The Use of (−)-Sparteine/Organolithium Reagents for the Enantioselective Lithiation of 7,8-Dipropyltetrathia[7]helicene: Single and Double Kinetic Resolution Procedures

• Published in: Chemistry : a European journal Vol. 21; no. 51; pp. 18677 - 18689
• Main Authors: Doulcet, Julien, Stephenson, G. Richard
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 14.12.2015; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: (−)-sparteine-mediated lithiation; asymmetric synthesis; Asymmetry; Chemistry; Chemistry, Multidisciplinary; Conversion; Crystallography, X-Ray; Diethyl ether; double-KR; Enantiomers; Equivalence; Ethers - chemistry; Indicators and Reagents - chemistry; kinetic resolution; Kinetics; Lithium - chemistry; Molecular Structure; MTBE; Physical Sciences; Polycyclic Compounds - chemistry; Reagents; Science & Technology; Solvents; Sparteine - chemistry; Spirals; Stereoisomerism; Stoichiometry; tetrathiahelicenes; CROSS-CONJUGATED OLIGOTHIOPHENES; ASYMMETRIC-SYNTHESIS; (-)-sparteine-mediated lithiation; OPTICAL-PROPERTIES; HELICENES; MOLECULES; double-KR; TRANSITION METAL-COMPLEXES; HELICAL CHIRALITY; asymmetric synthesis; tetrathiahelicenes; kinetic resolution; 2-PHOTON CIRCULAR-DICHROISM; DERIVATIVES; 2+2+2 CYCLOISOMERIZATION; (−)-sparteine-mediated lithiation
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201502958

The effect of organolithium reagent (RLi: R=nBu, iPr, sBu, tBu), solvent (diethyl ether, diethyl ether/THF and MTBE), and stoichiometry on the (−)‐sparteine‐mediated silylation of 7,8‐dipropyltetrathia[7]helicene shows that, unusually, substantially more than 0.5 equivalent of RLi (R=iPr, sBu, tBu) and a large excess of (−)‐sparteine (R=nBu, sBu) is often needed to achieve substantial conversions and good ee values. With nBuLi, however, just one equivalent of the organolithium reagent is sufficient to obtain high conversions. Our best results were obtained using the convenient tBuLi/(−)‐sparteine adduct with which the need for a high (−)‐sparteine/RLi ratio can be avoided. Single‐ and double‐kinetic resolution (KR) procedures give enantiopure samples of 2‐trimethylsilyl‐ and 2,13‐di(trimethylsilyl)‐7,8‐dipropyltetrathia[7]helicene and two‐step double‐KR combining (−)‐sparteine/sBuLi and chiral formamides affords the synthetically valuable 2‐formyl‐7,8‐dipropyltetrathia[7]helicene. This is the first use of (−)‐sparteine for the enantioselective lithiation of helicenes and the first report of tBuLi outperforming sBuLi in a (−)‐sparteine‐mediated procedure. A show of hands: Sparteine‐mediated asymmetric lithiation distinguishes the two stereochemically identical “left‐” and “right‐hand” ends of the fused spiral of aromatic/heteroaromatic rings in helicenes in double‐kinetic resolution (double‐KR) procedures to provide enantiopure products (see graphic).