Organic Letters
Letter
a
Table 1. Other Substrates
AUTHOR INFORMATION
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Corresponding Author
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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E. Rideau (Oxford Chemistry) is acknowledged for stimulating
discussions and valuable assistance. K.G. is supported by EPSRC
Centre for Doctoral Training in Synthesis for Biology and
Medicine (EP/L015838/1). S.P.F. is supported by the EPSRC
(EP/M002144/1, EP/M025241/1, EP/N022246/1).
REFERENCES
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(1) Blunt, J. W.; Copp, B. R.; Hu, W.-P.; Munro, M. H. G.; Northcote,
P. T.; Prinsep, M. R. Nat. Prod. Rep. 2007, 24, 31−86.
(2) For example: (a) Afinitor (everolimus), Novartis; (b) Advair
Diskus (fluticasone propionate), GSK; (c) Vyvanse (lisdexamfetamine),
Shire Pharmaceuticals Group; (d) Symbicort (budesonide), AstraZe-
neca; (e) Xeloda (capecitabine), Roche.
(3) Copper-Catalyzed Asymmetric Synthesis; Alexakis, A., Krause, N.,
Woodward, S., Eds.; Wiley-VCH: Weinheim, 2014.
́ ́
(4) Mauduit, M.; Basle, O.; Clavier, H.; Crevisy, C.; Denicourt-
Nowicki, A. Comprehensive Organic Synthesis II; Elsevier, 2014.
(5) Harutyunyan, S. R.; den Hartog, T.; Geurts, K.; Minnaard, A. J.;
Feringa, B. L. Chem. Rev. 2008, 108, 2824−2852.
a
b
Reactions performed on 0.4 mmol scale. Conditions C: Cp2ZrMeCl
(2.5 equiv), L2 (22 mol %), CuCl (0.20 equiv), AgOTf (0.20 equiv),
TMSCl (5.0 equiv), 5:1 Et2O/CH2Cl2, 0 °C, 15 h. Conditions D:
Cp2ZrMeCl (1.6 equiv), L3 (10 mol %), CuCl (0.10 equiv), AgOTf
(0.11 equiv), TMSCl (5.0 equiv), 5:1 Et2O/CH2Cl2, 0 °C, 45 min.
Conditions E: Cp2ZrMeCl (1.6 equiv), ent-L1 (10 mol %), CuCl (0.10
equiv), AgOTf (0.11 equiv), TMSCl (5.0 equiv), 1:1 Et2O/CH2Cl2, rt,
15 h. Conditions F: Cp2ZrMeCl (1.6 equiv), L1 (10 mol %), CuI
(6) Alexakis, A.; Backvall, J.-E. E.; Krause, N.; Pam
̀
ies, O.; Dieg
́
uez, M.
̈
Chem. Rev. 2008, 108, 2796−2823.
(7) Hawner, C.; Alexakis, A. Chem. Commun. 2010, 46, 7295.
(8) D’Augustin, M.; Palais, L.; Alexakis, A. Angew. Chem., Int. Ed. 2005,
44, 1376−1378.
(9) Endo, K.; Hamada, D.; Yakeishi, S.; Shibata, T. Angew. Chem., Int.
Ed. 2013, 52, 606−610.
c
(0.10 equiv), CDCl3, rt, 15 h. Isolated yield unless stated otherwise.
d
e
f
Determined by chiral HPLC. Volatile product. Determined by
g
h
chiral GC. Pure major isomer only. NMR yield against internal
standard. Determined by chiral GC analysis of epoxidised crude
mixture of 16.
(11) Yamazaki, S.; Yamabe, S. J. Org. Chem. 2002, 67, 9346−9353.
(12) Lopez, F.; Harutyunyan, S. R.; Minnaard, A. J.; Feringa, B. L. J.
́
i
Am. Chem. Soc. 2004, 126, 12784−12785.
(13) Des Mazery, R.; Pullez, M.; Lop
́
ez, F.; Harutyunyan, S. R.;
a,b
Scheme 5. Synthesis of Natural Muscone
Minnaard, A. J.; Feringa, B. L. J. Am. Chem. Soc. 2005, 127, 9966−9967.
(14) Howell, G. P.; Fletcher, S. P.; Geurts, K.; ter Horst, B.; Feringa, B.
L. J. Am. Chem. Soc. 2006, 128, 14977−14985.
(15) ter Horst, B.; Feringa, B. L.; Minnaard, A. J. Org. Lett. 2007, 9,
3013−3015.
(16) Wang, S.-Y.; Loh, T.-P. Chem. Commun. 2009, 46, 8694−8703.
(17) Wang, S.-Y.; Lum, T.-K.; Ji, S.-J.; Loh, T.-P. Adv. Synth. Catal.
2008, 350, 673−677.
a
b
Isolated yield. ee determined by GC analysis of crude material
reduced to the corresponding alcohols.
́ ́
(18) Drissi-Amraoui, S.; Morin, M. S. T.; Crevisy, C.; Basle, O.; Marcia
de Figueiredo, R.; Mauduit, M.; Campagne, J. Angew. Chem., Int. Ed.
2015, 54, 11830−11834.
scale in our laboratory, and presumably this scale can be
increased. The reagent is a readily manipulated crystalline
powder that can be weighed out in air and is stable for at least 6
months when stored on the bench under inert gas.
Ongoing studies in our laboratory aim to expand the range of
asymmetric reactions alkyl zirconocene species can be used in
and will be reported in due course.
(19) Roth, P. M. C.; Fletcher, S. P. Org. Lett. 2015, 17, 912−915.
(20) Sidera, M.; Roth, P. M. C.; Maksymowicz, R. M.; Fletcher, S. P.
Angew. Chem., Int. Ed. 2013, 52, 7995−7999.
(21) Roth, P. M. C.; Sidera, M.; Maksymowicz, R. M.; Fletcher, S. P.
Nat. Protoc. 2013, 9, 104−111.
(22) Rideau, E.; Masing, F.; Fletcher, S. P. Synthesis 2015, 47, 2217−
̈
2222.
(23) Maksymowicz, R. M.; Roth, P. M. C.; Fletcher, S. P. Nat. Chem.
2012, 4, 649−654.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
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S
(24) Maksymowicz, R. M.; Sidera, M.; Roth, P.; Fletcher, S. P. Synthesis
2013, 45, 2662−2668.
(25) Maciver, E. E.; Maksymowicz, R. M.; Wilkinson, N.; Roth, P. M.
C.; Fletcher, S. P. Org. Lett. 2014, 16, 3288−3291.
(26) Caprioglio, D.; Fletcher, S. P. Chem. Commun. 2015, 51, 14866−
14868.
All procedures, characterization data, NMR spectra, and
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Org. Lett. XXXX, XXX, XXX−XXX