Ambient-Pressure Asymmetric Preparation of S,S-DICHED, a C ₂-Symmetrical Director for Matteson Reactions

◊ These authors contributed equally to this work.

Abstract

A synthesis of S,S-DICHED (dicyclohexylethane-1,2-diol), a C ₂-symmetrical chiral director for Matteson homologations, is described. It relies on the insertion of lithiated S-2-cyclohexyloxirane into cyclohexylboronic acid pinacol ester and proceeds in three linear steps from readily available starting materials. No step requires chromatography or any specialized equipment.

Key words

DICHED - DIPED - Matteson reaction - lithiated epoxide - ­chiral director

• References and Notes


Recent reviews:
• 1a Matteson DS. J. Org. Chem. 2013; 78: 10009
• 1b Thomas SP. French RM. Jheengut V. Aggarwal VK. Chem. Rec. 2009; 9: 24

Original articles:
• 1c Matteson DS. Majumdar D. J. Am. Chem. Soc. 1980; 102: 7588
• 1d Matteson DS. Ray R. J. Am. Chem. Soc. 1980; 102: 7590
• 1e Tripathy PB. Matteson DS. Synthesis 1990; 200
• 2a Hoffmann RW. Ditrich K. Köster G. Stürmer R. Chem. Ber. 1989; 122: 1783
• 2b Sharpless KB. Amberg W. Bennani YL. Crispino GA. Hartung J. Jeong KS. Kwong HL. Morikawa K. Wang ZM. J. Org. Chem. 1992; 57: 2768
• 3 Hiscox WC. Matteson DS. J. Org. Chem. 1996; 61: 8315
• 4 Ref. 3 reports problems with overreduction when using the procedure described in ref. 2. Our attempts to run the procedure in ref. 3 on 0.5–2 g scales required some dilution, leading to mixtures of starting material and (partially) hydrogenated product. Ref. (3) also describes RhCl₃ recovery.
• 5a Vedrenne E. Wallner OA. Vitale M. Schmidt F. Aggarwal VK. Org. Lett. 2009; 11: 165

Also see:
• 5b Alwedi E. Zakharov LN. Blakemore PR. Eur. J. Org. Chem. 2014; 6643
• 6 Huang K. Wang H. Stepanenko V. De Jesús M. Torruellas C. Correa W. Ortiz-Marciales M. J. Org. Chem. 2011; 76: 1883
• 7 We initially thought that the 1,2-rearrangement/epoxide opening had to be facilitated by a Lewis acid, the role of which could be fulfilled by excess boronate. However, attempts to replace it with ZnCl₂ or TMSCl (added after LiTMP) resulted in lower conversions of 5 and thus lower yields. The formation of an ate complex of type 10 after the 1,2-rearrangement would explain this observation if the rearrangement occurs as fast/faster than the formation of 9.
• 8 Singh RP. Matteson DS. J. Org. Chem. 2000; 65: 6650
• 9 Struth FR. Hirschhäuser C. Eur. J. Org. Chem. 2016; 958
• 10 Based on our previous studies (ref. 9) we expected a de of 80% for the homologation of 11 with LiCHX₂ under the employed conditions. However, we did expect the de to increase again after substitution with vinyl Grignard (→ 12) due to the double stereodifferentiation discovered by Matteson for this type of chiral director (ref. 1e). See Supporting Information for further discussion.
• 11 Matteson DS. Beedle EC. Kandil AA. J. Org. Chem. 1987; 52: 5034
• 12 Procedure for the Preparation of SS -1 Immediately before the reaction, LiTMP was prepared in a separate flask by addition of n-BuLi (2 equiv, 1.6 M in hexanes) to a solution of dry tetramethylpiperidine (2 equiv) in dry THF (1 L/mol of LiTMP) at 0 °C. The LiTMP solution was stirred for 0.5 h at r.t., transferred into a dropping funnel and added dropwise to a solution of epoxide 5 (1 equiv) and boronate 6 (2 equiv) in THF (1 L/mol of 6) with cooling in an ice bath (0 °C). Afterwards the reaction mixture was stirred for 0.5 h at 0 °C and 1.5 h at 13–14 °C (p-xylene/dry ice bath). The reaction mixture was cooled to 0 °C before aq. NaOH (2 M, 3.5 equiv) and aq. H₂O₂ (30%, 10 equiv) were added simultaneously. After stirring for 30 min aq. Na₂S₂O₅ (2 M) was added over the course of 15 min at the same temperature. Stirring was continued for 5 min before Et₂O and H₂O were added and the phases were separated. The aqueous layer was re-extracted with Et₂O, and the combined organic layers were washed with sat. aq. NH₄Cl, brine and aq. NaOH (1 M). The organic phase was dried over MgSO₄, filtered, and the solvent was removed in vacuo to yield a yellow solid. Recrystallization from EtOH or chromatography on silica (CyHex/EtOAc, 9:1) yielded SS-1 in 55–60% yield. R_f = 0.28 (CyHex/EtOAc, 4:1). ¹H NMR (300 MHz, CDCl₃): δ = 3.45–3.25 (m, 2 H), 1.95–1.42 (m, 12 H), 1.34–0.95 (m, 10 H). ¹³C NMR (75 MHz, CDCl₃): δ = 75.1, 40.4, 29.6, 28.2, 26.4, 26.2, 26.1. ¹H NMR and ¹³C NMR data were consistent with those previously reported by: Scott MS. Lucas AC. Luckhurst CA. Prodger JC. Dixon DJ. Org. Biomol. Chem. 2006; 4: 1313