A highly enantioselective catalyst for the asymmetric Nozaki-Hiyama-Kishi reaction of allylic and vinylic halides

Article abstract of DOI:10.1002/anie.200390265

Catalytic asymmetric addition of vinylic halides and trifiates to aldehydes, with useful levels of stereoinduction, has been achieved for the first time using the salentype ligand (S,S)-5 (see scheme; PMB=para-methoxybenzyl), which contains the novel endo

Full text of DOI:10.1002/anie.200390265

Communications
1
. cat. CrCl2 / cat. CrL*
OH
R2
Mn, Me3SiCl
1
2
R CHO
+
R X
R1
2
. Hydrolysis
1
2
3
H
N
H
N
RR
tBu
OH HO
tBu
tBu
(R,R)-4
tBu
Highly Enantioselective Catalysts
S
S
N
N
A Highly Enantioselective Catalyst for the
Asymmetric Nozaki–Hiyama–Kishi Reaction of
Allylic and Vinylic Halides**
tBu
OH
HO
tBu
tBu
(S,S)-5
tBu
Albrecht Berkessel,* Dirk Menche, Christoph A. Sklorz,
Michael Schröder, and Ian Paterson
Scheme 1. Ligands for the catalytic asymmetric Nozaki–Hiyama–Kishi
reaction; diaminocyclohexane-derived salen 4 and the novel ligand 5,
based on endo,endo-2,5-diaminonorbornane (DIANANE).
Dedicated to Professor Emanuel Vogel
on the occasion of his 75th birthday
enantioselective version of this reaction.[2–5] Nevertheless,
only one such example appears to have been reported,
namely by the research group of Umani-Ronchi, which uses
the salen ligand 4, derived from trans-1,2-diaminocyclohex-
The nucleophilic addition of organochromium reagents to
aldehydes (Scheme 1) is a versatile carbon–carbon bond-
forming reaction that is compatible with a wide range of
functionality in both components.[1] Alarge number of
applications, particularly in the synthesis of structurally
diverse natural products, have resulted. The organochromium
reagents are easily prepared in situ by the oxidative addition
of chromium(ii) species to allyl, propargyl, aryl, and vinyl
[
5]
ane (Scheme 1). Whereas the enantioselectivities observed
for allyl chorides were high (for example, up to 84% ee in the
addition to benzaldehyde), the use of the ligand 4 does not yet
provide a broadly applicable synthetic method. In particular,
the substrate spectrum is still fairly narrow; other halides such
as allyl bromide and iodide were found to add with only
moderate (52% ee) or no selectivity to benzaldehyde. As an
asymmetric NHK process for generating enantiomerically
enriched allylic alcohols would be extremely valuable, the
omission of vinyl halides as substrates for this reaction is
II
halides or triflates 2 (requiring catalytic amounts of a Ni salt
2
for sp carbon centers), and efficiently add to aldehydes 1 to
[
1]
give the corresponding alcohols 3 in good yields (Scheme 1).
While the original procedure for the Nozaki–Hiyama–Kishi
NHK) reaction relies on the use of stoichiometric quantities
[
5a–e]
(
significant.
We now report our preliminary results using
of chromium(ii) chloride, Fürstner et al. have developed a
the novel salen ligand (S,S)-5 in NHK reactions, which
surpasses the current limitations of 4 by promoting the
catalytic addition of allylic and vinylic halides (and triflates)
to aromatic and aliphatic aldehydes with synthetically useful
levels of asymmetric induction.
method requiring only catalytic amounts of the active
II
Cr species; cheap and toxicologically benign manganese is
used as the reducing agent, and a trialkylchlorosilane effects
[
2]
the perpetuation of the catalytic cycle. This important
finding triggered numerous efforts to develop a catalytic and
Salen ligands used in asymmetric catalysis are mainly
based on commercially available chiral 1,2-diamines and
various salicylic aldehyde components. Comparatively little
attention has been paid to significantly modifying the diamine
backbone, for example, by attenuating the separation of the
nitrogen atoms. We imagined that this parameter might play a
particularly important role in further improving the catalytic
properties and, thus, we devised a novel chiral diamine that
[*] Prof. Dr. A. Berkessel, Dr. D. Menche, Dr. C. A. Sklorz,
Dipl.-Chem. M. Schröder
Institut für Organische Chemie
Universität zu Köln
Greinstrasse 4, 50939 Köln (Germany)
Fax: (+49)221-470-5102
E-mail: berkessel@uni-koeln.de
[
6,7]
exhibits a larger nitrogen-atom separation.
endo,endo-2,5-diamino-norbornane (9,
We envisaged
DIANANE,
Prof. Dr. I. Paterson
University Chemical Laboratory
Lensfield Road, Cambridge CB2 1EW (United Kingdom)
Scheme 2) to be a promising candidate. This novel building
block has the advantages of possessing C symmetry and
having a rigid hydrocarbon backbone. In our synthesis of 9,
the diketone 6 is converted to a bis(endo diamine) by
[
**] This work was supported by the European Community (Research
Training Network “Combinatorial Catalysis”) and by the Fonds der
Chemischen Industrie. We thank Dr. Ira Fiolia for technical support.
2
1
032
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However, instead of relying on the known enantioselective,
but multistep approach to 6/ent-6 from norbornadiene (7),
b
[8]
O
O
H
a
O
H
O
O
we employed the readily available racemic form of the
rac-6
[9]
O
diketone (rac-6), and resolved the racemic mixture of
7
DIANANE at a later stage. As summarized in Scheme 2, the
N,N’-bistosylates of DIANANE (8 and ent-8) were efficiently
separated by preparative HPLC on a chiral stationary phase.
Absolute configurations of the crystalline sulfonamides 8 and
c-f
S
S
i
i
(
S,S)-5
NH2
NH2
(
S,S)-9
g, h
[10]
ent-8 were determined by X-ray crystallography. Reductive
NHTs
NHTs
N-detosylation followed by condensation with 3,5-di-tert-
butyl salicylic aldehyde afforded the desired salen ligands
(S,S)-5 and (R,R)-5, respectively.
R
R
rac-8
(R,R)-5
NH2
R,R)-9
Scheme 2. Enantiodivergent synthesis of (S,S)-5 and (R,R)-5.
NH2
An evaluation of the catalytic performance of the (S,S)-5
and (R,R)-5 ligands was performed. Typical reaction condi-
(
[
2,5]
tions
comprised 10 mol% of CrCl , an excess of Mn and
3
[
9]
[9]
a) HCO H, reflux, 84%; b) Jones reagent, 44%; c) NH OH·HCl,
II
2
2
Me SiCl, and in situ preparation of the Cr complex, in the
3
EtOH, reflux, 1 h; d) NiCl , NaBH , MeOH, ꢀ358C to ꢀ208C, 1 h, 70–
2
4
presence of NEt3 and MeCN as solvent (Table 1). The
addition of allyl bromide to benzaldehyde proceeded asym-
metrically (46% ee, room temperature). After optimization
of the reaction parameters (solvent, concentration, and
temperature), the corresponding homoallylic alcohol was
obtained with high enantioselelectivity (90% ee) and good
yield (72%; Table 1, entry 1). THF proved to be the best
7
5% (over two steps); e) TsCl, NEt , CH Cl , ꢀ788C to RT; f) crystalli-
3
2
2
zation from MeOH, 35% (over two steps); g) preparative HPLC, Chir-
ꢀ1
alpak AD, 50 cm, 5 cm diameter, flow: 80 mLmin , eluent: hexane/iso-
propanol 60:40, retention times: 24–33 min for (R,R)-8 and 46.5–
6
2.5 min for (S,S)-8; h) Li, NH , ꢀ338C, 80 min, 85%; i) 3,5-di-tert-
3
butyl salicylic aldehyde, MeOH, RT, 30 min, 76–81%.
solvent among those tested (DMF, DME, CH CN), while a
3
treatment of the corresponding dioxime with NaBH /NiCl2
catalyst concentration of 0.025m gave the best results.
Optimal enantioselectivity was observed for the allyl bro-
mide/benzaldehyde system at 58C (90% ee). Avariety of
different substrates was screened under these conditions. In
4
(
Scheme 2). Consequently, the pure enantiomers of DIA-
NANE 9 (that is, (S,S)-9 and (R,R)-9) can be prepared from
the enantiomerically pure diketone 6 and ent-6, respectively.
Table 1: Catalytic, enantioselective Nozaki–Hiyama–Kishi-type additions in the presence of ligand (S,S)-5.
Entry
Aldehyde
Halide
Product
ee [%]
90[d,e]
31[d,f]
79[d,e]
54[e,h]
64[f,h]
92[e,h]
75[h,j]
Yield [%][b]
Reaction temperature[c]
1
2
3
4
5
6
7
72
58C
RT
[g]
76
RT
78
RT
[g]
RT
69[i]
59[i]
108C
158C
8
61[h,k,l]
54[i]
208C
[
a] For entries 7 and 8, the reaction was run in the presence of 0.02 equiv of NiCl . [b] Yield after flash chromatography. [c] Reaction temperature was
2
optimized for entries 1, 2, 5, 6, 7, and 8. [d] Enantiomeric excess was determined by gas chromatography (GC) of the corresponding TMS ethers on a
chiral stationary phase (Macherey–Nagel: Lipodex A, 958C). [e] Absolute configurations were assigned by comparison of optical rotations with
literature data.[
5d,11,12]
[f] Absolute configuration based on GC/HPLC data (that is, comparison of the products of entries 2 and 1 and of the products of
entries 3 and 5 on an analytical scale). [g] Not determined. [h] Enantiomeric excess determined by HPLC on a chiral phase (Daicel: Chiralcel OD-H).
i] Some debenzylation occured as a side reaction. [j] Absolute configuration determined by 1) oxidative cleavage (ozonolysis), 2) reduction to 1,2,4-
[
[
13]
butanetriol, 3) GC co-injection with a sample of known absolute configuration. [k] Reaction was performed with (R,R)-5. [l] Assignment of absolute
configuration in analogy to entry 7.
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Communications
contrast to the salen ligand 4, ligand 5 was also able to effect,
for the first time, an enantioselective addition of allyl iodide
stirred at that temperature. When the aldehyde was completely
consumed (as confirmed by thin-layer chromatography (TLC)),
saturated aqueous NaHCO was added. After filtration and evapo-
3
(
(
Table 1, entry 2). Allyl chloride added with similar selectivity
84% ee using 4, versus 79% ee using DIANANE-based 5;
ration, the aqueous phase was extracted with Et O. After evaporation
[
5]
2
of the combined organic phases, the residue was dissolved in THF
Table 1, entry 3). Of the three allyl halides tested, the bromide
thus afforded the best enantioselectivity. The related b-
methylallyl halides (Table 1, entries 4 and 5) reacted just as
smoothly as the allyl halides. However, the observed enan-
tioselectivities for these compounds (54% and 64% ee for the
chloride and bromide, respectively) were not as high as for
allyl bromide (90% ee). As a model for projected applications
in polyketide natural-product synthesis, we tested PMB-
(
1 mL). Aqueous 1m HCl (0.5 mL) was added and the mixture was
stirred until desilylation was complete (confirmed by TLC). The
solvent was removed, the residue extracted with Et O, and the
combined organic phases were dried over MgSO . Evaporation of the
solvent and flash chromatography (hexane/Et O 4:1) gave (R)-1-
phenyl-3-buten-1-ol as a pale-yellow oil (26.7 mg, 180 mmol, 72%
yield, 90% ee).
2
4
2
Received: October 21, 2002 [Z50397]
protected 3-hydroxypropanal (PMB = para-methoxybenzyl),
shown in entry 6 of Table 1.[
12,14,15]
Again, after optimizing the
reaction temperature, coupling with allyl bromide occurred
with high enantioselectivity (92% ee).[
16]
[
1] For reviews, see: a) A. S. K. Hashmi, J. Prakt. Chem. 1996, 338,
91 – 495; b) L. A. Wessjohann, G. Scheid, Synthesis 1999, 1—36;
The encouraging results achieved with allylic halides
prompted us to examine the use of our catalytic NHK process
with vinyl iodides and triflates for the enantioselective
4
c) A. Fürstner, Chem. Rev. 1999, 99, 991 – 1045; d) A. Fürstner,
Chem. Eur. J. 1998, 4, 567 – 570.
II
synthesis of allylic alcohols. As expected, 2 mol% of Ni (in
[2] A. Fürstner, N. Shi, J. Am. Chem. Soc. 1996, 118, 12349 – 12357.
[
3] a) C. Chen, K. Tagami, Y. Kishi, J. Org. Chem. 1995, 60, 5386 –
5387; b) Y. Kishi, Tetrahedron 2002, 58, 6239 – 6258; c) H. S.
Schrekker, M. W. G. de Bolster, R. V. A. Orru, L. A. Wessjo-
hann, J. Org. Chem. 2002, 67, 1975 – 1981.
the form of NiCl ) was required for the coupling reaction to
2
[
2]
occur efficiently. Under these reaction conditions, the
addition of E-1-iodohex-1-ene[ to the PMB-protected 3-
hydroxypropanal test system afforded the corresponding E-
allylic alcohol adduct in an unoptimized 59% yield with
17]
[
4] For asymmetric versions of the NHK reaction using stoichio-
metric amounts of chiral organochromium agents, see: a) B.
Cazes, C. Verniere, J. GorØ, Synth. Commun. 1983, 13, 73 – 79;
b) K. Sugimoto, S. Aoyagi, C. Kibayashi, J. Org. Chem. 1997, 62,
[
18]
7
5% ee (Table 1, entry 7). Likewise, the vinyl triflate
(
entry 8, Table 1) added to this same aldehyde to produce
2322 – 2323; and ref. [3a].
the isomeric allylic alcohol with 61% ee. Notably, these last
two addition reactions represent the first examples of
synthetically useful levels of asymmetric induction being
realized for catalytic, enantioselective NHK reactions of
vinylic halide and triflate substrates.
[
5] a) M. Bandini, P. G. Cozzi, P. Melchiorre, A. Umani-Ronchi,
Angew. Chem. 1999, 111, 3558 – 3561; Angew. Chem. Int. Ed.
1999, 38, 3357 – 3359; b) M. Bandini, P. G. Cozzi, A. Umani-
Ronchi, Polyhedron 2000, 19, 537 – 539; c) M. Bandini, P. G.
Cozzi, A. Umani-Ronchi, Angew. Chem. 2000, 112, 2417 – 2420;
Angew. Chem. Int. Ed. 2000, 39, 2327 – 2330; d) M. Bandini, P. G.
Cozzi, A. Umani-Ronchi, Tetrahedron 2001, 57, 835 – 843; e) M.
Bandini, P. G. Cozzi, P. Melchiorre, S. Morganti, A. Umani-
Ronchi, Org. Lett. 2001, 3, 1153 – 1155; f) After submission of
this manuscript, a report by Kishi et al. on a catalytic enantio-
selective process using an oxazoline sulfonamide ligand
appeared: H.-W. Choi, K. Nakajima, D. Demeke, F.-A. Kang,
H.-S. Jun, Z.-K. Wan, Y. Kishi, Org. Lett. 2002, 4, 4435 – 4438.
However, the enantioselectivities reported are not as high as our
best examples.
In summary, we have demonstrated that our DIANANE-
based salen ligands, (S,S)-5 and (R,R)-5, promote efficient
and highly enantioselective catalytic Nozaki–Hiyama–Kishi
reactions. With this novel ligand modification, the addition of
various organochromium intermediates to aromatic and
aliphatic aldehydes proceeded under catalytic conditions
with good levels of stereoinduction (up to 92% ee). Notably,
the asymmetric additions of allyl iodide and, in particular,
vinyl halides and triflates to aldehydes were achieved with
useful levels of enantioselectivity. We are currently exploring
the generality and functional-group compatibility of this
catalytic carbon–carbon bond-forming process, together with
examining its utility with chiral substrates, in the context of
projected applications to the stereocontrolled synthesis of
more complex structures, such as those that occur in polyke-
tide natural products.
[
[
6] For a review of applications of Cr–salen complexes in asym-
metric catalysis, see: M. Bandini, P. G. Cozzi, A. Umani-Ronchi,
Chem. Commun. 2002, 919 – 927.
7] For two examples, see: a) X.-G. Zhou, J.-S. Huang, X.-Q. Yu, Z.-
Y. Zhou, C.-M. Che, J. Chem. Soc. Dalton Trans. 2000, 1075 –
1080; b) D. Seebach, A. K. Beck, A. Heckel, Angew. Chem.
2001, 113, 96 – 142; Angew. Chem. Int. Ed. 2001, 40, 92 – 138.
[
[
8] a) T. Hayashi, Acta Chem. Scand. 1996, 50, 259 – 266; b) A.
Weissfloch, R. Azerad, Bioorg. Med. Chem. 1994, 2, 493 – 500.
9] R. T. Hawkins, R. S. Hsu, S. G. Wood, J. Org. Chem. 1978, 43,
4648 – 4650.
Experimental Section
[10] Afull account of the synthesis and configurational assignment of
(þ)- and (ꢀ)-DIANANE (9) will be published elsewhere.
[11] K. Ishihara, M. Mouri, Q. Gao, T. Maruyama, K. Furuta, H.
Yamamoto, J. Am. Chem. Soc. 1993, 115, 11490 – 11495.
[12] A. B. Smith III, K. P. Minibiole, P. R. Verhoest, M. Schelhaas, J.
Am. Chem. Soc. 2001, 123, 10942 – 10953.
Typical Procedure: Anhydrous THF (1 mL) was added to CrCl
3
(4.0 mg, 25.0 mmol) and Mn (42 mg, 750 mmol) in a dried Schlenk
tube under argon, and the mixture was stirred for 1 h at room
temperature. After addition of the ligand (S,S)-5 (14.0 mg, 25.0 mmol)
and anhydrous NEt3 (7 mL, 5.0 mg, 50 mmol), the suspension was
stirred for another hour at room temperature.[ Finally, allyl bromide
was added (32 mL, 45.4 mg, 375 mmol). After 1 h, the mixture was
19]
[13] V. K. Tandon, A. M. van Leusen, H. Wynberg, J. Org. Chem.
1983, 48, 2767 – 2769.
cooled to 58C, PhCHO (25 mL, 26.2 mg, 250 mmol) and Me SiCl
[14] Y. Wu, L. Esser, J. K. De Brabander, Angew. Chem. 2000, 112,
4478 – 4480; Angew. Chem. Int. Ed. 2000, 39, 4308 – 4310.
3
(48 mL, 41.2 mg, 380 mmol) were added, and the suspension was
1
034
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Angewandte
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[
[
15] The synthesis of the aldehyde was performed according to:
a) M. J. Martinelli, J. Org. Chem. 1990, 55, 5065 – 5073; b) T.
Oka, A. Murai, Tetrahedron 1998, 54, 1 – 20.
16] The possibility to recover the valuable ligand by column
chromatography after aqueous work-up further adds to the
efficiency of our process. Usually, at least 80% of ligand could be
recovered in pure form.
[
[
[
17] J. K. Stille, J. H. Simpson, J. Am. Chem. Soc. 1987, 109, 2138 –
2152.
18] K. Takai, K. Sakogawa, Y. Kataoka, K. Oshima, K. Utimoto,
Org. Synth. 1995, 72, 180 – 188.
19] For entries 7 and 8, 0.02 equiv of NiCl were added prior to the
2
halide.
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1035