Design of boron bis-oxazolinate (B-BOXate) complexes: A new class of stable organometallic catalysts

Article abstract of DOI:10.1039/b103571c

A new class of remarkably stable B-BOXate complexes has been synthesised, isolated and employed as chiral catalysts for asymmetric reduction of variously substituted prochiral ketones.

Full text of DOI:10.1039/b103571c

Design of boron bis-oxazolinate (B-BOXate) complexes: a new class of
stable organometallic catalysts
Marco Bandini, Pier Giorgio Cozzi,* Magda Monari, Rossana Perciaccante, Simona Selva and
Achille Umani-Ronchi*
Dipartimento Chimico ‘G. Ciamician’, Università di Bologna, Via Selmi 2, 40126 Bologna, Italy.
E-mail: pgcozzi@ciam.unibo.it; umani@ciam.unibo.it; Fax: +39-51-2099515; Tel: +39-51-2099509
Received (in Cambridge, UK) 20th April 2001, Accepted 4th June 2001
First published as an Advance Article on the web 27th June 2001
A new class of remarkably stable B-BOXate complexes has
been synthesised, isolated and employed as chiral catalysts
for asymmetric reduction of variously substituted prochiral
ketones.
Enantioselective catalytic processes have emerged as among the
most powerful of methodologies for the preparation of enantio-
1
merically enriched compounds. Of all the catalytic asymmetric
procedures, the use of metal complexes bearing chiral ligands is
receiving a great deal of attention from the chemical commu-
nity.2 In the class of the ‘privileged ligands’ reported in
literature, chiral bis-oxazoline (BOX) ligations have been
demonstrated to be effective motifs in many stereocontrolled
3
reactions. Normally, bis-oxazoline metal complexes are de-
signed to behave as chiral Lewis acids, and free coordination
sites are available for the incoming electrophile. Our attention
was addressed towards the design of stable and coordinatively
saturated BOX complexes where simultaneous binding of
Fig. 1 An ORTEP plot of the molecular structure of 3. Thermal ellipsoids
are drawn at the 30% probability level. Selected bond lengths (Å) and angles
°): B–N(1) 1.541(2), B–N(2) 1.548(2), B–O(3) 1.479(2), B–O(4) 1.481(2),
N(1)–C(1) 1.494(2), N(1)–C(3) 1.316(2), N(2)–C(5) 1.319(2), N(2)–C(7)
.493(2), C(3)–C(4) 1.375(2), C(4)–C(5) 1.370(2); O(3)–B–O(4) 104.5(1),
N(1)–B–N(2) 105.8(1), O(3)–B–N(1) 111.8(1), O(4)–B–N(1) 111.3(1),
O(3)–B–N(2) 111.6(1), O(4)–B-N(2) 111.9(1). Dihedral angle between
plane N(1)–B–N(2) and O(3)–B–O(4) is 89.69(8).
4
electrophiles and nucleophiles is possible. With this in mind
our interest was drawn to the preparation of coordinatively
saturated boron bis-oxazolinate complexes. We discovered that
the achiral BOX5 1 reacted smoothly with catecholborane
(
1
(CATBH) in CH
2
Cl
2
affording, after removal of the solvent, the
boron bis-oxazolinate adduct 3 (B-BOXate) as a white solid
1
13
stable to moisture in 85% yield.† The H NMR, C NMR and
11
B NMR spectroscopy investigations supported the formation
of a single symmetric complex derived from the reaction
between the CATBH and the BOX 1 (Scheme 1). To the best of
our knowledge, B-BOXate complexes have not been reported
until now. As a matter of fact, although the BOX ligands are
easily deprotonated, only a few cases of BOXate–metal
C(2) and C(6) atoms lie out the plane of their oxazoline rings
[±0.223(5) Å] therefore the actual idealised symmetry is only
C .
2
Employing chiral BOX ligands, the corresponding B-
BOXate complexes can be isolated as stable solids. For
instance, starting from the 2,2A-methylenebis[(4R,5S)-4,5-di-
phenyl-2-oxazoline] 2 and CATBH following the synthetic
protocol employed for 3 the chiral B-BOXate 4 is isolated
6
complexes have been described. Diagnostic signals for 3 are
13
the singlet for the proton bridge at d = 4.45 ppm, the C signal
at d = 57.8 ppm for the methine carbon of the ligand and the 11
B
signal at d = 8.87 ppm typical for a tetrahedral coordination of
(diagnostic signals for 4 are as follows: H NMR d = 5.03 ppm
1
7
13
the boron atom. These findings were also confirmed by an X-
and C NMR d = 57.8 ppm). In the course of our studies on the
ray crystallographic analysis of 3.‡ The structure reported in
Fig. 1 shows that the BOX and the catechol motifs lie in two
perpendicular planes, whereas the boron atom adopts a
tetrahedral coordination slightly deviating from the idealised
geometry as a consequence of the ring constraints. The
molecule would conform to an idealised C2v symmetry, but
enantioselective reduction of prochiral ketones in the presence
of M-BOX complexes,6a,8 we found that the complex 3 was able
to catalyse effectively the reduction of acetophenone with
CATBH yielding the corresponding 1-phenylethanol in 86%
yield after 18 h (Scheme 2). The use of 4 in catalytic amount (8
mol%) gave the desired (R)-1-phenylethanol (6a) in 80% yield
and 44% enantiomeric excess. With the aim of searching for the
optimal reaction protocol we screened, in the asymmetric
Scheme 1 Reagents and conditions: (i) BOX (1 eq.), CATBH (1.5 eq.),
Scheme 2 Reagents and conditions: (i) 5 (1 eq.), B-BOX (8 mol%), CATBH
2
CH Cl
2
, rt, 4 h.
2 2
(2 eq.), CH Cl , 0 °C. (ii) NaOH (2 M).
1318
Chem. Commun., 2001, 1318–1319
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b103571c

Notes and references
†
Synthesis of the B-BOXate 3: A 25 mL round-bottom flask containing a
stirring bar was charged with dry CH Cl (4 mL), BOX 1 (105 mg, 0.5
2
2
mmol) and CATBH (80 mL, 0.75 mmol) at 0 °C. The resulting solution was
stirred 4 h, then the solvent was evaporated under reduced pressure. The
crude white product obtained was washed with dry Et
2
O (5 mL), collected
(CDCl , 300 MHz)
(CDCl , 50 MHz)
(Ref. BF ·OEt ): 8.87;
(1) 3.95 (s, 4H), 3.29 (s,
(3) 160.2, 79.5, 67.3, 28.6, 28.2; d (CATBH) 29.92
by filtration and dried under vacuum. Yield = 85%. d
H
3
6
1
.71 (m, 4H), 4.46 (s, 1H), 4.10 (s, 4H), 1.30 (s, 12H); d
50.7, 119.1, 109.3, 109.0, 81.7, 62.8, 57.8, 26.3; d
C
3
B
3
2
diagnostic chemical shifts for 1 and CATBH: d
H), 1.26 (s, 12H); d
d, JB-H = 554.1 Hz).
Crystal data for 3: C17
b = 9.4340(4), c = 11.1411(4) Å, a = 67.378(2), b = 75.067(2), g =
H
2
C
B
(
‡
21 4 2
H O BN , M = 328.17, triclinic, a = 8.9871(3),
Fig. 2 BOX ligands.
3
¯
7
7.487(2)°, U = 835.12(5) Å , T = 293 K, space group P1 (No. 2), Z = 2,
21
m(Mo-Ka) = 0.092 mm , 11678 reflections measured by Bruker AXS
SMART 2000 diffractometer with a CCD detector, 4866 unique (Rint
.0293) which were used in all calculations. Final R1(F) = 0.0455 [I >
reduction, other chiral C
2
bis-oxazoline ligands (BOX 7–9, Fig.
=
2
) preparing the catalytic precursors in situ, in order to simplify
0
9
2
the procedure.
2s(I)] and wR2(F ) = 0.1260 (all data). Software contained in the
The best result was obtained using 8 mol% of the BOX 9 that
furnished the enantioenriched alcohol in 76% ee (Table 1, entry
),§ while the use of non-enolizable BOXs such as the PyBOX
, significantly decreased the enantioselectivity (ee = 18%,
SHELXTL (5.1) library (G. M. Sheldrick, Bruker AXS, Madison, WI).
CCDC 163357. See http://www.rsc.org/suppdata/cc/b1/b103571c/ for crys-
tallographic files in .cif format.
4
8
§
Catalytic reduction reaction: To a stirring solution of 9 (13.2 mg, 0.04
mmol) in dry CH Cl (2 mL) at 0 °C was added CATBH (100 mL, 1 mmol).
2
2
entry 3). Moreover, the catalytic protocol can be successfully
applied in the reduction of branched aromatic ketones and a-
halo ketones10 (Table 1, entries 5–8). Although the mechanism
of the present reduction is still unclear, a cooperative action in
which ketones and CATBH simultaneously bind to the chiral
catalyst (chemzyme) could be invoked. In summary, the design
of a new class of B-BOXate complexes and their use in the
catalytic asymmetric reduction of ketones is presented. The
fine-tuning of the stereo-electronical features (both the bis-
oxazoline and the catechol motifs can be opportunely matched),
makes these systems promising catalysts for a variety of
stereocontrolled organic transformations.
The clear mixture was stirred for 2–3 h at the same temperature then
acetophenone (58 mL, 0.5 mmol) was added by syringe. The reaction was
kept without stirring for 48–72 h at 0 °C, quenched with NaOH (2 mL, 2 M)
2 2 4
and then stirred for 10 min. After the usual workup (Et O, Na SO ) the
crude product was purified by flash chromatography (cyclohexane–Et O
2
85+15) to afford the (R)-(+)-phenylethanol as a pale yellow oil in 78% yield
and 76% ee (Chiral GC analysis, Megadex-5 column).
1
2
B. M. Trost, Angew. Chem., Int. Ed. Engl., 1995, 34, 259.
(a) A. Pfaltz, E. N. Jacobsen, H. Yamamoto, ed., in Comprehensive
Asymmetric Catalysis, Springer, Berlin, 1999; (b) I. Ojima, ed., in
Catalytic Asymmetric Synthesis, Wiley, VCH, New York, 2nd edn.,
2
000.
Table 1 Enantioselective reduction of ketones in the presence of boron
BOX complexes as catalysts
3
4
For a recent and comprehensive review see: A. K. Ghosh, P. Mathivanan
and J. Cappiello, Tetrahedron: Asymmetry, 1998, 9, 1.
Chiral oxazaborolidines are known to act as chemzyme systems in
which nucleophile and electrophile are bound in proximity affording a
synergic catalytic action see: E. J. Corey and C. J. Helal, Angew. Chem.,
Int. Ed., 1998, 37, 1986.
Entrya
BOX
Ketone
Yield (%)b Ee (%)c
Config.d
1
2
3
4
5
6
7
8
a
2
7
8
9
9
9
9
9
5a
5a
5a
5a
5b
5c
5d
5e
80
40
52
78
65
85
56
78
67
30
18
76
76
84
86
72
S
S
S
R
R
S
S
R
5
6
For the synthesis of 1 see ref. 2.
(a) Ti-BOXate: M. Bandini, P. G. Cozzi, L. Negro and A. Umani-
Ronchi, Chem. Commun., 1999, 39; (b) Zn-BOXate: M. Nakamura, A.
Hirai and M. Sogi, J. Am. Chem. Soc., 1998, 120, 546; R. P. Singh, Bull.
Soc. Chim. Fr., 1997, 134, 765; (c) Mg-BOXate: V. Schulze and R. W.
Hoffmann, Chem. Eur. J., 1999, 5, 337; (d) Yb/Ln-BOXate: H. W.
Görlitzer, M. Spiegler and R. Anwander, J. Chem. Soc., Dalton Trans.,
e
The reactions were carried out as described in the note §. b Isolated yields
1
999, 4287; (e) Cu-BOXate: D. Müller, G. Umbricht, B. Weber and A.
after flash chromatography. c Evaluated by chiral GC analysis with a chiral
cyclodextrin Megadex-5 column. The absolute configuration was assigned
Pfaltz, Helv. Chim. Acta, 1991, 74, 1; R. Schumacher, F. Dammast and
H. U. Reißig, Chem. Eur. J., 1997, 3, 614; (f) Rh-BOXate: J. M. Brown,
P. J. Guiry, D. W. Price, M. B. Hursthouse and K. Karalulov,
Tetrahedron: Asymmetry, 1994, 5, 561.
For a recent elegant study concerning trigonal and tetrahedral structure
of chiral boron complexes see: K. Ishihara, H. Kurihara, M. Matsumoto
and H. Yamamoto, J. Am. Chem. Soc., 1998, 120, 6920.
M. Bandini, P. G. Cozzi, M. de Angelis and A. Umani-Ronchi,
Tetrahedron Lett., 2000, 41, 1601.
Other boron reducing agents were tested in the asymmetric reduction
d
D
by comparison of the [a] value reported in the literature (see: ref. 6a, 8).
e
The corresponding epoxide was isolated in 24% yield (ee = 86% ) as a by-
product of the reaction.
7
Acknowledgements are made to C.N.R. and M.U.R.S.T.
Progetto Nazionale ‘Stereoselezione in Sintesi Organica:
8
9
(
Metodologie ed Applicazioni’) and Bologna University (funds
for selected research topics) for the financial support of these
researches. Dr Rossana Perciaccante thanks C.I.N.M.P.I.S. for a
research grant. Dr Chris Senanayake (Sepracor INC.) is
acknowledged for the generous gift of chiral (1R,2S)-cis-
(i.e. BH
3 2 3 3
·S(Me) , BH ·2,6-lutidine and BH ·4-phenylmorpholine).
However the enantiomeric excesses were significantly lower.
1
0 Aliphatic carbonyl substrates afforded the secondary alcohol in low
chemical and optical yields (2-methylheptan-3-one: yield = 31%, ee =
26%).
1-amino-2-indanol.
Chem. Commun., 2001, 1318–1319
1319
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