Chemoenzymatic Dynamic Kinetic Asymmetric Transformations of β-Hydroxyketones

Article abstract of DOI:10.1002/chem.202102683

Herein we report on the development and application of chemoenzymatic Dynamic Kinetic Asymmetric Transformation (DYKAT) of α-substituted β-hydroxyketones (β-HKs), using Candida antartica lipase B (CALB) as transesterification catalyst and a ruthenium complex as epimerization catalyst. An operationally simple protocol allows for an efficient preparation of highly enantiomerically enriched α-substituted β-oxoacetates. The products were obtained in yields up to 95 % with good diastereomeric ratios.

Full text of DOI:10.1002/chem.202102683

Accepted Article
Accepted Article
Title: Chemoenzymatic Dynamic Kinetic Asymmetric Transformations
of β-Hydroxyketones
Authors: Jan-E. Bäckvall, Simon Hilker, Daniels Posevins, and C.
Rikard Unelius
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of the final Version of Record (VoR). This work is currently citable by
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To be cited as: Chem. Eur. J. 10.1002/chem.202102683
Link to VoR: https://doi.org/10.1002/chem.202102683
01/2020

10.1002/chem.202102683
Chemistry - A European Journal
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Chemoenzymatic Dynamic Kinetic Asymmetric Transformations
of β-Hydroxyketones
Simon Hilker,[a] Daniels Posevins,* [a] C. Rikard Unelius,[b] and Jan-E. Bäckvall*[a]
Dedication ((optional))
[a]
[b]
S. Hilker, Dr. D. Posevins, Prof. Dr. J.-E. Bäckvall
Department of Organic Chemistry, Arrhenius Laboratory
Stockholm University, 10691 Stockholm (Sweden)
jeb@organ.su.se
daniels.posevins@gmail.com
Prof. Dr. C. R. Unelius
Department of Chemistry and Biomedical Science
Linnaeus University, 39231 Kalmar (Sweden)
Supporting information for this article is given via a link at the end of the document.
Abstract: Herein we report on the development and application of
chemoenzymatic Dynamic Kinetic Asymmetric Transformation
(DYKAT) of α-substituted β-hydroxyketones (β-HKs), using Candida
antartica lipase B (CALB) as transesterification catalyst and a
ruthenium complex as epimerization catalyst. An operationally simple
protocol allows for an efficient preparation of highly enantiomerically
enriched α-substituted β-oxoacetates. The products were obtained in
yields up to 95% with good diastereomeric ratios.
takes advantage of a facile dehydrogenation step when
employing Ru-complex Ia together with an acyl donor affording γ-
oxoacetates as products (Scheme 1b).[11b]
To date various metal-based racemization catalysts have
been reported to be compatible with enzyme catalysis, including
ruthenium-based complexes. Early DKR systems employed a
combination of lipase CALB and Shvo’s catalyst (Ia).[12] Park and
co-workers later introduced a new type of RuCl-complexes with
superior racemization properties.[13] The Bäckvall group
developed a highly potent RuCl-complex (II), which has since then
found application in various DKR and DYKAT systems.[6b-d,14] With
the latter catalyst racemization of 1-phenylethanol takes place at
room temperature in minutes.[14a,b] Further, this catalyst system
suppresses the commonly occurring side reaction of substrate
oxidation, which is a common problem with the early DKR
systems employing catalyst Ia.[6a]
Asymmetric synthesis remains an important part of organic
chemistry, strongly impacting other scientific areas.[1] Various
areas of chemical industry have a stable growing demand of
optically pure compounds,[2] with the resolution of racemic
mixtures still being the preferred method industrially.[3] Ever since
the possibility to combine enzymes and transition metals in one-
pot procedures was reported,[4] considerable efforts into com-
bining enzymes and transition metals in catalytic systems have
been undertaken.[5] Development of systems combining in-situ
transition metal-catalyzed racemization with enzymatic kinetic re-
solution (KR) has resulted in so-called dynamic kinetic resolution
(DKR), efficiently resolving racemic mixtures of e. g. sec-alcohols
in theoretically quantitative yields,[6] providing convenient access
to valuable functionalized alcohols.[7] Further, chemoenzymatic
DKR procedures have been successfully applied in the resolution
of α-hydroxyketones or the asymmetric syntheses of diaryl diols.[8]
Recently, also systems using organocatalysis or photocatalysis
cooperatively with enzyme catalysis or bi-enzymatical DKR
systems have been developed and applied.[9] Chemoenzymatic
DYKAT[10] protocols have been developed for the diastereo- and
enantioselective transformations of diastereomeric mixtures of
diols[11] and found application in the synthesis of enantiomerically
pure (+)-solenopsin A.[11c] We have previously developed a
DYKAT of 1,3-diols to access enantiomerically pure syn-1,3-
diacetates combining enzymatic resolution and Ru-catalyzed
epimerization additionally including intramolecular acyl migration
in 1,3-syn-diol monoacetates (Scheme 1a).[11a] Another example
includes preparation of γ-hydroxyketones from 1,4-diols that
Scheme 1. Examples of previously reported methods for DYKAT of diols and
this work.
1
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Chiral β-hydroxyketones (β-HKs) are commonly found in
nature,[15] for example as pheromone components of Sitona and
Sitophilus weevils.[15e-g] In addition, β-HKs constitute a class of
valuable building blocks, commonly employed in the total
synthesis of natural products, i. e. polyketides.[16] We envisioned
an effective epimerization mechanism for α-substituted β-
hydroxyketones with RuCl-complex II (Scheme 2a), including a
[1,5]-migration of ruthenium hydride species ([Ru]-H) between the
oxygen atoms of the 1,3-diketone moiety in intermediates int-A
and int-B as the key step (Scheme 2b). The transformation is
proposed to proceed via a non-chiral intermediate int-C. It has
been previously demonstrated during mechanistic studies on the
racemization of sec-alcohols with RuCl-complex II that the
substrate does not leave the coordination sphere of the metal
during the oxidation-reduction process.[17] In contrast, the use of
Ru-complex I under analogous reaction conditions would lead to
an equilibrium where the 1,3-diketone would readily dissociate
from the corresponding [Ru]-H moiety, which would in turn lead to
oxidation of the substrate.[18] Furthermore, an expected reaction
rate difference between the enzymatic acylation of syn- and anti-
diastereoisomers of α-substituted β-HKs would lead to formation
of highly useful diastereomerically enriched β-oxoacetates as
products.
yield of the desired product 2a in cyclohexane as the solvent after
20h at 80 C. The desired β-oxoacetate 2a was formed in 83%
o
yield, with a moderate diastereomeric ratio (dr) with a syn:anti
ratio of 30:70 (Table 1, entry 2). High enantiomeric excess (ee)
was observed, even though the formation of minor amounts of the
undesired enantiomer suggests that epimerization is not
sufficiently fast over the whole reaction course. Substrate
oxidation to give 3a as a byproduct occurred in measurable
amounts as a result of acceptorless dehydrogenation of 1a
catalyzed by Ru-complex Ia.[12] Use of solvents such as THF, DCE
or tBuOH in the reaction led to a considerable decrease of the
yield of 2a (Table 1, entries 3-5). Toluene was found to be the
best solvent in this transformation (Table 1, entry 6). Screening of
other racemization catalysts such as Ru-catalysts Ib and Ic led to
decreased yields of 2a, as well as lower ee values (Table1, entries
7-8).
To further improve the enantioselectivity of the reaction and
suppress occurring formation of the undesired oxidation product
3a, RuCl-complex II was tested as a racemization catalyst in this
reaction (Table 1, entry 9). Due to the superior epimerization
performance of catalyst II, the enzyme loading could be reduced
to half while retaining high yield and ee of 2a. The RuCl-complex
II was also found to be compatible with isopropenyl acetate as the
acyl donor (Table 1, entry 10), which facilitated the product
isolation. Under these optimized reaction conditions β-oxoacetate
2a was obtained in 90% isolated yield, 99% ee and syn:anti ratio
of 35:65 with no detected formation of 3a. We also tested the
performance of lipase PS-IM in the DYKAT of 1a (Table 1, entry
11). Under analogous reaction conditions after 64h reaction time
the β-oxoacetate 2a was obtained in 88% albeit with decreased
both dr and ee.
Table 1: Optimization of the reaction conditions.[a]
Entry
Ru-cat
[mol%]
CALB
[mg/
mmol]
40
solvent
[M]
2a
3a
syn-2a:
ee of
anti-2a
[%][c]
97
[%][b]
[%][b]
anti-2a
[c]
1
2
Ia (2.5)
Ia (2.5)
Ia (2.5)
Ia (2.5)
Ia (2.5)
Ia (2.5)
Ib (2.5)
Ic (2.5)
II (5.0)[d]
II (5.0)[d]
CyH
(0.2)
CyH
49
83
39
27
12
85
81
78
88
8
8
-
30:70
30:70
32:68
30:70
23:77
30:70
34:66
38:62
30:70
35:65
80
80
80
80
80
80
80
40
40
97
99
99
99
97
95
95
99
99
Scheme 2. a) Racemization pathways in the DYKAT of β-HKs employing Ru-
cat II. b) [1,5]-Migration of [Ru]-H as the key step in the racemization process.
(0.2)
THF
3
(0.2)
DCE
(0.2)
tBuOH
(0.2)
PhMe
(0.2)
PhMe
(0.2)
PhMe
(0.2)
PhMe
(0.2)
PhMe
(0.2)
We postulated that an increase of the steric demand of the
substituent in the α-position of the β-HKs would lead to improved
diastereoselectivity of the overall process. Initial attempts to
obtain a DYKAT of β-HKs indicated a significant drop in the rate
of the enzymatic acylation when α-substituted 3-hydroxy-5-
heptanones were used as substrates compared to that of 2-
4
-
5
8
10
5
5
-
6
hydroxy-4-pentanones. Hence, β-HK 1a bearing
a benzyl
7
substituent in the α-position was chosen as the standard
substrate in the optimization of the reaction conditions (Table 1).
Initially experiments were conducted employing Ru-
complex Ia as the racemization catalyst. p-Chlorophenyl acetate
was chosen as the acyl donor due to the observed increased
formation of the undesired diketone 3a when acyl donors such as
vinyl acetates were employed. An enzyme loading of 80 mg/mmol
of lipase CALB was found to be necessary for achieving good
8
9
10[e]
95
-
(90)[f]
2
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Entry
Ru-cat
[mol%]
CALB
[mg/
mmol]
-
solvent
[M]
2a
3a
syn-2a:
ee of
anti-2a
[%][c]
96
[%][b]
[%][b]
anti-2a
[c]
11[e,g]
II (5.0)[d]
PhMe
(0.2)
88
-
48:52
[a] Unless otherwise noted reactions were conducted under argon atmosphere
in the indicated solvent (1.0 mL) at 80 oC using 1a (0.2 mmol), p-ClPhOAc (1.5
equiv), Na2CO3 (1.5 equiv), Ru-cat (2.5-5 mol%), and CALB (indicated amount).
[b] Yield determined by 1H-NMR using mesitylene as the internal standard. [c]
dr and ee determined by GC on chiral stationary phase. [d] Using KOtBu (0.1 M
solution in toluene, 5 mol%) as an additive. [e] Using isopropenyl acetate (1.5
equiv) as the acyl donor. [f] Isolated yield. [g] Using lipase PS-IM (80 mg/mmol)
instead of CALB and the reaction time was 64h. DCE = 1,2-dichloroethane.
Scheme 3. Kinetic resolution (KR) of syn-1a and anti-1a (intermolecular
competition experiment). [a] Yield determined by 1H-NMR using mesitylene as
the internal standard. [b] dr and ee determined by GC on chiral stationary phase.
Next, the scope of the newly developed DYKAT reaction
was investigated (Scheme 4). Under the previously established
optimal reaction conditions (Conditions A), products 2a-c were
obtained in excellent yields, very high enantioselectivity and
moderate dr. However, β-HK 1d with n-butyl substituent in the α-
position led to dr of 45:55 (syn:anti) under these reaction
conditions. We speculate that the rate of enzymatic acylation of
1d is too fast for an efficient epimerization to occur by [1,5]-
migration of RuH. Hence, we further investigated if an increased
diastereomeric ratio of 2d could be achieved by lowering the
enzyme-to-catalyst ratio. After an additional screening of reaction
conditions (see the Supporting Information) new optimized
reaction conditions were established (Conditions B). We
observed that decreasing the amount of enzyme in the reaction
decreased the yield and increased the reaction time, whereas
raising the amount of catalyst to 7.5 mol% and diluting the
reaction mixture resulted in high yield of product 2d with increased
dr compared to with the previously used optimized conditions
(Conditions A). The newly optimized reaction conditions
(Conditions B) were further applied for substrates 1b, 1c, and 1e
in order to achieve higher dr of the corresponding products.
Substrate 1f containing a terminal alkyne moiety afforded the
corresponding β-oxoacetate 2f in 45% yield with moderate dr, but
decreased ee of both diastereoisomers. The yields of acetates 2g
and 2h obtained were low due to their instability under the
reaction conditions (they readily underwent elimination reactions
to form the corresponding α,β-unsaturated ketones as side
products). Higher enzyme loading and longer reaction times were
necessary to achieve efficient DYKAT of the 3-hydroxy-5-
heptanone-derived β-HKs 1i-k in good yields. Surprisingly, α-
methyl-substituted β-oxoacetate 2i showed a slight preference for
the syn-diastereomer, in contrast to the previous examples
described here. A plausible account for this observation is the way
that the β-HK adapts to the enzyme pocket, since the methyl
substituent is less sterically demanding than the propionyl moiety
in 2i. Introducing additional steric hindrance by creating a
quaternary stereogenic center in β-HK 1l caused an increased
enzyme demand. Even after prolonged reaction time, β-
oxoacetate 2l was obtained in low yield, with just marginally better
dr than 2a and decreased ee. Interestingly, cyclic β-HK 1m was
also found to be compatible with the newly developed DYKAT
protocol and afforded the corresponding β-oxoacetate 2m in 80%
yield and dr of 40:60 (syn:anti).
To gain further insight into the diastereoselectivity of the
enzymatic acylation reaction of 1a, the relative rates of the
formation of diastereomers syn-1a and anti-1a were measured.
First, a parallel experiment was carried out using syn-1a and anti-
1a as substrates (Figure 1). In this setting, alcohol anti-1a
undergoes acetylation to furnish anti-2a approximately twice as
fast as syn-1a.
Figure 1. Kinetic resolution (KR) of a) syn-1a and b) anti-1a (parallel experi-
ments). [a] Yield determined by 1H-NMR using mesitylene as the internal
standard.
Additionally, a competitive KR experiment was run, using
compound 1a with a starting diastereomeric ratio close to 1:1
syn:anti (Scheme 3). The faster reacting diastereomer
preferentially binds to the enzyme and thereby prevents access
of the slower reacting diastereomer, potentially amplifying the
diastereoselection. The competitive reaction indicates a relative
rate difference of 1:3 between syn- and anti-diastereoisomers,
due to the observed dr of the product 2a at low conversion.
3
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equiv), alcohol 4 (1.1 equiv) and CALB (80 mg/mmol). [a] Yield determined by
1H-NMR using 1,3,5-trimethoxybenzene as the internal standard. [b] dr and ee
determined by GC on chiral stationary phase.
In conclusion, we have reported the first protocol for
chemoenzymatic DYKAT of α-substituted β-HKs. The newly
developed method afforded highly useful β-oxoacetates as
products in good yields with high enantioselectivity and moderate
diastereoselectivity. The diastereoselectivity of the overall
process is proposed to be dependent on the rate difference of the
enzymatic acylation of syn- and anti-diastereomers of the β-HK
which is largely influenced by the steric demands of the
substituent in the α-position. While lipase CALB performed well
and afforded moderate to good dr of the target β-oxoacetates, the
use of lipase PS-IM led to considerable decrease of the
diastereoselectivity of the reaction. We expect, that future
improvements in terms of diastereoselectivity can be achieved by
the discovery of even more selective lipase enzymes in the near
future. Complimentary approach would be to use genetic tools like
directed evolution where the enzyme performance could be
specifically tailored to the described DYKAT protocol.
Acknowledgements
Financial support from the Swedish Research Council (2019-
04042), the Swedish Foundation for Strategic Environmental
Research (Mistra: project Mistra SafeChem, project number
2018/11), and the Crafoord Foundation is gratefully
acknowledged. Dr. Suresh Ganji is acknowledged for his kind
support of the project and Linnaeus University is acknowledged
for financial support to CRU.
Scheme 4. Scope of DYKAT of β-HKs. Unless otherwise noted the reaction was
conducted under argon atmosphere in anhydrous toluene (indicated amount) at
80 oC using 1 (0.2 mmol), Na2CO3 (1.0 equiv), Ru-cat II (indicated amount),
KOtBu (0.1 M solution in toluene, indicated amount) and CALB (40 mg/mmol).
[a] dr and ee determined by GC on chiral stationary phase. [b] 80 mg/mmol of
CALB was used. [c] 120 mg/mmol CALB. [d] Reaction time was 48h. [e]
Reaction time was 70h. [f] Reaction time was 90h.
Keywords: DYKAT • β-hydroxyketones • ruthenium • lipase •
racemization
[1]
[2]
[3]
E. N. Jacobsen, A. Pfaltz, H. Yamamoto, Comprehensive asymmetric
catalysis, Springer, Berlin, London, 1999.
As it was previously demonstrated, Ru-complex Ia can be
used to efficiently reduce ketones to alcohols via transfer
hydrogenation by the use of an external alcohol as a hydrogen
donor.[19] Herein we disclose a tandem hydrogenation-DYKAT of
1,3-diketone 3a as a one-pot procedure (Scheme 5). By
employing Ru-complex Ia as the racemization/transfer
hydrogenation catalyst, the mono reduction of the 1,3-diketone
moiety in 3a and subsequent epimerization of the in-situ
generated β-HK, the desired β-oxoacetate 2a was obtained in
65% NMR-yield with high enantiomeric excess.
P. Hoyos, V. Pace, A. R. Alcántara, Adv. Synth. Catal. 2012, 354, 2585-
2611.
a) H. Pellissier, Chirality from Dynamic Kinetic Resolution, Royal Society
of Chemistry, Cambridge, 2011. b) A. Kamal, M. A. Azhar, T. Krishnaji,
M. S. Malik, S. Azeeza, Coord. Chem. Rev. 2008, 252, 569-592.
M. T. El Gihani, J. M.J. Williams, Curr. Opin. Chem. Biol. 1999, 3, 11-15.
a) H. Pellisiier, Tetrahedron 2011, 67, 3769-3960. b) M. Xu, Z. Tan, C.
Zhu, W. Zhuang, H. Ying, P. Ouyang, Chin. J. Chem. Eng. 2021, 30, 146-
167.
[4]
[5]
[6]
For reviews on chemoenzymatic DKR of alcohols and amines see: a) O.
Pàmies, J.-E. Bäckvall, Chem. Rev. 2003, 103, 3247-3262. b) O. Verho,
J.-E. Bäckvall, J. Am. Chem. Soc. 2015, 137, 3996-4009. c) J. H. Lee, K.
Han, M.‐J. Kim, J. Park, Eur. J. Org. Chem. 2010, 2010, 999-1015. d) Z.
S.Seddigi, M. S.Malik, S. A. Ahmed, A. O. Babalghith, A. Kamale, Coord.
Chem. Rev. 2017, 348, 54-70.
[7]
[8]
a) B. Martín-Matute, M. Edin, K. Bogár, J.-E. Bäckvall, Angew. Chem.
Int. Ed. 2004, 43, 6535-6539. b) J. H. Choi, Y. K. Choi, Y. H. Kim, E. S.
Park, E. J. Kim, M.-J. Kim, J. Park, J. Org. Chem. 2004, 69, 1972-1977.
a) A. Petrenz-Beck, J. Kühn, R. Zuhse, M. B. Ansorge-Schumacher,
ChemistrySelect 2019, 4, 6469-6472. b) P. Ödman, L. A. Wessjohann,
U. T. Bornscheuer, J. Org. Chem. 2005, 70, 9551-9555. c) J. Cho, K.
Kim, J. Park, M.-J. Kim, Bull. Korean Chem. Soc. 2021, 42, 1028-1032.
a) Z. C. Litman, Y. Wang, H. Zhao, J. F. Hartwig, Nature 2018, 560, 355-
359. b) A. M. Sarkale, V. Maurya, S. Giri, C. Appayee, Org. Lett. 2019,
21, 4266-4270. c) M. A. Maskeri, M. L. Schrader, K. A. Scheidt, Chem.
[9]
Scheme 5. Tandem hydrogenation-DYKAT of 1,3-diketone 3a. The reaction
was conducted under argon atmosphere in anhydrous toluene (1 mL) at 80 oC
using 3a (0.2 mmol), Na2CO3 (1.0 equiv), Ru-cat Ia (5 mol%), p-ClPhOAc (1.5
4
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COMMUNICATION
Eur. J. 2020, 26, 5794-5798. For a review on cooperative chemo- and
biocatalysis see: M. Hönig, P. Sondermann, N. J. Turner, E. M. Carreira,
Angew. Chem. Int. Ed. 2017, 56, 8942-8973. For a review on bi-
enzymatic DKR see: M. M. Musa, Chirality 2020, 32, 147-157.
[10] a) K. Faber, Chem. Eur. J. 2001, 7, 5004-5010. b) B. M. Trost, Chem.
Pharm. Bull. 2002, 50, 1-14. For reviews on non-chemoenzymatic DKR
and DYKAT see: V. Bhat, E. R. Welin, X. Guo, B. M. Stoltz, Chem. Rev.
2017, 117, 4528-4561.
[11] a) M. Edin, J. Steinreiber, J.-E. Bäckvall, Proc. Natl. Acad. Sci. U.S.A.
2004, 101, 5761-5766. b) B. Martín-Matute, J.-E. Bäckvall, J. Org. Chem.
2004, 69, 9191-9195. c) K. Leijondahl, L. Borén, R. Braun, J.-E. Bäckvall,
J. Org. Chem. 2009, 74, 1988-1993. d) L. Borén, K. Leijondahl, J.-E.
Bäckvall, Tetrahedron Lett. 2009, 50, 3237-3240.
[12] B. A. Persson, A. L. E. Larsson, M. Le Ray, J.-E. Bäckvall, J. Am. Chem.
Soc. 1999, 121, 1645-1650.
[13] J. H. Choi, Y. H. Kim, S. H. Nam, S. T. Shin, M.-J. Kim, J. Park, Angew.
Chem. Int. Ed. 2002, 41, 2373-3276.
[14] a) B. Martín-Matute, M. Edin, K. Bogár, J.-E. Bäckvall, Angew. Chem.
Int. Ed. 2004, 43, 6535-6539. b) B. Martín-Matute, M. Edin, K. Bogár, F.
B. Kaynak, J.-E. Bäckvall, J. Am. Chem. Soc. 2005, 127, 8817-8825. c)
M. Edin, B. Martín-Matute, J.-E. Bäckvall, Tetrahedron: Asymmetry
2006, 17, 708-715. d) B. Martín-Matute, M. Edin, J.-E. Bäckvall, Chem.
Eur. J. 2006, 12, 6053-6061.
[15] a) H. Choe, T. T. Pham, J. Y. Lee, M. Latif, H. Park, Y. K. Kang, J. Lee,
J. Org. Chem. 2016, 81, 2612-2617. b) D. Enders, O. Niemeier, L.
Straver, Synlett 2006, 3399-3402. c) S. Hess, M. E. Maier,
ChemistrySelect 2020, 5, 7315-7319. d) B. Zhu, J. S. Panek, Org. Lett.
2000, 2, 2575-2578. e) B. Bohman, C.R. Unelius, Tetrahedron, 2009, 65,
8697-8701. f) B. Bohman, L. R. Cavonius, C.R. Unelius, Green Chem.,
2009, 11, 1900-1905. g) N. R. Schmuff, J. K. Phillips, W. E. Burkholder,
H. M. Fales, C.-W. Chen, P. P. Roller, M. Ma, Tetrahedron Lett., 1984,
25, 1533-1534.
[16] a) I. Paterson, D. Y. Chen, J. L. Aceña, A. S. Franklin, Org. Lett. 2000, 2,
1513-1516. b) L. C. Dias, C. da Costa S. Gonçalves, Adv. Synth. Catal.
2008, 350, 1017-1021. c) F. Eustache, P. I. Dalko, J. Cossy, Tetrahedron
Lett. 2003, 44, 8823-8826. d) C. R. Unelius, K.-C. Park, M. McNeill, S. L.
Wee, B. Bohman, D. M. Suckling, Naturwissenschaften 2013, 100, 135-
143. e) D. Kalaitzakis, J. D. Rozzell, S. Kambourakis, I. Smonou, Eur. J.
Org. Chem. 2006, 10, 2309-2313.
[17] B. Martín-Matute, J. B. Åberg, M. Edin, J.-E. Bäckvall, Chem. Eur. J.
2007, 13, 6063-6072.
[18] B. Martín-Matute, J.-E. Bäckvall, J. Org. Chem. 2004, 69, 9191-9195.
[19] a) R. L. Chowdhury, J.-E. Bäckvall, J. Chem. Soc., Chem. Commun.
1991, 1063-1064. b) O. Pàmies, J.-E. Bäckvall, Chem. Eur. J. 2001, 7,
5052-5058. c) Jung, Koh, Kim, Park, Org. Lett. 2000, 2, 409-411. d) H.
M. Jung, J. H. Koh, M. J. Kim, J. Park, Org. Lett. 2000, 2, 2487-2490. For
a review on transition metal-catalyzed hydrogen transfer reactions see:
J. S. M. Samec, J.-E Bäckvall, P. G. Andersson, P. Brandt, Chem. Soc.
Rev. 2006, 35, 237-248. For a review on the applications of Ru-complex
I see: B. L. Conley, M. K. Pennington-Boggio, E. Boz, T. J. Williams,
Chem. Rev. 2010, 110, 2294-2312.
5
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10.1002/chem.202102683
Chemistry - A European Journal
COMMUNICATION
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Ruthenium and enzyme catalysis were combined in a one-pot procedure to achieve efficient DYKAT of α-substituted β-hydroxyketones.
This newly developed protocol offers straightforward access to enantiomerically pure and diastereomerically enriched β-oxoacetates
in high yields by employing a ruthenium-based racemization catalyst for efficient racemization-epimerization of substrates via formation
of non-chiral 1,3-diketone intermediates.
Institute and/or researcher Twitter usernames: @BackvallJEB_grp
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This article is protected by copyright. All rights reserved.