Full Paper
methane. The combined organic layers were washed with brine
and dried over MgSO4. After filtration, the solvent was evaporated
to give the crude material which was dissolved in dichloromethane
and stirred under nitrogen. Acetic formic anhydride (2.5 equiv) was
then added and the resulting solution was stirred overnight at
room temperature, after which, saturated aqueous NaHCO3 was
added and the organic layer was separated. The aqueous layer was
extracted with dichloromethane and the combined organic layers
were dried over MgSO4, filtered and evaporated. The crude mater-
ial was then purified by silica gel column chromatography afford-
ing the desired formamide.
EPSRC mass spectrometry facility at the University of Swansea
for HRMS experiments, and Prof. Phillip Bulman Page (UEA) for
the gift of a sample of the azepine 3c. We thank Professors
Emanuela Licandro and Stefano Maiorana for advice about the
formylation of tetrathiahelicenes using nBuLi and DMF.
Keywords: asymmetric synthesis · chiral formamides · double-
kinetic resolution
resolution
· enantioselective formylation · kinetic
The following formamides 4 f, 4j, 4l, 4q, 4r, 4s, 4t, 4v and 4w
were prepared using Method 3 (for full characterisation data, see
Supporting Information).
[1] Previous reports of stereoselective approaches towards chiral aryl alde-
hydes have relied on an asymmetric lithiation: a) X. Lu, G. Chen, Tetra-
1996, 61, 1172; d) C. Metallinos, J. Zaifman, T. Dudding, L. Van Belle, K.
Synthetic procedures for kinetic resolution using chiral
formamides
Method 4: General procedure for the asymmetric formylation of
7,8-dipropyltetrathia[7]helicene (5), using chiral formamides: In
a 10 mL flame-dried round-bottomed flask filled with argon, to
a solution of 7,8-dipropyltetrathia[7]helicene (5, 70 mg, 0.14 mmol,
1 equiv) in distilled solvent (5 mL) cooled at À788C, was added
dropwise nBuLi (0.14 mmol, 1 equiv). After stirring for 5 min at
À788C, the yellow solution was allowed to reach 08C over 30 min,
and then was cooled again at À788C. Then, a solution of chiral
formamide (0.071 mmol, 0.5 equiv) in distilled solvent (1 mL) was
added dropwise (when using Lewis acid, BF3·Et2O was added drop-
wise to the formamide solution at 08C and stirred for 15 min at
08C before the mixture was added dropwise to the lithiohelicene).
The reaction mixtures were stirred at the temperature and for the
time reported in Tables 1, 2 and 3. Then, saturated aqueous NH4Cl
(1 mL) was added, and the resulting mixture was extracted with
EtOAc (220 mL), dried over MgSO4, filtered and evaporated. The
crude material was then purified by column chromatography (4 g
silica, hexanes/EtOAc gradient 100/0 to 50/1 v/v) affording 7,8-di-
propyl-2-formyltetrathia[7]helicene as a yellow solid (6, yields and
ee values are reported in Tables 1, 2 and 3).
[2] For reviews, see: a) M. Gingras, G. FØlix, R. Peresutti, Chem. Soc. Rev.
[3] For recent advances in asymmetric synthesis of helicenes see: a) M. C.
CarreÇo, A. Enríquez, S. García-Cerrada, M. J. Sanz-Cuesta, A. Urbano, F.
5303; e) M. Weimar, R. Correa da Costa, F.-H. Lee, M. J. Fuchter, Org. Lett.
ˇ
ˇ
ˇ ˇ
2013, 15, 1706; f) J. Zµdny´, A. Jancarík, A. Andronova, M. Sµmal, J. Vacek
ˇ
ˇ
ˇ
Chocholousovµ, J. Vacek, R. Pohl, D. Saman, I. Císarovµ, I. G. Starµ, I.
´
Stary, Angew. Chem. Int. Ed. 2012, 51, 5857; Angew. Chem. 2012, 124,
ˇ ˇ
ˇ
ˇ
5959; g) A. Jancarík, J. Rybµcek, K. Cocq, J. Vacek Chocholousovµ, J.
ˇ
´
Vacek, R. Pohl, L. Bednµrovµ, P. Fiedler, I. Císarovµ, I. G. Starµ, I. Stary,
Angew. Chem. Int. Ed. 2013, 52, 9970; Angew. Chem. 2013, 125, 10154;
h) T. Shibata, T. Uchiyama, Y. Yoshinami, S. Takayasu, K. Tsuchikama, K.
Method 5: General procedure for the asymmetric diformylation
of 7,8-dipropyltetrathia[7]helicene (5), using chiral formamides:
In a 10 mL flame-dried round-bottomed flask filled with argon, to
a solution of 7,8-dipropyltetrathia[7]helicene (5, 70 mg, 0.14 mmol,
1 equiv) in distilled THF (5 mL) cooled at À788C, was added drop-
wise nBuLi (0.29 mmol, 2 equiv). After stirring for 5 min at À788C,
the yellow solution was allowed to reach 08C over 30 min, and
then was cooled again at À788C. Then, a solution of the chiral
formamide (0.14 mmol, 1 equiv) in distilled THF (2 mL) was added
dropwise before stirring at À788C for 18 h. Next, saturated aque-
ous NH4Cl (1 mL) was added, and the resulting mixture was ex-
tracted with EtOAc (220 mL), dried over MgSO4 filtered and
evaporated. The crude material was purified by column chroma-
tography (4 g silica, hexanes/EtOAc gradient 100/0 to 50/1 v/v) af-
fording 7,8-dipropyl-2-formyltetrathia[7]helicene (6, yields and ee
values are reported in Scheme 2) and 2,13-bis(formyl)-7,8-dipropyl-
tetrathia[7]helicene as a yellow solid (7, yields and ee values are re-
ported in Scheme 2).
[4] a) M. Monteforte, S. Cauteruccio, S. Maiorana, T. Benincori, A. Forni, L.
Raimondi, C. Graiff, A. Tiripicchio, G. R. Stephenson, E. Licandro, Eur. J.
Jaimes, D. Dova, F. Rominger, S. Prager, A. Dreuw, E. Licandro, A. S. K.
[5] a) A. Bossi, E. Licandro, S. Maiorana, C. Rigamonti, S. Righetto, G. R. Ste-
[6] E. Licandro, C. Rigamonti, M. T. Ticozzelli, M. Monteforte, C. Baldoli, C.
Giannini, S. Maiorana, Synthesis 2006, 3670.
[7] Improvements to the photochemical preparation of tetrathia[7]heli-
cenes have made this class of helicenes easily available on a multigram
scale, see: a) Ref. [6]. For recent non-photochemical routes to the key
benzo[1,2-b:4,3-b’]dithiophenyl building block, see: b) G. R. Stephenson,
S. Cauteruccio, S. J. Doulcet, Synlett 2014, 25, 701; c) S. Cauteruccio, D.
Dova, C. Graiff, C. Carrara, J. Doulcet, G. R. Stephenson, E. Licandro, New
Acknowledgements
[8] a) E. Jones, I. M. Moodie, Org. Synth. 1988, 6, 979; b) S. Gronowitz,
Chem. Heterocycl. Compd. 1994, 30, 1252.
1998, 9, 2889. For 4c, see: b) P. Ganapati Reddy, G. D. Kishore Kumar, S.
We thank the EPSRC (EH/C009922) and EU Interreg Trans
Manche/Channel cross-border project ‘Academy-Industry
chemistry channel’ (AIcc: ref. 4196) for financial support, the
Chem. Eur. J. 2015, 21, 13431 – 13436
13435
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim