Efficient synthesis of cyclopropane-fused heterocycles with bromoethylsulfonium salt

Article abstract of DOI:10.1002/chem.201302081

Lord of the rings! [3.1.0] bicyclic ring systems were synthesized using bromoethylsulfonium triflate and easily available amino acid/aza-Morita-Baylis- Hillman-derived allylic amines. The simple transformation displays a very high degree of diastereoselec

Full text of DOI:10.1002/chem.201302081

COMMUNICATION
DOI: 10.1002/chem.201302081
Efficient Synthesis of Cyclopropane-Fused Heterocycles with
Bromoethylsulfonium Salt
Sven P. Fritz,[a] Johnathan V. Matlock,[a] Eoghan M. McGarrigle,*[b] and
Varinder K. Aggarwal*[a]
The 3-azabicycloACHTUNGTRENNUNG[3.1.0]hexane is a common motif in natu-
ral products.[1–6] Furthermore this rigid framework repre-
sents a privileged class of pharmacologically active com-
pounds, often showing enhanced binding affinities with their
targets (Figure 1).[7] These bicycles also represent conforma-
tionally restricted analogues of piperidines (e.g. trovafloxa-
cin).[8] When substituted with a carboxylic acid moiety, they
resemble conformationally restricted analogues of gluta-
mate, gamma-amino butyric acid (GABA) or a/b-proline
analogues (Figure 2).[9]
Numerous methods have been developed for the con-
struction of azabicycloACHTNUTGRNEUNG
[3.1.0]hexanes.[10] These include the
Kulinkovich/de Meijere reaction,[11,12] cyclisation of tethered
amines with metals (Pd,[13] Ru,[14] Rh,[15] Ag[16]), cyclisation
of tethered cyclopropanes[17] and the Simmons–Smith[18]
/
Corey–Chaykovsky[19]/sulfur ylide–Au[20] cyclopropanations.
These methods are usually only effective in the synthesis of
one specific type of scaffold.
We were keen to develop a general strategy that could de-
liver 3-azabicycloACHTUNGTRENNUNG[3.1.0]hexanes with a range of functional
groups in a range of positions. Our design plan for the syn-
thesis of the scaffold was to effect a tandem process initiated
by conjugate addition of an unsaturated amine 1 to vinyl
sulfonium salt 2, generated in situ from the stable and crys-
talline salt 3 (Scheme 1). The intermediate sulfur ylide 4
would undergo intramolecular addition to the Michael ac-
ceptor to give a sulfonium enolate 5, which would ring-close
to the cyclopropane 6.
Figure 1. Selected examples of important bicycloACTHUNRTGNEUNG[3.1.0]hexanes.
This tandem process is related to the previously described
reactions that bear aldehydes or imines in place of Michael
[a] Dr. S. P. Fritz, J. V. Matlock, Prof. Dr. V. K. Aggarwal
School of Chemistry, University of Bristol
Cantockꢀs Close, Bristol, BS8 1TS (UK)
Fax : (+44)117-925-1295
Figure 2. Conformationally restricted scaffolds discussed in this work.
E-mail: v.aggarwal@bristol.ac.uk
Homepage: http://www.bris.ac.uk/chemistry/research/organic/aggar-
wal-group/
[b] Dr. E. M. McGarrigle
Centre for Synthesis and Chemical Biology
UCD School of Chemistry and Chemical Biology
University College Dublin, Belfield, Dublin 4 (Ireland)
E-mail: eoghan.mcgarrigle@ucd.ie
Homepage: http://mcgarrigleresearch.wordpress.com/
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201302081.
Scheme 1. Proposed mechanism of the reaction. B=base; EWG=elec-
tron-withdrawing group.
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Table 1. Scope of the transformation.[a]
acceptors, giving fused bicyclic epoxides and aziridines, re-
spectively.[21,22] However, the more complex reaction with
Michael acceptors (leading to products with additional ster-
eogenic centres) has not been previously reported.[23] The
potential for a very rapid increase in molecular complexity
from simple starting materials was an additional attractive
feature of the chemistry. In this paper, we report the suc-
cessful realisation of this strategy and the formation of
azabicycloACHTUNGTRENNUNG[3.1.0]hexanes with surprisingly high diastereose-
lectivity.
Our studies began with the preparation of a diverse array
of allylic amines. The allylic amines 1a–g were prepared in
one step by using either cross-metathesis[24] or Wittig chem-
istry. Similarly, 1h–j were synthesized in two steps from
commercially available, amino-acid derived methyl esters
through a diisobutylaluminium hydride (DIBAL-H) reduc-
tion/Wittig reaction sequence. Allylic amines 1k, and 1l
with the appropriate protecting groups required several
steps,[25] whilst 1m was available in one step from reaction
of dihydrocinnamaldehyde with a vinylchromium nucleo-
phile (see Supporting Information for details).[26]
The reaction of unsaturated amide 1a with the stable and
crystalline salt 3 was initially tested. After optimisation of
the process (see Supporting Information for details), a set of
conditions were established (method A) that led to moder-
ate–high yields of the [3.1.0] bicycles with complete diaster-
eoselectivity (Table 1).[27] For example, unsaturated amide
1a gave the cyclopropane 6a in 62% yield as a single dia-
stereomer. The Michael acceptors tested bore a range of
electron-withdrawing groups, including Me and tBu esters,
ketones, amides and nitriles (6a–e). Furthermore, in the
case of the unsubstituted allylic amide, the N-Cbz (Cbz=
carbobenzyloxy) carbamate 1 f[28] could also be employed in
place of the tosyl protecting group leading to the pyrrolidine
6 f. The piperidine 6g was also accessible using the same
process and again was formed with complete diastereoselec-
tivity.
[a] All yields are isolated yields and diastereomeric ratio (d.r.) is deter-
mined by 1H NMR spectroscopy of the crude material. [b] Yield of TBS
deprotected product including an in situ deprotection with TBAF
(5 equiv) added after 15 h. [c] Reaction at 08C, if run at RT yield is 75%
and d.r. is 7:1. [d] Minor traces of the other diastereoisomer are visible in
the 1H NMR spectrum. SES=2-(trimethylsilyl)ethanesulfonyl, TBAF=
tetrabutylammonium fluoride.
The method was further extended to a range of a-substi-
tuted allylic amines (1h–m), although in this case NaH was
found to be superior to 1,8-diazabicyclo
(DBU; method B, Table 1). With a small substituent (Me,
1h), the azabicyclo[3.1.0] hexane 6h was formed with low
ACHTUNGTREN[NUNG 5.4.0]undec-7-ene
ACHTUNGTRENNUNG
diastereoselectivity but with larger substituents (1i, 1j) the
adducts (6i, 6j) were formed with essentially complete dia-
stereoselectivity. In terms of the N-protecting group, with a-
substituted allylic amines, it was not possible to use the Cbz
or tert-butoxycarbonyl (Boc) groups, but the more easily
cleavable[28] 1-naphthyl or 2-(trimethylsilyl)ethyl sulfona-
mides (1k, 1l) worked well giving similarly high yields and
diastereoselectivities. Interestingly, allylic alcohol 1m could
also be used and gave the tetrahydrofuran 6m, again with
high selectivity. The methodology readily lent itself to the
preparation of enantioenriched products, as illustrated with
6k and 6l, since the a-substituted allylic amines are easily
obtained from chiral amino acids (serine in this case).
7a–c[29] (one step from the acrylate), as the starting materi-
als for the cyclisation. These reactions now led to the forma-
tion of b-proline-derived fused cyclopropanes 8a–c
(Table 2).[30]
Whilst unsaturated esters 7a and 7b worked well, giving
the corresponding adducts 8a and 8b, respectively, in high
yields with very high diastereoselectivity, unsaturated
ketone (7c) behaved differently. In this case the major prod-
uct was the epoxy-annulation adduct 9. Evidently, after 1,4-
addition of the amide 7c to the vinyl sulfonium salt 1, the
ylide intermediate reacts in a more favoured 6-exo-trig
mode with the ketone moiety, rather than the desired 6-
endo-trig mode with the alkene. Nevertheless, the pyrroli-
dine 8c was formed with high diastereoselectivity as before.
The methodology readily lends itself to asymmetric synthe-
Expanding this methodology further, we were able to uti-
lise easily accessible aza-Morita–Baylis–Hillman adducts
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Efficient Synthesis of Cyclopropane-Fused Heterocycles
Table 2. Reactivity of (aza)-Morita-Baylis–Hillman adducts.[a]
COMMUNICATION
7a: X=OMe
7b: X=OtBu
7a: X=OMe (82% ee)
(Æ)-8a, 64%, >20:1 d.r.
(Æ)-8b, 45%, >20:1 d.r.
Scheme 3. Formation of 11 with b-CF3 vinylsulfonium salt 10.
(+)-8a, 63%, >20:1 d.r; 82% ee
(>99% ee after recrystallization)[b]
11,[33] again with essentially complete diastereoselectivity[21i]
(Scheme 3).
The synthetic utility of the methodology is illustrated
through a range of functional-group transformations of sev-
eral of the [3.1.0]pyrrolidines. For example, oxidative cleav-
age of the Ph group[34] in 8a gave pyrrolidine 12 , which is
both an a- and a b-amino acid derivative (Scheme 4).[35] De-
7c: X=Me
[a] All yields are isolated yields and d.r. is determined by 1H NMR spec-
troscopy of the crude. [b] The ee was determined by chiral supercritical-
fluid chromatography (SFC), see the Supporting Information for full de-
tails.
sis, since the aza-Morita–Baylis–Hillman adducts 7a,b are
obtainable using asymmetric organocatalysis.[31] This was il-
lustrated by the use of (+)-7a (82% ee; ee=enantiomeric
excess), which gave the [3.1.0] bicycle (+)-8a without meas-
urable racemization, which was increased to >99% ee after
recrystallization.
Scheme 4. Oxidation to a,b-amino acid derivative 12.
The relative stereochemistry of cyclopropanes 6g, 6i, and
8a were determined by X-ray analysis and related com-
pounds were assigned by analogy (see the Supporting Infor-
mation for details). It is believed that the steps prior to ring
closure are reversible and that the selectivity is determined
in the nonreversible ring-closure step that forms the cyclo-
propane. The origin of selectivity of the two classes of sub-
strates 1 and 7 can be rationalised by considering the non-
bonded steric interactions in the TSs for which the less hin-
dered X1 and Y1 are favoured over X2 and Y2, which sub-
sequently leads to the preferred formation of trans (6h–m)
and cis (8a–c) isomers (Scheme 2).
Scheme 5. Deprotection and transformation of 6l: a) CsF (5 equiv), DMF
(0.1m), 958C, 4 h then b) Boc2O (1.2 equiv), NEt3 (3 equiv), CH2Cl2, RT,
2 h, 62% over 2 steps; c) PDC (4 equiv), DMF (0.5m), ref. [36], 63%.
PDC=pyridinium dichromate.
protection and oxidation of 6l gave the conformationally
The cyclopropanation–annulation reaction was further ex-
tended to include the medicinally important CF3 group.
Thus, reaction of 1a with the CF3-substituted vinyl sulfoni-
um salt 10[32] gave the CF3-substitued [3.1.0]pyrrolidine
locked glutamic acid analogue 14
Finally, pyrrolidine 6 f was converted into 6-amino-3-
(Scheme 5).[36]
ACHTUNGTRENNUNG
azabicycloACTHNUTRGNEUG[N 3.1.0]hexan-3-ium chloride 16, an intermediate
used in the synthesis of trovafloxacin, a potent antibiotic.[4]
Thus, saponification of the ester 6 f, followed by the Schmidt
reaction with diphenyl phosphoryl azide (DPPA) gave pyr-
Scheme 6. Formal synthesis of the trovafloxacin precursor 16: a) aq.
NaOH (1m), THF, RT, 15 h then b) DPPA (1.1 equiv), NEt3 (1.1 equiv),
BnOH (5 equiv), PhMe (0.25m), 908C, 1.5 h, 62% (0.3 g scale) over
2 steps; c) H2 (1 atm), Pd/C (cat.), HCl in Et2O (2m, 3 equiv), MeOH,
RT, 3 h, 99%.
Scheme 2. Model for diastereoselectivity in the formation of 6 and 8.
Chem. Eur. J. 2013, 19, 10827 – 10831
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10829

Dr. E. McGarrigle, Prof. Dr. V. Aggarwal et al.
T. J. Musick, F. P. Duncanson, W. E. Bridson, Drug Metab. Dispos.
2008, 36, 252–259.
[6] D. D. Schoepp, B. G. Johnson, R. A. Wright, C. R. Salhoff, N. G.
Mayne, S. Wu, S. L. Cockerham, J. P. Burnett, R. Belegaje, D. Bleak-
man, J. A. Monn, Neuropharmacology 1997, 36, 1–11.
[7] For an example, see S. J. Miller, R. H. Grubbs, J. Am. Chem. Soc.
1995, 117, 5855–5856.
[8] a) J. A. Sattigeri, M. M. S. Andappan, K. Kishore, S. Thangathirupa-
thy, S. Sundaram, S. Singh, S. Sharma, J. A. Davis, A. Chugh, V. S.
Bansal, Bioorg. Med. Chem. Lett. 2008, 18, 4087–4091.
rolidine 15. Finally, hydrogenolysis gave amino pyrrolidine
16 in just a few synthetic steps (Scheme 6).
In conclusion we have developed a novel, efficient and
versatile route for the formation of cyclopropane-fused het-
erocycles from easily available starting materials. In compar-
ison to previous methods, this protocol enables the synthesis
of a more diverse range of substituted and functionalized
[3.1.0] scaffolds with very high diastereoselectivity. There is
considerable interest in exploring this class of bioactive
compounds, which should now be enabled by the methodol-
ogy described herein.
[9] a) B. Meldrum, Nature 1995, 376, 122–123; b) R. Galeazzi, G. Mob-
bili, M. Orena, Tetrahedron: Asymmetry 1997, 8, 133–137.
[10] G. R. Krow, K. C. Cannon, Org. Prep. Proced. Int. 2000, 32, 103–
122.
[11] O. G. Kulinkovich, S. V. Sviridov, D. A. Vasilevskii, T. S. Pritytskaya,
Zh. Org. Khim. 1989, 25, 2244–2245.
[12] a) V. Chaplinski, A. deMeijere, Angew. Chem. 1996, 108, 491–492;
Angew. Chem. Int. Ed. Engl. 1996, 35, 413–414; b) M. Gensini, S. I.
Kozhushkov, D. S. Yufit, J. A. K. Howard, M. Es-Sayed, A. de Mei-
jere, Eur. J. Org. Chem. 2002, 2499–2507.
[13] a) H. Ohno, Y. Takeoka, K. Miyamura, Y. Kadoh, T. Tanaka, Org.
Lett. 2003, 5, 4763–4766; b) B. de Carne-Carnavalet, A. Archam-
beau, C. Meyer, J. Cossy, B. Folleas, J. L. Brayer, J. P. Demoute,
Chem. Eur. J. 2012, 18, 16716–16727.
[14] M. Eckert, S. Moulin, F. Monnier, I. D. Titanyuk, S. N. Osipov, T.
Roisnel, S. Derien, P. H. Dixneuf, Chem. Eur. J. 2011, 17, 9456–
9462.
Experimental Section
General: A stirred solution of amine or alcohol 1 (1.0 equiv) and diphen-
yl bromoethyl sulfonium salt 3 (1.25 equiv, commercially available) in an-
hydrous solvent (0.1m) at room temperature under an inert atmosphere
was treated with base (3.5 equiv) and stirred for the indicated time (until
complete consumption of starting material was detected by HPLC or
TLC analysis). The reaction mixture was then quenched with 10% aque-
ous citric acid solution (15 mL per mmol of 1) and the aqueous layer was
extracted with CH2Cl2 (3ꢂ30 mLper mmol of 1) . The combined organic
layers were washed with brine (30 mL per mmol of 1), dried (MgSO4)
and concentrated in vacuo. The crude reaction mixture was purified by
flash chromatography, eluting with either EtOAc/n-pentane or Et2O/n-
pentane to give the desired product.
[15] J. J. Feng, J. L. Zhang, J. Am. Chem. Soc. 2011, 133, 7304–7307.
[16] A. Kamimura, A. Kadowaki, T. Yoshida, R. Takeuchi, H. Uno,
Chem. Eur. J. 2009, 15, 10330–10334.
[17] V. V. Tverezovsky, M. S. Baird, I. G. Bolesov, Tetrahedron 1997, 53,
14773–14792.
[18] A. R. Renslo, P. Jaishankar, R. Venkatachalam, C. Hackbarth, S.
Lopez, D. V. Patel, M. F. Gordeev, J. Med. Chem. 2005, 48, 5009–
5024.
[19] F. M. Sabbatini, S. Melotto, G. Bernasconi, S. M. Bromidge, L.
D’Adamo, M. Rinaldi, C. Savoia, C. Mundi, C. Di Francesco, L.
Zonzini, V. J. A. Costantini, B. Perini, E. Valerio, A. Pozzan, E. Per-
dona, F. Visentini, M. Corsi, R. Di Fabio, ChemMedChem 2011, 6,
1981–1985.
Acknowledgements
S.P.F. thanks the EPSRC (Engineering and Physical Sciences Research
Council) for a studentship. J.V.M. thanks the EPSRC, GSK (Glaxo-
SmithKline) and BCS CDT (Bristol Chemical Synthesis Centre for Doc-
toral Training) for a studentship. V.K.A. thanks the EPSRC for a Senior
Research Fellowship. E.M.M. thanks the Science Foundation Ireland and
Marie-Curie COFUND for a SIRG award (Grant Number 11/SIRG/
B2154). We thank Dr. C. Butts (University of Bristol) and Dr. M.
Haddow (University of Bristol) for NMR spectra and X-ray assistance,
respectively.
[20] X. Huang, S. Klimczyk, L. F. Veiros, N. Maulide, Chem. Sci. 2013, 4,
1105–1110.
[21] For epoxide and aziridine-fused heterocycles, see: a) K. H. Kim,
L. S. Jimenez, Tetrahedron: Asymmetry 2001, 12, 999–1005 and ref-
erences therein; b) H. Yamanaka, J. Matsuo, A. Kawana, T. Mu-
kaiyama, ARKIVOC 2004, 3, 42–65 and references therein; c) M. G.
Unthank, N. Hussain, V. K. Aggarwal, Angew. Chem. 2006, 118,
7224–7227; Angew. Chem. Int. Ed. 2006, 45, 7066–7069; d) C. G.
Kokotos, E. M. McGarrigle, V. K. Aggarwal, Synlett 2008, 2191–
2195; e) M. G. Unthank, B. Tavassoli, V. K. Aggarwal, Org. Lett.
2008, 10, 1501–1504; f) S. Catalan-Munoz, C. A. Muller, S. V. Ley,
Eur. J. Org. Chem. 2010, 183–190; g) E. M. McGarrigle, M. Yar,
M. G. Unthank, V. K. Aggarwal, Chem. Asian J. 2011, 6, 372–375;
h) S. P. Fritz, Z. Ali, M. G. Unthank, E. M. McGarrigle, V. K. Aggar-
wal, Helv. Chim. Acta 2012, 95, 2384–2398; i) S. P. Fritz, T. H. West,
E. M. McGarrigle, V. K. Aggarwal, Org. Lett. 2012, 14, 6370–6373.
[22] For all other heterocycles, see: a) M. Yar, E. M. McGarrigle, V. K.
Aggarwal, Angew. Chem. 2008, 120, 3844–3846; Angew. Chem. Int.
Ed. 2008, 47, 3784–3786; b) M. Hansch, O. Illa, E. M. McGarrigle,
V. K. Aggarwal, Chem. Asian J. 2008, 3, 1657–1663; c) M. Yar,
E. M. McGarrigle, V. K. Aggarwal, Org. Lett. 2009, 11, 257–260;
d) C. S. Xie, D. Y. Han, J. H. Liu, T. Xie, Synlett 2009, 3155–3158;
e) J. Bornholdt, J. Felding, J. L. Kristensen, J. Org. Chem. 2010, 75,
7454–7457; f) C. S. Xie, D. Y. Han, Y. Hu, J. H. Liu, T. A. Xie, Tetra-
hedron Lett. 2010, 51, 5238–5241; g) V. K. Aggarwal, S. P. Fritz, A.
Mumtaz, M. Yar, E. M. McGarrigle, Eur. J. Org. Chem. 2011, 3156–
3164; h) E. M. McGarrigle, S. P. Fritz, L. Favereau, M. Yar, V. K.
Aggarwal, Org. Lett. 2011, 13, 3060–3063; i) S. P. Fritz, J. F. Moya,
M. G. Unthank, E. M. McGarrigle, V. K. Aggarwal, Synthesis 2012,
Keywords: amino acids
·
Baylis–Hillman reaction
·
cyclopropanes · heterocycles · sulfur ylides
[1] a) I. Takahashi, K. Takahashi, M. Ichimura, M. Morimoto, K.
Asano, I. Kawamoto, F. Tomita, H. Nakano, J. Antibiot. 1988, 41,
1915–1917; b) D. L. Boger, D. S. Johnson, Proc. Natl. Acad. Sci.
USA 1995, 92, 3642–3649; c) T. Wirth, K. Schmuck, L. F. Tietze,
S. A. Sieber, Angew. Chem. 2012, 124, 2928–2931; Angew. Chem.
Int. Ed. 2012, 51, 2874–2877.
[2] a) S. Gomi, D. Ikeda, H. Nakamura, H. Naganawa, F. Yamashita, K.
Hotta, S. Kondo, Y. Okami, H. Umezawa, Y. Iitaka, J. Antibiot.
1984, 37, 1491–1494; b) G. Kim, M. Y. Chumoyer, S. J. Danishefsky,
G. K. Schulte, J. Am. Chem. Soc. 1993, 115, 30–39.
[3] F. G. Njoroge, K. X. Chen, N. Y. Shih, J. J. Piwinski, Acc. Chem. Res.
2008, 41, 50–59.
[4] T. Norris, T. F. Braish, M. Butters, K. M. DeVries, J. M. Hawkins,
S. S. Massett, P. R. Rose, D. Santafianos, C. Sklavounos, J. Chem.
Soc. Perkin Trans. 1 2000, 1615–1622.
[5] a) F. Xu, J. A. Murry, B. Simmons, E. Corley, K. Fitch, S. Karady, D.
Tschaen, Org. Lett. 2006, 8, 3885–3888; b) P. A. Krieter, M. Gohdes,
10830
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Efficient Synthesis of Cyclopropane-Fused Heterocycles
COMMUNICATION
44, 1584–1590; j) M. Yar, S. P. Fritz, P. J. Gates, E. M. McGarrigle,
V. K. Aggarwal, Eur. J. Org. Chem. 2012, 160–166.
[30] For examples of ring contractions from 6-membered rings to 5,3-
fused bicycles, see a) N. A. Nelson, G. Mortimer, J. Org. Chem.
1957, 22, 1146–1151; b) K. B. Wiberg, D. R. Artis, G. Bonneville, J.
Am. Chem. Soc. 1991, 113, 7969–7979; c) S. M. Jeffery, S. Niedoba,
C. J. M. Stirling, J. Chem. Soc. Chem. Commun. 1992, 650–652.
[31] For a review, see a) Y. Wei, M. Shi, Chem. Rev. 2013, 10.1021/
cr300192h; b) Y. Iwabuchi, M. Nakatani, N. Yokoyama, S. Hatakeya-
ma, J. Am. Chem. Soc. 1999, 121, 10219; c) M. Shi, Y.-M. Xu, Y.-L.
Shi, Chem. Eur. J. 2005, 11, 1794–1802.
[32] a) R. Maeda, K. Ooyama, R. Anno, M. Shiosaki, T. Azema, T Hana-
moto, Org. Lett. 2010, 12, 2548–2550; b) H. Lin, Q. L. Shen, L. Lu,
J. Org. Chem. 2011, 76, 7359–7369; c) N. Kasai, R. Maeda, H.
Furuno, T. Hanamoto, Synthesis 2012, 44, 3489–3495.
[33] O. S. Artamonov, E. Y. Slobodyanyuk, O. V. Shishkin, I. V. Komarov,
P. K. Mykhailiuk, Synthesis 2013, 45, 225–230.
[23] For the synthesis of non-fused cyclopropanes with a vinylsulfonium
salt, see: a) J. Gosselck, G. Schmidt, Tetrahedron Lett. 1969, 10,
2615–2618; b) J. Gosselck, G. Schmidt, Angew. Chem. 1968, 80,
439–440; Angew. Chem. Int. Ed. Engl. 1968, 7, 456–458; c) Z. J.
Mao, H. J. Qu, Y. Y. Zhao, X. F. Lin, Chem. Commun. 2012, 48,
9927–9929.
[24] a) T. J. Donohoe, J. F. Bower, J. A. Basutto, Nat. Protoc. 2010, 5,
2005–2010; b) A. W. Van Zijl, A. J. Minnaard, B. L. Feringa, J. Org.
Chem. 2008, 73, 5651–5653.
[25] S. Hanessian, S. Ninkovic, U. Reinhold, Tetrahedron Lett. 1996, 37,
8971–8974.
[26] K. Namba, Y. Kishi, Org. Lett. 2004, 6, 5031–5033.
[27] During optimisation both a mild (DBU) and a strong (NaH) base
were used for the synthesis of 6a, giving a single diastereomer in
both cases. Thus it is unlikely that the diastereoselectivity arises by
epimerisation at the centre a to the electron-withdrawing group.
[28] T. W. Greene, P. G. M. Wuts, Protective Groups in Organic Synthesis,
3rd ed., Wiley, Hoboken, 1999.
[34] M. T. Nunez, V. S. Martin, J. Org. Chem. 1990, 55, 1928–1932.
[35] N. A. Sasaki, R. Pauly, C. Fontaine, A. Chiaroni, C. Riche, P. Potier,
Tetrahedron Lett. 1994, 35, 241–244.
[36] R. Zhang, A. Mamai, J. S. Madalengoitia, J. Org. Chem. 1999, 64,
547–555.
[29] D. Basavaiah, A. J. Rao, T. Satyanarayana, Chem. Rev. 2003, 103,
811–891.
Received: May 31, 2013
Published online: July 10, 2013
Chem. Eur. J. 2013, 19, 10827 – 10831
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
10831