Ruthenium Catalyzed Selective Hydroboration of Carbonyl Compounds

Article abstract of DOI:10.1021/acs.orglett.5b02352

Using the [Ru(p-cymene)Cl₂]₂ (1) complex, catalytic hydroboration of aldehydes and ketones with pinacolborane under neat and mild conditions is reported. At rt, chemoselective hydroboration of aldehydes over the ketones is also attained. Mechanistic studies confirmed the immediate formation of monohydride bridged dinuclear complex [{(μ⁶-p-cymene)RuCl}₂(μ-H-μ-Cl)] (1b) from the reaction of 1 with pinacolborane, which catalyzed the highly efficient hydroboration reactions. The catalytic cycle containing mononuclear Ru-H species and intramolecular 1,3-hydride transfer is postulated.

Full text of DOI:10.1021/acs.orglett.5b02352

Letter
pubs.acs.org/OrgLett
Ruthenium Catalyzed Selective Hydroboration of Carbonyl
Compounds
Akash Kaithal,† Basujit Chatterjee,† and Chidambaram Gunanathan*
School of Chemical Sciences, National Institute of Science Education and Research (NISER), Bhubaneswar-751 005, India
S
* Supporting Information
ABSTRACT: Using the [Ru(p-cymene)Cl2]2 (1) complex,
catalytic hydroboration of aldehydes and ketones with pinacolbor-
ane under neat and mild conditions is reported. At rt,
chemoselective hydroboration of aldehydes over the ketones is
also attained. Mechanistic studies confirmed the immediate
formation of monohydride bridged dinuclear complex [{(η6-p-
cymene)RuCl}2(μ-H-μ-Cl)] (1b) from the reaction of 1 with pinacolborane, which catalyzed the highly efficient hydroboration
reactions. The catalytic cycle containing mononuclear Ru−H species and intramolecular 1,3-hydride transfer is postulated.
oronate esters are excellent synthetic surrogates in organic
synthesis, and an assortment of chemical transformation is
absence of any significant hydroboration of aldehydes with
pinacolborane at rt.14
B
developed to incorporate them into organic substrates.1,2 The
organoboronates are stable, nontoxic compounds and are thus
preferred over the other organometallic compounds. Thus, a
number of catalytic methods are employed for the synthesis of
alkyl and vinyl boronates.2,3 Particularly, among metal-catalyzed
reactions rhodium catalysts are extensively used in hydro-
boration.3 Use of ruthenium catalysts in hydroboration of
alkenes resulted in either mixture of products4 or provided
dehydrogenative vinyl boronates in addition to the hydro-
boration.5 Efficient conversion of carbonyl compounds into the
corresponding alcohols is an important transformation in organic
synthesis.6 Transition metal complexes of molybdenum7 and
titanium,8 and main group zinc complexes,9 are reported to
catalyze the hydroboration of carbonyl compounds.10 While
ruthenium catalyzed synthesis of organoboronates is well
explored,4,5,11 its application in hydroboration of carbonyl
compounds is limited to one interesting example, which is
based on bifunctional catalysis.12 Moreover, chemoselective
hydroboration of aldehydes over ketones is a synthetically
valuable and unknown transformation. Our interest in the
hydroboration of carbonyl compounds emanated from the
recently reported ruthenium catalyzed hydrosilylation reaction of
aldehydes.13 Herein, we report highly efficient hydroboration of
aldehydes and ketones and chemoselective hydroboration of
aldehydes under mild conditions using the [Ru(p-cymene)Cl2]2
as a precatalyst.
Further, a range of aromatic and aliphatic aldehydes were
subjected to hydroboration with pinacolborane using [Ru(p-
cymene)Cl2]2 (0.1 mol %). Aromatic aldehydes containing one
or more electron-donating functional groups (entries 2−6, Table
1) or both electron-donating and -withdrawing substituents
(entries 10−11) required 4 to 4.5 h to provide the complete
conversion of aldehydes. Representatively, p-tolyl pinacolboro-
nate ester was isolated (in 98% yield, entry 2) and characterized.
Aromatic aldehydes containing only electron-withdrawing func-
tional groups (entries 7−9) and aliphatic aldehydes underwent
fast hydroboration, and quantitative conversions of aldehydes
(TON > 990) were observed within 3 h at rt. Reactions occur
under neat conditions; solvent is used only for the solid
aldehydes. Progress of the hydroboration reactions was
1
monitored by TLC and H NMR of the reaction mixture,
which confirmed the quantitative conversion of aldehydes.
Hydrolysis of the resulting boronate esters provided the
corresponding alcohols in very high yields (Table 1).
Hydroboration of ketones using complex 1 required heating
the reaction mixture at elevated temperature. When a neat
solution of ketone, pinacolborane, and [Ru(p-cymene)Cl2]2 1
(0.1 mol %) was heated at 60 °C, 60% to >99% conversion of
ketones (TON: 600 to >990) to the corresponding boronate
1
esters was observed by H NMR analyses of the reaction
mixtures. Boronate ester from the reaction of benzophenone and
pinacolborane was isolated in 75% yield (entry 6, Table 2) and
characterized by single-crystal analysis.15 Further hydrolysis of
the boronate esters provides the secondary alcohols in good
yields (Table 2). As observed in the case of aldehydes, both
aliphatic and aryl ketones with different substituents are
tolerated. The efficiency of this catalytic system is remarkable
when compared to the boron-substituted analogue of the Shvo
Initial studies focused on the hydroboration of aldehydes
catalyzed by [Ru(p-cymene)Cl2]2 (1). Upon stirring a neat
solution of benzaldehyde (1 mmol) and pinacolborane (1 mmol,
HBpin = 4,4,5,5-tetramethyl-1,3,2-dioxaborolane) with complex
1 (0.1 mol %) at rt, hydroboration occurs rapidly to provide the
PhCH2OBpin. 1H NMR analysis of the reaction mixture
indicated the quantitative conversion of aldehydes in 4 h
(TON > 990). Upon hydrolysis, benzyl alcohol was obtained in
92% yield after column chromatography (entry 1, Table 1).
Control experiments performed without a catalyst confirmed the
Received: August 14, 2015
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.5b02352
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Organic Letters
Letter
Table 1. Hydroboration of Aldehydes Catalyzed by [Ru(p-
cymene)Cl2]2
Table 2. [Ru(p-cymene)Cl2]2 Catalyzed Hydroboration of
Ketones
a
a
a
Reaction conditions: Ketone (1 mmol), pinacolborane (1 mmol),
and [Ru(p-cymene)Cl2]2 1 (0.1 mol %) are heated together as a neat
b
solution at 60 °C for 15 h. Benzene (1 mL) added as ketone is a
c
1
solid. Conversions of ketones are based on H NMR analysis of the
d
reaction mixture. Isolated yields of 2° alcohols by column
chromatography. n.c.: not calculated.
a
methyl acetate were independently reacted with an equimolar
amount of pinacolborane and 1 (0.1 mol %) in toluene or under
neat conditions at room temperature for 4 h. 1H NMR analyses
of these reaction mixtures indicated the chemoselective hydro-
boration of aldehydes over the other functional groups. The
corresponding alcohols 6−8 were isolated in good yields after
hydrolysis of the boronate esters, and characterization of the
products confirmed further that ketone and ester motifs remain
intact (Scheme 1b).
Reaction conditions: Aldehyde (1 mmol), pinacolborane (1 mmol),
and [Ru(p-cymene)Cl2]2 1 (0.1 mol %) are stirred at room
b
temperature as a neat solution. Benzene (1 mL) added as aldehyde
c
is a solid. Conversions of aldehydes are based on 1H NMR analysis of
d
the reaction mixture. Isolated yields of 1° alcohols by column
chromatography. n.c.: not calculated.
catalyst, which required 70 °C heating for 3 to 4.5 days at 4 mol %
catalyst loading to provide moderate conversions.12
Further, using 1, the challenging chemoselective hydro-
boration of aldehydes over the ketones is explored. Reaction of
equimolar amounts of benzaldehyde, acetophenone, and
pinacolborane were reacted together with 1 (0.1 mol %) under
neat conditions, which resulted in 97% conversion of
1
In situ monitoring of the reaction progress by H NMR
spectroscopy revealed the zero-order kinetics for the hydro-
boration of benzaldehyde (see Figure S1). The hydride region in
the 1H NMR of the reaction mixture displayed a singlet
resonance at δRu−H −10.18 ppm immediately, and the
observation is comparable to that of the hydrosilylation reaction
catalyzed by 1.13 Reaction of [Ru(p-cymene)Cl2]2 1 and
pinacolborane (4 equiv) provided monohydrido bridged
dinuclear ruthenium complex [{(η6-p-cymene)RuCl}2(μ-H-μ-
Cl)] 1b at room temperature (Scheme 2). We previously
prepared and characterized the structure of complex 1b from the
reaction of 1 with triethylsilane, as it was identified as a potential
catalytic intermediate in the hydrosilylation of aldehydes.13
Interestingly, complex 1 reacts with pinacolborane (15 min)
1
benzaldehyde in 4 h. H NMR analysis indicated the presence
of 92% of unreacted acetophenone in the reaction mixture.
Similar chemoselectivity is also observed in competitive catalytic
hydroboration reactions of 1-decanal over the 4-heptanone and
p-nitro benzaldehyde over 1-(4-bromophenyl)propan-2-one
(Scheme 1a). Aldehyde substrates that are embedded with
functional groups such as ketones and esters also exhibited
chemoselective hydroboration. 4-(2-Oxo-2-phenylethoxy)benz-
aldehyde, 2-formylphenyl acetate, and (5-formylfuran-2-yl)-
B
DOI: 10.1021/acs.orglett.5b02352
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 1. Chemoselective Hydroboration of Aldehydes
Catalyzed by [Ru(p-cymene)Cl2]2 1
Scheme 3. Catalytic Hydroboration by an Isolated
Intermediate 1b [{(η6-p-cymene)RuCl}2(μ-H-μ-Cl)]
catalysis,20 hydroboration of benzaldehyde with pinacolborane
was performed using 1 and 2 mol % loadings of 1.21 Similarly,
hydroboration of acetophenone with 1 mol % of 1 was also
carried out and all the reactions were monitored by the 1H NMR,
which indicated that no hydride signal corresponding to 1c
(δRu−H, −13.48 ppm) appears in the reaction mixtures, thus
confirming its noninvolvement in the catalytic hydroboration of
aldehydes and ketones.
On the basis of the above-mentioned observations, we
postulate that under the experimental conditions intermediate
1b reacts with pinacolborane upon splitting into monomeric [(p-
cymene)RuHCl] and [(p-cymene)Ru(Cl)2] complexes22 to
provide Ru(II) intermediate I, which may involve the
intermediacy of Ru(0) species and the B−H activation.23
Reductions of carbonyl functional groups occur by an intra-
molecular 1,3-transfer of a “hydride” ligand to the “carbonyl”
motif to provide II. Further oxidative addition of pinacolborane
to intermediate II results in formation of a Ru(IV) intermediate
III, which reductively eliminates the boronate esters and
generates IV. Coordination of the carbonyl compound to IV
regenerates I to close a catalytic cycle (Scheme 4).
Scheme 4. Plausible Mechanism for the Hydroboration of
Carbonyl Compounds
Scheme 2. Reaction of [Ru(p-cymene)Cl2]2 1 with
Pinacolborane: Preparation of Intermediate 1b
much faster than it reacts with triethylsilane (30 min) to provide
complex 1b quantitatively.16 Complexes 1 and 1b also reacted
further with triethylsilane and provided a mononuclear Ru(IV)
dihydride complex [(η6-p-cymene)Ru(H)2(SiEt3)2] (δRu−H
,
−13.53 ppm).13 Attempts to prepare an analogous pinacolbor-
ane Ru(IV) dihydride complex from the prolonged reaction (12
h) of either complex 1 or 1b with an excess of pinacolborane (4
to 8 equiv) at 50 °C provided a mixture of complexes 1b and 1c
in the ratio 80:20, respectively.17,18 Efforts made to isolate
complex 1c from this reaction mixture proved to be unsuccessful.
Hence, the structure of complex [(η6-p-cymene)Ru-
(H)2(Bpin)2] (δRu−H, −13.48 ppm; δRu−B 34.39 ppm)5 1c is
tentatively assigned based on the analogous silyl ruthenium
dihydride complex [(η6-p-cymene)Ru(H)2(SiEt3)2].13,19
When isolated pure complex 1b (0.1 mol %) was used as a
catalyst in the hydroboration of benzaldehyde with pinacolbor-
ane, quantitative hydroboration was observed in 4 h, confirming
the similar reactivity and efficiency as those of [Ru(p-cymene)-
Cl2]2 1 and thus indicating the potential intermediacy of 1b in
catalysis (Scheme 3). To ascertain any role of complex 1c in
In conclusion, efficient hydroboration of aldehydes and
ketones was achieved using the commercially available and
cheap ruthenium complex [Ru(p-cymene)Cl2]2. At rt, chemo-
selective hydroboration of aldehydes is demonstrated. Mecha-
nistic studies revealed that the reaction of pinacolborane with
[Ru(p-cymene)Cl2]2 1 provides [{(η6-p-cymene)RuCl}2(μ-H-
μ-Cl)] 1b. Perhaps, further oxidative addition of pinacolborane
may generate the catalytically active mononuclear Ru species.
The catalytic cycle consists of 1,3-hydride transfer from the metal
center to the carbonyl group, and reductive elimination of
boronate esters from a Ru(IV) intermediate is postulated.
C
DOI: 10.1021/acs.orglett.5b02352
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
D.-K.; Kim, T.-J.; Jeong, J. H. Polyhedron 2001, 20, 1961−1965.
(e) Bandini, M.; Cozzi, P. G.; de Angelis, M.; Umani-Ronchi, A.
Tetrahedron Lett. 2000, 41, 1601−1605.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.5b02352.
■
S
(10) Chong, C. C.; Kinjo, R. ACS Catal. 2015, 5, 3238−3259.
(11) Gunanathan, C.; Holscher, M.; Pan, F.; Leitner, W. J. Am. Chem.
̈
Soc. 2012, 134, 14349−14352.
Experimental procedures, and spectral and single-crystal
X-ray data for 4f (PDF)
(12) Clark et al. reported the boron-substituted analogue of the Shvo
catalyst for the reductive borylation reactions that required elevated
temperatures, 2 to 4 mol % catalyst, and a prolonged reaction time. See:
Koren-Selfridge, L.; Londino, H. N.; Vellucci, J. K.; Simmons, B. J.;
Casey, C. P.; Clark, T. B. Organometallics 2009, 28, 2085−2090.
(13) Chatterjee, B.; Gunanathan, C. Chem. Commun. 2014, 50, 888−
890.
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: gunanathan@niser.ac.in.
(14) Uncatalyzed hydroboration occurs at CC multiple bonds in the
presence of carbonyl functionalities. (a) Kabalka, G. W.; Yu, S.; Li, N.-S.
Tetrahedron Lett. 1997, 38, 5455−5458.
Author Contributions
†A.K. and B.C. contributed equally to this work.
Notes
(15) See Supporting Information (CCDC 1418431).
(16) The reaction of complex 1 with 0.5 equiv of pinacolborane in
C6D6 was carried out in an NMR tube. Complete formation of complex
1b and ClBpin (observed by 11B NMR, δ = 27.9 ppm) required 5 h at
room temperature.
(17) The attempts made to increase the amount of complex 1c
formations under different conditions failed. In the 1H NMR spectra for
the reaction mixtures, multiple signals appeared in the metal-hydride
region designating the decomposition of intermediate complexes.
(18) The 11B NMR spectrum of this reaction mixture displayed signals
that correspond to HBpin (δ = 28.4 ppm), ClBpin (δ = 27.9 ppm), and a
singlet at δ = 34.39 ppm, which confirmed the presence of Ru-Bpin
species. This boron chemical shift is comparable to that of other Ru-Bpin
complexes reported in the literature; see ref 5.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank SERB New Delhi (SR/S1/OC-16/2012 and SR/S2/
RJN-64/2010) and NISER for financial support. A.K. and B.C.
thank DST and UGC for the fellowships. C.G. is a Ramanujan
Fellow.
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