Enantioselective route to ketones and lactones from exocyclic allylic alcohols via metal and enzyme catalysis

Article abstract of DOI:10.1021/ol302358j

A general and efficient route for the synthesis of enantiomerically pure α-substituted ketones and the corresponding lactones has been developed. Ruthenium- and enzyme-catalyzed dynamic kinetic resolution (DKR) with a subsequent Cu-catalyzed α-allylic substitution are the key steps of the route. The α-substituted ketones were obtained in high yields and with excellent enantiomeric excess. The methodology was applied to the synthesis of a naturally occurring caprolactone, (R)-10-methyl-6-undecanolide, via a subsequent Baeyer-Villiger oxidation.

Full text of DOI:10.1021/ol302358j

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Enantioselective Route to Ketones and
Lactones from Exocyclic Allylic Alcohols
via Metal and Enzyme Catalysis
ꢀ
Madeleine C. Warner, Anuja Nagendiran, Krisztian Bogar,* and Jan-E. Backvall*
ꢀ
€
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University,
SE-106 91 Stockholm, Sweden
jeb@organ.su.se; krisztian@organ.su.se
Received August 23, 2012
ABSTRACT
A general and efficient route for the synthesis of enantiomerically pure R-substituted ketones and the corresponding lactones has been
developed. Ruthenium- and enzyme-catalyzed dynamic kinetic resolution (DKR) with a subsequent Cu-catalyzed R-allylic substitution are the key
steps of the route. The R-substituted ketones were obtained in high yields and with excellent enantiomeric excess. The methodology was applied
to the synthesis of a naturally occurring caprolactone, (R)-10-methyl-6-undecanolide, via a subsequent BaeyerꢀVilliger oxidation.
Ketones and lactones not only are very useful building
blocks but also represent structural motifs in a variety of
natural products.1 These natural products have attracted
considerable attention because of their biological and
medicinal properties.2 Most of them have substituents in
various positions on the ring, which makes them chiral,
and this chirality determines their biological activity. For
this reason, many methods have been developed to prepare
chiral lactones, such as synthesis via chiral auxiliaries3
and enantioselective variants of catalytic BaeyerꢀVilliger
oxidations,4 CꢀH insertion reactions,5 hydrogenations,6
1,4-reduction7 and 1,4-addition reactions,8 metal-catalyzed
cyclization reactions,9 and biocatalytic reactions.10
(3) (a) Koch, S. S. C.; Chamberlin, A. R. J. Org. Chem. 1993, 58,
2725–2737. (b) de L. Vanderlei, J. M.; Coelho, F.; Almeida, W. P. Synth.
Commun. 1998, 28, 3047. (c) Nair, V.; Prabbakaran, J.; George, G. T.
Tetrahedron 1997, 53, 15061–15068.
(4) (a) Uchida, T.; Katsuki, T.; Ito, K.; Akashi, S.; Ishii, A.; Kuroda,
T. Helv. Chim. Acta 2002, 85, 3078–3089. (b) Murahashi, S.-I.; Ono, S.;
Imada, Y. Angew. Chem., Int. Ed. 2002, 41, 2366. (c) Frison, J.-C.;
Palazzi, C.; Bolm, C. Tetrahedron 2006, 62, 6700–6706.
(1) Tomioka, K.; Koga, K. In Asymmetric Synthesis; Morrison, J. D.,
Ed.; Academic Press: New York, 1983; Vol. 2, pp 201ꢀ224. (b) Enders, D.
In Asymmetric Synthesis; Morrison, J. D., Ed.; Academic Press: New York,
1983; Vol. 3, pp 275ꢀ334. (c) Mulzer, J. In Synthesis of Esters, Activated
Esters and Lactones; Trost, B. M., Fleming, I., Eds.; Comprehensive
Organic Synthesis; Pergamon Press: Oxford, 1991; Vol. 6, pp 323ꢀ380.
(d) Culkin, D. A.; Hartwig, J. F. Acc. Chem. Res. 2003, 36, 234–245.
(e) Tsuji, J. Palladium in Organic Synthesis; Topics in Organometallic
Chemistry Series; Springer: Berlin, Germany, 2005; Vol. 14, p 259. (f) Scott,
N. M.; Nolan, S. P. N-Heterocyclic Carbenes in Synthesis; Nolan, S. P.,
Ed.; Wiley-VCH: Weinheim, Germany, 2006; pp 63ꢀ64.
(5) (a) Bode, J. W.; Doyle, M. P.; Protopopova, M. N.; Zhou, Q.-L.
J. Org. Chem. 1996, 61, 9146–9155. (b) Anada, M.; Hashimoto, S.-i.
Tetrahedron Lett. 1998, 39, 79–82.
(6) (a) Benincori, T.; Rizzo, S.; Pilati, T.; Ponti, A.; Sada, M.;
ꢁ
Pagliarini, E.; Ratti, S.; Guiseppe, C.; de Ferra, L.; Sannicolo, F.
Tetrahedron: Asymmetry 2004, 15, 2289–2297. (b) Ohkuma, T.; Kitamura,
M.; Noyori, R. Tetrahedron Lett. 1990, 31, 5509–5512. (c) Ojima, I.;
Kogure, T.; Kumagai, M. J. Org. Chem. 1977, 42, 1671–1679.
(7) Hughes, G.; Kimura, M.; Buchwald, S. L. J. Am. Chem. Soc.
2003, 125, 11253–11258. (b) Lipshutz, B. H.; Servesko, J. M.; Taft, B. R.
J. Am. Chem. Soc. 2004, 126, 8352–8353.
(2) For instance: (a) Ayreas, D. C.; Loike, J. D. Chemistry &
Pharmacology of Natural Products. Lignans, Chemical, Biological and
Clinical Properties; Cambridge University Press: New York, 1990. (b) Li,
N.; Wu, J. L.; Sakai, J. I.; Ando, M. J. Nat. Prod. 2003, 66, 1421–1426.
(c) Usia, T.; Watabe, T.; Kadota, S.; Tesuka, Y. J. Nat. Prod. 2005, 68,
64–68.
r
10.1021/ol302358j
XXXX American Chemical Society

From a green chemistry point of view, enzyme-catalyzed
kinetic resolution (KR) of a racemate has proved to be a
convenient method to obtain enantiomerically enriched
materials.11 Although lipase-catalyzed resolutions seem to
be ideal in both academic and industrial applications, they
can only provide the desired enantiomerically enriched
product in a maximum theoretical yield of 50%. This
limitation can be overcome in dynamic kinetic resolution
(DKR) in which the enzyme-mediated enantioselective
transformation is integrated with an in situ racemization
of the starting material, usually by a metal.12 Since the fast-
reacting enantiomer is never depleted from the reaction
mixture, a theoretical yield of 100% can be obtained and
this makes DKR a powerful tool for the preparation of
enantiomerically enriched compounds in high yields. Over
the past decade, we have developed highly efficient DKR
protocols for secondary12c and primary alcohols13 as well
as for amines,14 and in some cases we have demonstrated
synthetic applications toward biologically interesting com-
pounds.14a,15 Recently we reported on an efficient DKR
for cyclic and acyclic allylic alcohols, utilizing ruthenium
catalyst 1 for the racemization and Candida antarctica
lipase B (CALB) or Subtilisin Carlsberg for the enzymatic
kinetic resolution.16 Both (R)- and (S)-acetates could be
obtained with high enantiopurity and in high yields de-
pending on the enzyme applied.
Here we wish to report on a general route for the
enantioselective synthesis of R-alkylated cyclic ketones
and their corresponding lactones, utilizing DKR in the
enantiodetermining step. Our synthetic strategy begins
with DKR of the exocyclic allylic alcohols (I), with the
use of ruthenium catalyst 1 and CALB, producing the
corresponding allylic esters (II). Subsequent Cu-catalyzed
allylic R-substitution proceeds with inversion of the stereo-
chemistry and forms alkenes (III). Further oxidative clea-
vage of the CdC bond releases the hidden ketone
functionality (IV). Finally, BaeyerꢀVilliger oxidation pro-
duces the enantiomerically pure lactones (V) (Scheme 1).
(8) (a) Takaya, Y.; Senda, T.; Kurushima, H.; Ogasawara, M.;
Hayashi, T. Tetrahedron: Asymmetry 1999, 10, 4047–4056. (b) Kina,
A.; Ueyama, K.; Hayashi, T. Org. Lett. 2005, 7, 5889–5892. (c) Kurihara,
K.; Sugishita, N.; Oshita, K.; Piao, D.; Yamamoto, Y.; Miyaura, N.
J. Organomet. Chem. 2007, 692, 428–435.
(9) For instance: (a) Pd-catalyzed oxidative cyclization: Trend,
R. M.; Ramtohul, Y. K.; Ferreira, E. M.; Stoltz, B. Angew. Chem.,
Int. Ed. 2003, 42, 2892–2895. (b) Au-catalyzed cyclization: Genin, E.;
Toullec, P. Y.; Antoniotti, S.; Brancour, C.; Genet, J.-P.; Michelet, V.
J. Am. Chem. Soc. 2006, 128, 3112–3113. (c) AgOTf-catalyzed intramo-
lecular additions of hydroxyl or carbonyl gropus to olefins: Yang,
C.-G.; Reich, N. W.; Shi, Z.; He, C. Org. Lett. 2005, 7, 4553–4556.
(10) Enzymatic resolution: (a) Forzato, C.; Gandolfi, R.; Molinari,
F.; Nitti, P.; Pitacco, G.; Valentin, E. Tetrahedron: Asymmetry 2001, 12,
1039–1046. (b) Brenna, E.; Negri, C. D.; Fuganti, C.; Serra, S. Tetra-
hedron: Asymmetry 2001, 12, 1871–1879. (c) Shimotori, Y.; Miyakoshi,
T. Synth. Commun. 2009, 39, 1570–1582.
Scheme 1. Synthetic Strategy Toward Enantioenriched
R-Alkylated Ketones (IV) and Lactones (V) via Tandem
DKR and Cu-Catalyzed Allylic Substitution (n = 1, 2)
(11) (a) Ghanem, A.; Aboul-Enein, H. Y. Tetrahedron: Asymmetry
2004, 15, 3331–3351. (b) Bornscheuer, U. T.; Kazlauskas, R. J. Hydrolases
in Organic Synthesis: Regio- and Stereoselective Biotransformations, 2nd ed.;
Wiley-VCH: Weinheim, 2005. (c) Faber, K. Biotransformations in Organic
Synthesis, 6th ed.; Springer: 2011.
€
(12) (a) Sturmer, R. Angew. Chem., Int. Ed. Engl. 1997, 36, 1173–
€
1174. (b) Larsson, A. L. E.; Persson, B. A.; Backvall, J.-E. Angew.
Chem., Int. Ed. Engl. 1997, 36, 1211–1212. (b) Martın-Matute, B.; Edin,
M.; Bogar, K.; Backvall, J.-E. Angew. Chem., Int. Ed. 2004, 43, 6535–
´
ꢀ
€
ꢀ
6539. (c) Martın-Matute, B.; Edin, M.; Bogar, K.; Kaynak, F. B.;
´
€
Backvall, J.-E. J. Am. Chem. Soc. 2005, 127, 8817–8825. (c) Choi,
J. H.; Kim, Y.-H.; Nam, S. H.; Shin, S. T.; Kim, M.-J.; Park, J. Angew.
Chem., Int. Ed. 2002, 41, 2373–2376. (d) Noyori, R.; Tokunaga, M.;
Kitamura, M. Bull. Chem. Soc. Jpn. 1995, 68, 36–56. (e) Bouzemi, N.;
Aribi-Zouioueche, L.; Fiaud, J.-C. Tetrahedron: Asymmetry 2006, 17,
€
´
n-Matute, B.; Backvall, J.-E. Curr. Opin. Chem. Biol.
797–800. (f) Martı
The cyclic allylic alcohol substrates 2a and 2b were
synthesized by a straightforward two-step procedure (see
Supporting Information for further details). Subsequent
DKR of 2a and 2b was performed according to the
previously published procedure (Table 1).16 Both acylated
products (R)-3a and (R)-3b were obtained in good isolated
yields and excellent ee (>99%) using ruthenium catalyst
1 and Candida antarctica lipase B (CALB). A slightly
€
n-Matute; J.-E. Backvall, Dynamic
2007, 11, 226–232. (g) B. Martı
´
Kinetic Resolution. In Asymmetric Organic Synthesis with Enzymes;
Gotor, V.; Alfonso, I.; Garcia-Urdiales, E., Eds.; Wiley-VCH: Weinheim,
€
Germany, 2008; pp 89ꢀ113. (h) Martı
´
n-Matute, B.; Backvall, J.-E.
Chemoenzymatic Deracemization Processes. In Organic Synthesis with
Enzymes in Non-Aqueous Media; Carrea, G., Riva, S., Eds.; Wiley-VCH:
Weinheim, Germany, 2008: pp 113ꢀ144. (i) Ahn, Y.; Ko, S.-B.; Kim,
M.-J.; Park, J. Coord. Chem. Rev. 2008, 252, 647–658.
€
€
(13) Strubing, D.; Krumlinde, P.; Piera, J.; Backvall, J.-E. Adv.
Synth. Catal. 2007, 349, 1577–1581.
ꢀ
(14) (a) Thalen, L. K.; Zhao, D.; Sortais, J. B.; Paetzold, J.; Hoben,
€
C.; Backvall, J. E. Chem.;Eur. J. 2009, 15, 3403–3410. For work by
ꢀ ꢀ ꢀ €
(16) (a) Bogar, K.; Vidal, P. H.; Alcantara Leon, A. R.; Backvall,
others, see: (b) Kim, M.-J.; Kim, W.-H.; Han, K.; Choi, Y. K.; Park, J.
Org. Lett. 2007, 9, 1157–1159. (c) Gastaldi, S.; Escoubet, S.; Vanthuyne,
N.; Gil, G.; Bertrand, M. P. Org. Lett. 2007, 9, 837–839. (d) Parvulescu,
A. N.; Jacobs, P. A.; De Vos, D. E. Chem.;Eur. J. 2007, 13, 2034–2043.
(e) Parvulescu, A. N.; Jacobs, P. A.; De Vos, D. E. Appl. Catal. A:
General 2009, 368, 9–16.
ꢀ
ꢀ
J.-E. Org. Lett. 2007, 9, 3401–3404. (b) Thalen, L. K.; Sumic, A.; Bogar,
€
K.; Norinder, J.; Persson, A. K. A.; Backvall, J.-E. J. Org. Chem. 2010,
75, 6842–6847.
(17) (a) Fourquet, M.; Schlosser, M. Angew. Chem., Int. Ed. 1974, 13,
82–83. (b) Tseng, C. C.; Paisley, S. D.; Gering, H. L. J. Org. Chem. 1986,
€ ꢀ
51, 2884–2891. (c) Backvall, J.-E.; Sellen, M.; Grant, B. J. Am. Chem.
€
ꢀ
€
ꢀ
(15) (a) Traff, A.; Bogar, K.; Warner, M.; Backvall, J.-E. Org. Lett.
€
€
2008, 10, 4807–4810. (b) Krumlinde, P.; Bogar, K.; Backvall, J.-E.
J. Org. Chem. 2009, 74, 7407–7410. (c) Krumlinde, P.; Bogar, K.;
Soc. 1990, 112, 6615–6621. (d) Meuzelaar, G. J.; Karlstrom, A. S. E.; van
ꢀ
€
Klaveren, M.; Persson, E. S. M.; del Villar, A.; van Koten, G.; Backvall,
€
Backvall, J.-E. Chem.;Eur. J. 2010, 16, 4031–4036. (d) Norinder, J.;
J.-E. Tetrahedron 2000, 56, 2895–2903. (e) Ito, M.; Matsuumi, M.;
Murugesh, M. G.; Kobayashi, Y. J. Org. Chem. 2001, 66, 5881–5889.
ꢀ
€
Bogar, K.; Kanupp, L.; Backvall, J.-E. Org. Lett. 2007, 9, 5095–5098.
ꢀ
€
€
€
(e) Johnston, E. V.; Bogar, K.; Backvall, J.-E. J. Org. Chem. 2010, 75,
(f) Karlstrom, A. S. E.; Backvall, J.-E. In Modern Organocopper
Chemistry; Krause, N., Ed.; Wiley-VCH: Weinheim, Germany, 2002;
pp 259ꢀ288.
€
€
4596–4599. (f) Traff, A. M.; Lihammar, R.; Backvall, J.-E. J. Org. Chem.
2011, 76, 3917–3921.
B
Org. Lett., Vol. XX, No. XX, XXXX

elevated temperature (40 °C) was required to increase the
rate of the reaction.
Table 2. Cu-Catalyzed Allylic Substitution Reaction
Copper-catalyzed allylic substitution reactions with
Grignard reagents are well studied and can proceed
via two different pathways, producing either the R- or
γ-alkylated product (Scheme 2).17ꢀ19 It is generally ac-
cepted that the oxidative addition to allylic esters by Cu(I)
proceeds with high γ-regioselectivity, forming σ-allyl com-
plex 4.17b,c The latter reaction proceeds with anti stereo-
chemistry. Fast reductive elimination from intermediate 4
would result in formation of the γ-alkylated product 5 via
an SN20 pathway. However, if rearrangement of complex 4
to R-allyl copper complex 6 is faster, product III will be
entrya substrate
RMgX
MeMgBr
product yield (%)b
1
2
3
4
(R)-3a
(R)-3a
(R)-3a
(R)-3a
(S)-7a
(S)-8a
(S)-9a
86
64
88
EtMgBr
PhMgBr
4-MeOC6H4MgBr
(S)-10a 86 (R:γ =
90:10)
Table 1. DKR of Allylic Alcohols 2a and 2b
5
6
(R)-3a
(R)-3a
CH3(CH2)4MgBr
(S)-11a
82
(CH3)2CH(CH2)3MgBr (S)-12a 76 (R:γ =
81:19)
7
(R)-3b
MeMgBr
(S)-7b
74 (R:γ =
65:35)
75
8
9
(R)-3b
(R)-3b
PhMgBr
(S)-9b
CH3(CH2)4MgBr
(S)-11b
76 (R:γ =
74:26)
10
(R)-3b
(CH3)2CH(CH2)3MgBr (R)-12bc 78 (R:γ =
entrya
substrate
conv (%)b
yield (%)c
ee (%)d
77:23)
a The substrate was added to a solution of RMgX (2.5 equiv) and
CuCl (20 mol %) in dry THF at 0 °C. b Isolated yields. The R:γ ratio was
determined by 1H NMR. In the cases not indicated the reactions were
R-selective (>97% R). c (S) changes to (R) because of the sequential rule.
1
2
2a
2b
>99
>99
76
84
>99
>99
a 2.0 mmol of 2, 64 mg of Ru-catalyst 1 (5 mol %), 12 mg of CALB,
5 mol % of t-BuOK, 2 mmol of Na2CO3, and 3.0 mmol of isopropenyl
acetate in dry toluene (4.0 mL) under argon for 48 h. b Determined by 1H
NMR. c Isolated yield. d Determined by chiral HPLC.
Different conditions for the Cu-catalyzed allylic sub-
stitution were screened using a previously published
procedure.19 Some initial optimization was performed
withrac-(3b) and commerciallyavailable Grignard reagent
MeMgBr. With 1.5 equiv of MeMgBr and 20 mol % of
CuCl in dry THF, 35% of the desired product 7b was
formed. Some attack on the ester function in 3b forming 2b
was observed (15%) under these conditions. Also, 50% of
unreacted starting material 3 was observed. When THF
was exchanged for Et2O as solvent, the reaction was much
slower and only 4% of the desired product 7b was formed.
Also increased attack on the ester seemed to occur in Et2O
compared to THF. Therefore, THF was chosen as the
solvent.
formed via an SN2 pathway. Intermediate 4 will also be in
equilibrium with the rotamer 40. If the equilibrium between
rotamers 4 and 40 is fast, this would result in a mixture of
products III and III0. Products III and III0 are diastereo-
isomers, and therefore the ratio between them will be deter-
mined by the CurtinꢀHammet principle. In this synthetic
approach, selective R-substitution was desired producing
product III with retained chiral information (Scheme 2).
Scheme 2. Different Pathways for the Cu-Catalyzed Allylic
Substitution (n = 1, 2)
Therefore, instead of adding the Grignard reagent to the
substrate mixed with the copper salt we argued that it
would be better to first let the Grignard reagent react with
the CuCland thenadd the substrate, in ordertoensure that
only dialkylcuprate is present in the solution. This is
expected to result in better conversion. The allylic sub-
stitution reactions were performed in this manner on the
DKR products (R)-3a and (R)-3b with different Grignard
reagents (Table 2). The Cu-catalyzed allylic substitution
reactions proceeded well with moderate to high isolated
(18) (a) Yamanaka, M.; Kato, S.; Nakamura, E. J. Am. Chem. Soc.
2004, 126, 6287–6293. (b) Yoshikai, N.; Zhang, S.-L.; Nakamura, E.
J. Am. Chem. Soc. 2008, 130, 12862–12863.
€
(19) Norinder, J.; Backvall, J.-E. Chem.;Eur. J. 2007, 13, 4094–
4102.
Org. Lett., Vol. XX, No. XX, XXXX
C

Table 3. Oxidative Cleavage of the CdC Bond
Scheme 3. Synthesis of (R)-10-Methyl-6-undecanolide ((R)-17)
(R)-10-Methyl-6-undecanolide ((R)-17) is a caprolactone
recently isolated from a marine streptomycete (isolate
B6007).21 This caprolactone has shown promising activity
against different human cancer cell lines such as inhibition
of the cell growth of HM02 (gastric adenocarcinoma),
HepG2 (hepatocellular carcinoma), and MCF7 (breast
adenocarcinoma), with concomitant low general cytotoxicity.21
As a synthetic application ketone, (R)-16b was transformed
to the lactone derivative (R)-17 in a BaeyerꢀVilliger oxida-
tion with m-CPBA (Scheme 3). (R)-17 was isolated by flash
chromatography in 90% yield and with excellent enantio-
meric excess (>99% ee) in comparison with previously
published data (95% ee).22
In conclusion we have developed a general and efficient
route toward enantioselective synthesis of R-alkylated
cyclic ketones and the corresponding lactones. This was
done via ruthenium- and enzyme-catalyzed DKR of allylic
alcohol substrates and subsequent Cu-catalyzed R-allylic
substitution. The methodology was applied to the synthe-
sis of a natural product, caprolactone (R)-17.
entrya n substrate
R
product yield (%)b ee (%)
1
2
3
4
5
1
1
1
2
2
(S)-7a
(S)-8a
Me
Et
(S)-13a
(S)-14a
(R)-15a
(R)-15b
69c
74
89
73
82
94d
>99e
97e
98d
>99f
(S)-11a Ph
(S)-11b Ph
(R)-12b (CH3)2CH(CH2)3 (R)-16b
a NaIO4 (5 equiv) and RuCl3 xH2O (ca. 1 mol %) were added to the
3
substrate dissolved in a 1:1:2 DCM/CH3CN/H2O mixture at rt. b Iso-
lated yields except for entry 1. c Yield determined by GC. d Determined
by chiral GC. e Determined by chiral HPLC. f Determined by chiral GC
after transformation to the lactone derivative.
yields. For the more electron-rich and sterically hindered
Grignard reagents some of the γ-alkylated products were
observed. The R/γ product ratio was found to be slightly
better for the five-membered substrate (R)-3a (Table 2).
The synthetic utility of the Cu-catalyzed allylic substitu-
tion reaction was demonstrated by transformation of
selected products from Table 2 to the corresponding
ketone derivatives (Table 3). Oxidative cleavage of the
CdC double bond was performed with NaIO4 using
Acknowledgment. Financial support from the Swedish
Research Council, Knut and Alice Wallenberg Foundation,
and Berzelii Center EXSELENT is gratefully acknowl-
edged. We thank Novozymes A/S for a gift of CALB.
RuCl3 xH2O as the catalyst.16,20 The ketones were iso-
3
lated by column chromatography in high yields. A few
percent lossineewas observed in somecases. Thereactions
were quenched at nearly full conversion affording the
products (R)-15a and (R)-15b with 97 and 98% ee, respec-
tively (Table 3, entries 3 and 4). No racemization was
observed for substrates (S)-14a and (R)-16b (Table 3,
entries 2 and 5).
Supporting Information Available. Description of ex-
perimental procedures and full characterization of new
compounds. This material is available free of charge via
the Internet at http://pubs.acs.org.
(22) Soorukram, D.; Knochel, P. Angew. Chem., Int. Ed. 2006, 45,
3686–3689.
(20) Carlsen, P. H. J.; Katsuki, T.; Sharpless, K. B. J. Org. Chem.
1981, 46, 3936–3938.
(21) Strizke, K.; Schulz, S.; Laatsch, H.; Helmke, E.; Beil, W. J. Nat.
The authors declare no competing financial interest.
Prod. 2004, 67, 395–401.
D
Org. Lett., Vol. XX, No. XX, XXXX