0.1)
Me 6 (0.1)
Me 6 (0.1)
Me 6 (0.1)
10 min 93
10 min 10
10 min 85
10 min 55
20 h
48 h
48 h
4 h
1.5 min 96
1.5 min 95
1.5 min 27
1.5 min 16
3 min
3 min
3 min
1.5 h
38
0.3
–
–
1.4
NO2 Me 6 (0.1)
Me Me 6 (0.1)
OMe Me 6 (0.1)
H
Me
H
H
H
H
H
traces
traces
33
10
11
12
10
10
10
11
60
65
12[c]
13[c]
14[c]
15[c]
16[d]
17[d]
18[d]
19[d]
H
H
6 (0.1)
6 (0.1)
640
633
180
107
217
240
257
[a] Reaction conditions: neat substrates in a 1:1 ratio (10–20 mmol),
room temperature. [b] Conversion was determined by 1H NMR spectro-
scopy.
Me 6 (0.1)
Ph 6 (0.1)
Ph 6 (0.1)
Ph 7 (0.1)
Ph 8 (0.1)
Ph 6 (0.1)
65
72
77
30
Me
3.3
65% conversion within 10 min, TOF=55–65 minÀ1) than
their heteroleptic analogues 1–3 (62–76% conversion in
7 min, TOF=89–109 minÀ1). It is worth noting however,
that in this set of experiments, and as previously found, the
activity of the catalyst for a given ligand (i.e., LX1À vs. [N-
[a] Reaction conditions: neat substrates in 1:1 ratio (10–20 mmol) at
room temperature, unless otherwise specified. [b] Conversion was deter-
mined by 1H NMR spectroscopy. [c] Reactions were carried out in tol-
uene (5 mL) at À138C; 10 mmol of each substrate. [d] Reactions were
carried out in toluene (5 mL) at 08C; 10 mmol of each substrate.
ACHTUNGTRENNUNG
The role of the ortho substituent in acetophenone deriva-
tives was then probed by using a 0.1 mol% loading of 6
under solvent-free conditions (Table 3, entries 4 and 6–11).
Whereas a 93% conversion of acetophenone was achieved
within 10 min (Table 3, entry 4, TOF=93 minÀ1), the reac-
tion rate decreased slightly upon the introduction of an
ortho-fluoro substituent (Table 3, entry 6, TOF=85 minÀ1).
The reaction rate was lower again with the introduction of a
chloro substituent (Table 3, entry 7, TOF=55 minÀ1) or,
preparation of the heteroleptic complexes 1–5 and the limit-
ed gains in terms of their catalytic activity in the hydrophos-
phonylation reactions compared with the use of the homo-
leptic complexes 6–8, we opted to focus on the readily ac-
cessed [Ae{N
though it was less active in the series of homoleptic precata-
lysts than others, [Ca{N(SiMe3)2}2A(thf)2] (6) was prioritized
ACHTUNGTRENNUNG(SiMe3)2}2ACHTUNGTRENN(UGN thf)2] for further investigations. Al-
A
CHTUNGTRENNUNG
ahead of its heavier congeners on account of the fully bio-
compatible and nontoxic nature of calcium.
more dramatically, with
a bromo substituent (Table 3,
The scope of the reactions of diethylphosphite with other
ketones that have substituents of varying steric bulk and
entry 8, TOF=0.3 minÀ1). This trend indicates that the con-
version is only mildly influenced by electronic factors but,
conversely, indicates a greater role of the steric contribu-
tion.[31] The unusually stronger influence of steric over elec-
tronic factors was further substantiated when the ortho-
halide substituents were replaced by bulky groups with dif-
ferent electronic properties; the catalytic activity was essen-
tially suppressed when not only a NO2 group (Table 3,
entry 9), but also a Me (Table 3, entry 10) or OMe moiety
(Table 3, entry 11), was installed at the ortho position of ace-
tophenone.
The significant role of steric factors on the activity of the
complexes was further highlighted by tuning the size of the
carbonyl substrate (Table 3, entries 12–19). These reactions
were purposely carried out at low temperatures (À13 to
08C) and in dilute solutions to enable accurate comparisons,
rather than trying to maximize final conversions. In a com-
electronic properties were investigated with catalyst
6
(Table 3). A preliminary control experiment indicated that,
as anticipated, the identity of the amido group in the ligand-
free homoleptic catalysts[25] had no influence on the out-
come of the catalyzed addition of HP(O)
phenone. Indeed, 6 and its less bulky analogue [Ca{N-
(SiMe2H)2}2A
(thf)][24k] exhibited identical activity (compare
ACHTUNGRTEN(NUNG OEt)2 to aceto-
A
CHTUNGTRENNUNG
entries 1 and 2 in Table 3). Moreover, the role of THF mole-
cules that were coordinated to the metal center was consid-
ered negligible because 6 and its THF-free derivative [Ca{N-
ACHTUNGTRENNUNG(SiMe3)2}2] displayed equal activity (Table 3, entries 1 and 3,
TOF=1160–1200 minÀ1). The reaction was sensitive to steric
considerations; the rate was an order of magnitude lower
for isobutyrophenone (Table 3, entry 5, TOF=10 minÀ1)
than for acetophenone (Table 3, entry 4, TOF=93 minÀ1).
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J.-F. Carpentier, Y. Sarazin, and B. Liu
parison of the relatively small benzaldehyde (Table 3,
entry 12) and o-Me-benzaldehyde (Table 3, entry 13), the in-
troduction of the Me group had very little influence on the
catalytic activity, and impressive turnover frequencies of
633–640 minÀ1 were obtained even at À138C. This contrast-
ed with the earlier observation that the reaction of aceto-
phenone was completely inhibited by the introduction of the
o-Me substituent (Table 3, entries 4 and 10). It is worth
noting that, as expected, acetophenone (Table 3, entry 14,
TOF=180 minÀ1) was substantially less reactive than benz-
nation and hydrophosphination of activated alkenes.[19c]
Nevertheless, general conclusions on the relationship be-
tween size of the alkaline earth element and catalyst activity
cannot be drawn at this stage because, for instance, there is
still a large amount of evidence for the reverse reactivity
order for the catalyzed intramolecular cyclohydroamination
of aminoalkenes.[18]
Organic chemists now have a new, efficient, and conven-
ient catalytic tool at their disposal that may be able to per-
form a range of catalyzed atom-efficient reactions under
green chemistry conditions. Another promising example of
ACHTUNGTRENNUNG
aldehyde (Table 3, entry 12, TOF=640 minÀ1) under these
conditions and, accordingly, the hydrophosphonylation of
benzophenone proceeded even more slowly (Table 3,
entry 15, TOF=107 minÀ1). Even at 08C, relatively lower
turnover frequencies (although still in the remarkable range
217–257 minÀ1) were obtained for the addition of HP(O)-
an organic transformation catalyzed by [Ae{N
AHCTUNGTRENNUNG
ACHTUGNRTNE(NUNG SiMe3)2}2-
loadings (1–5 mol%) and long reaction times were required
to ensure high conversion in the Tischenko reaction.[27] We
are continuing to explore the scope of Ae-catalyzed hydro-
phosphonylation reactions, and also endeavoring to develop
an enantioselective version of this reaction by using chiral
heteroleptic precatalysts.
ACHTUNGTRENNUNG(OEt)2 to benzophenone catalyzed by 6–8 (Table 3, en-
tries 16–18), and the reactivity trend previously observed for
the metal centers (Ca<Sr<Ba) was again confirmed in the
case of benzophenone. Finally, poor conversion was ob-
tained when o-Me-benzophenone, a bulkier substrate, was
used: the Ca precatalyst 6 only achieved a 30% conversion
of the substrate after 1.5 h at 08C (Table 3, entry 19, TOF=
3.3 minÀ1).
In conclusion, we have shown for the first time that the
selective addition of dialkylphosphites to aldehydes or ke-
tones to yield tertiary or quaternary phosphonates, respec-
tively, can be effectively promoted by complexes of the
large alkaline earth metals, Ca, Sr, and Ba. Both homoleptic
and heteroleptic precatalysts can be used, and the two types
of complexes exhibit very similar performance.[30] The readi-
Experimental Section
General procedure: The relevant carbonyl compound (2–50 mmol) was
added to the alkaline earth metal complex (10 mmol) in a Schlenk flask
under an argon atmosphere, and an equimolar amount of diethylphos-
phite (2–50 mmol) was then added. The resulting mixture was stirred at
room temperature for the appropriate time. The reaction was quenched
1
by addition of MeOH. The conversion was determined by H NMR anal-
ysis of a sample collected from this mixture. The reaction mixture was
then poured into pentane, and the precipitated product was isolated after
filtration. The yields were calculated based on the weight of the isolated
pure product. When a solvent (toluene) was used to dilute the reaction
mixture, it was added to the reaction vessel immediately prior to the ad-
dition of diethylphosphite.
ly prepared (pre)catalysts [Ae{NACTHUNGTRENNGU(SiMe3)2}2ACHTUTGNREN(NGUN thf)2] allows effi-
cient and easy hydrophosphonylation reactions. Remarkably
high catalytic activity was observed, not only for the reac-
tion of benzaldehydes (full conversion was observed within
a few minutes with 0.02 mol% of catalyst at room tempera-
ture), but also, and most interestingly, for the less reactive
nonactivated ketones, for which turnover numbers as high
as 1200–1500 minÀ1 were achieved. These values are greater
by a considerable margin than those reported to date. We
found that the reaction was particularly sensitive to steric ef-
fects; for example, in the case of arylketones, the activity
dropped with an increase in size of the substituent at the
ortho position of the aromatic ring. However, the efficiency
of the catalyst was mostly unaffected when the electronic
properties of the ketones were tuned. The ability of the
system to perform well even when very low loadings of
these simple precatalysts were used, combined with the fact
that these reactions are conducted in the complete absence
of solvent, with no excess of any reagent and under mild
conditions (room temperature, short reaction times), renders
the whole system particularly environmentally friendly. For
a given type (heteroleptic or homoleptic) of Ae complex
and for all carbonyl substrates investigated, the activity of
the catalyst system always increased, to some extent, with
the size of the metal (Ca<Sr<Ba). This is consistent with
the observations made during the intermolecular hydroami-
Acknowledgements
The authors are grateful to the European Research Council for sponsor-
ship of this research (ChemCatSusDe Marie Curie FP7-PEOPLE-2010-
IIF fellowship to B.L.), and also thank the CNRS (Y.S.) and the Institut
Universitaire de France (J.-F.C.) for their support.
Keywords: aldehydes · alkaline earth metals · catalysis ·
green chemistry · hydrophosphonylation · ketones
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Alkaline Earth Catalysts for Sterically Governed Hydrophosphonylation
COMMUNICATION
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[25] We are aware that precursors of the type [Ae{NACTHUNTGRENNG(U SiMe3)2}2ACHTUNGTRENNUNG(thf)2]
(Ae=Ca, Sr, Ba) do not truly qualify as homoleptic because THF
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J.-F. Carpentier, Y. Sarazin, and B. Liu
[28] T. M. A. Al-Shboul, V. K. Pꢆlfi, L. Yu, R. Kretschmer, K. Wimmer,
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[29] Heterogeneous CaO has been used as a catalyst for the addition of
dialkylphosphites to unsaturated electrophiles, see: E. Martꢇnez-
Castro, O. Lꢃpez, I. Maya, J. G. Fernꢆndez-BolaÇos, M. Petrini,
Green Chem. 2010, 12, 1171.
molecular alkene hydroamination, in which a simple homoleptic cat-
alyst CaACHTNUGTRNEUGN(NR2)2 or, in other cases, a heteroleptic catalyst, could be
the superior, depending on the nature of the substrate; see
refs. [18a–h] and F. Buch, S. J. Harder, Z. Naturforsch 2008, 63, 169.
[31] Wang and co-workers also reported a significant decrease in activity
on changing the substituent from ortho-chloro- to ortho-bromoace-
tophenone; see refs. [10f,g].
[30] Note that for the hydrosilylation (see ref. [21]) and hydrogenation
(see ref. [22]) of alkenes, Harder and co-workers found that homo-
leptic, bisalkyl Ca catalysts are more active than heteroleptic b-dike-
timinate catalysts). More varied results were observed in the intra-
Received: April 30, 2012
Revised: July 17, 2012
Published online: && &&, 0000
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These are not the final page numbers!

Alkaline Earth Catalysts for Sterically Governed Hydrophosphonylation
COMMUNICATION
Alkaline Earth Metals
B. Liu, J.-F. Carpentier,*
Y. Sarazin* .................... &&&& — &&&&
Highly Effective Alkaline Earth Cata-
lysts for the Sterically Governed
Hydrophosphonylation of Aldehydes
and Nonactivated Ketones
Down-to-earth catalysis: Heteroleptic
and, more interestingly, homoleptic
complexes of the large alkaline earth
metals (calcium, strontium, and
catalysts for hydrophosphonylation
reactions of aldehydes and nonacti-
vated ketones (see scheme). Perfect
chemoselectivities and unprecedented
turnover frequencies are reported.
barium) constitute remarkably efficient
Chem. Eur. J. 2012, 00, 0 – 0
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These are not the final page numbers!