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New 1,2-diamine-based and 2-aminothioether-based chiral ligands were prepared. The carbon skeleton had as a common feature a six member ring. The starting materials used were trans-1,2-diaminocyclohexane, cyclohexaneazidirine and 11,12-diamino-9,10-dihydro-9,10-ethanoanthracene. Also chiral compounds such as (S)-alpha-phenylethylamine, (S)- and (R)-camphorsulfonyl chloride were used in the preparation of the ligands.

Different functionalities were introduced i.e. thiourea, sulfonamide, bis(sulfonamide)diol and Schiff bases.

Most of the new compounds were evaluated in catalytic asymmetric C-H and C-C bond formation reactions in the presence of zinc. Mainly the asymmetric hydrosilylation, alkylation of prochiral ketones have been performed.

1.   Catalytic asymmetric hydrosilylation of acetophenone with new chiral thiourea ligands containing the (S)-a-phenylethyl group.

New chiral thioureas A containing trans-1,2-diaminocyclohexane, derived from cyclohexane oxide with (S)-alpha-phenylethylamine have been prepared (79–98% yield). Thioureas A were used as ligands for the zinc-based catalyzed asymmetric hydrosilylation of acetophenone with polymethylhydrosiloxane (PMHS). The best result was achieved with monothiourea 1 (up to 75% ee), in toluene and a catalyst load of 5 mol %. This work was published in Tetrahedron: Asymmetry 20 (2009) 2788–2794

2.   Catalytic asymmetric hydrosilylation of acetophenone with new Schiff bases B from trans-2-(alkyl and arylthio)cyclohexanoamines.

Anabel B. González-Guillén undergraduate research project was the preparation of trans-2-(phenyl thio)cyclohexane amine from cyclohexane aziridine and thiophenol. Resolution with (S)-mandelic acid afford the (R,S,S)-2-aminothioether in 45% yield. Then the reaction with benzaldehyde, salicilaldehyde,  and 2,4-tert-butylsaliciladehyde afforded the Schiff bases in high yields (91 – 93%). 

Haydee Rojas Cabrera a postdoctoral student worked on the preparation of 2-aminothioethers from less nucleophilic thiols. The ring opening was accomplished from N-Boc-cyclohexane aziridine in the presence of a Lewis acid.³ The used of BF₃ etherate as Lewis acid in the reaction with t-butylthiol and cyclohexanethiol  afforded the products in high yields (95%). The resolution of aminothioethers with (S)-mandelic acid, followed by the nucleophilic addition of aldehydes to the chiral (R,S,S)-2-aminothioethers afforded the corresponding Schiff bases.

Low yields and enantioselectivities were achieved in the catalytic asymmetric hydrosilylation of acetophenone with the new Schiff bases.

3.   Catalytic asymmetric hydrosilylation of acetophenone with 11,12-Diamino-9,10-dihydro-9,10-ethanoanthracene Diamine–based Thioureas C.

Tania Sanchez Bulás is a bachelor student, who worked in the preparation of thioureas C, as her undergraduate research project. The ligand syntheses began from resolved 11,12-diamino-9,10-dihydro-9,10-ethanoanthracene diamine.¹  She prepared the monothioureas (54 – 73% yield) and dithioureas 13- 16 (87 – 91%  yield).  The thioureas C were used as zinc-catalysts in the hydrosilylation reaction of acetophenone with low yields and enantioselectivities.

4.   11,12-Diamino-9,10-dihydro-9,10-ethanoanthracene Diamine–based Monosulfonamides Ligands for the Asymmetric Addition of Diethylzinc to benzaldehyde.

Gabriela Huelgas, a postdoctoral student, worked on the preparation of monosulfonamides D. The ligand syntheses began from resolved 11,12-diamino-9,10-dihydro-9,10-ethanoanthracene diamine¹ affording monosulfonamides D (64 - 95    % yield). First, the hydrosilylation reaction of acetophenone with low yields and enantioselectivities was performed. Then, the asymmetric addition of diethylzinc to benzaldehyde afforded up to 47% ee and 92% yield. The manuscript of this work is in preparation. We are planning to submit it to Tetrahedron: Asymmetry.

5.   C₂-Symmetric 11,12-diamino-9,10-dihydro-9,10-ethanoanthracene Diamine–based Catalyst for the Asymmetric Addition of Alkylzinc Reagents to Ketones.

The ligand syntheses began from resolved 11,12-diamino-9,10-dihydro-9,10-ethanoanthracene diamine¹ and either (S)- or(R)-camphor sulfonyl chloride. Reaction of the resolved diamines with 2 equiv. of (S)-camphor sulfonyl chloride, in the presence of 2 equiv. triethylamine resulted in formation of the corresponding diones in 72–78% isolated yield after purification on silica gel.

Reduction of the dione ligands was accomplished with excess sodium borohydride in THF/ethanol to provide diols in 68–70% yield as a 4:1 mixture of diastereomeric endo-endo:exo-endo.

Endo-endo diastereomeric ligands were employed at 2 and 5 mol % with acetophenone reaching up to 99% enantioselectivity at 5 mol % catalyst loading. The manuscript of this work is in preparation. We are planning to submit it to Advanced Synthesis and Catalysis.

 References.
1.    Fox, M. E.; Gerlach, A.; Lennon, I. C.; Meek, G.; Praquin, C. Synthesis 2005, 19, 3196.
2.    Gayet, A.; Bolea, C. Andersson, P. G.  Org. Biomol. Chem. 2004, 2, 1887-1893.

3. Ekegreen, J. K.; Roth, P.; Kallstrom, K.; Tarnai, T.; Andersson, P. Org. Biomol. Chem., 2003, 1, 358.