Enantiopure Guanidine Bases For Enantioselective Enone Epoxidations: 1, Acyclic Guanidines

Abstract

A range of structurally and functionally varied enantiopure guanidines has been prepared and evaluated in the enantioselective epoxidation of 3-tert-butoxycarbonylamino-4,4-dimethoxycyclohexa-2,5-dien-1-one 1 using tert-butylhydroperoxide. Successful enantioselective epoxidations were observed and useful structure-activity data obtained, but the reactions were slow and the maximum ee observed was 30%.

enantioselective - epoxidation - enones - guanidines - stereoselectivity

References

For reviews on epoxy ketones as versatile building blocks see:

1a Lauret C. Tetrahedron: Asymmetry  2001,  12:  2359 

1b Bonini C. Righi G. Tetrahedron  2002,  58:  4981 

2 For a review see: Porter MJ. Skidmore J. Chem. Commun.  2000,  1215 

3a Gautier ECL. Lewis NJ. McKillop A. Taylor RJK. Tetrahedron Lett.  1994,  35:  8759 

3b McKillop A. McLaren L. Taylor RJK. Watson RJ. Lewis N. J. Chem. Soc., Perkin Trans. 1  1996,  1385 

3c Graham AE. McKerrecher D. Davies DH. Taylor RJK. Tetrahedron Lett.  1996,  37:  7445 

3d Graham AE. Taylor RJK. J. Chem. Soc., Perkin Trans. 1  1997,  1087 

3e Ragot JP. Steeneck C. Alcaraz M.-L. Taylor RJK. J. Chem. Soc., Perkin Trans. 1  1999,  1073 

3f Runcie KA. Taylor RJK. Org. Lett.  2001,  3:  3237 

4a Alcaraz L. Macdonald G. Ragot J. Lewis NJ. Taylor RJK. Tetrahedron  1999,  55:  3707 

4b Alcaraz L. Macdonald G. Ragot J. Lewis NJ. Taylor RJK. J. Org. Chem.  1998,  63:  3526 

4c Taylor RJK. Alcaraz L. Kapfer-Eyer I. Macdonald G. Wei X. Lewis NJ. Synthesis  1997,  775 ; and references therein

5 Macdonald G. Alcaraz L. Lewis NJ. Taylor RJK. Tetrahedron Lett.  1998,  39:  5433 

6 Dwyer CL. Gill CD. Ichihara O. Taylor RJK. Synlett  2000,  704 

7a Genski T. Macdonald G. Wei X. Lewis N. Taylor RJK. Synlett  1999,  795 

7b Genski T. Macdonald G. Wei X. Lewis N. Taylor RJK. Arkivoc  2000,  1:  266 

For recent reviews see:

8a Ishikawa T. Isobe T. Chem. Eur. J.  2002,  8:  553 

8b Schmidtchen FP. Berger M. Chem. Rev.  1997,  97:  1609 ; and references therein

For recent publications in the area of enantiopure guanidines see: Michael Additions:

9a Ishikawa T. Araki Y. Kumamoto T. Seki H. Fukuda K. Isobe T. Chem. Commun.  2001,  245 ; and references therein

9b Howard-Jones A. Murphy PJ. Thomas DA. Caulkett PWR. J. Org. Chem.  1999,  64:  1039 

9c Ma K. Cheng K. Tetrahedron: Asymmetry  1999,  10:  713 

10a Strecker Synthesis: Corey EJ. Grogan MJ. Org. Lett.  1999,  1:  157 

10b Henry Reaction: Chinchilla R. Nájera C. Sánchez-Agulló P. Tetrahedron: Asymmetry  1994,  5:  1393 

11 Yamamoto Y. Kojima S. In The Chemistry of Amidines and Imidates   Vol. 2:  Patai S. Rappoport Z. Wiley; New York: 1991. 

12a Kim KS. Qian L. Tetrahedron Lett.  1993,  34:  7677 

12b Levallet C. Lerpiniere J. Ko SY. Tetrahedron  1997,  53:  5291 

13

All new compounds were fully characterised by ¹H NMR, ¹³C NMR and IR spectroscopies plus HRMS or elemental analysis.

14a Baker TJ. Tomioka M. Goodman M. Org. Synth.  2000,  78:  91 

14b Zapf CW. Creighton CJ. Tomioka M. Goodman M. Org. Lett.  2001,  3:  1133 ; and references therein

Preparation of 8d·HCl salt:

15a

(S)-1-Methoxy-2-propyl-amine (2.59 g, 29.1 mmol) was added to a solution of N,N′-di-Boc-N′′-trifluoromethanesulfonylguanidine 6 (7.59 g, 19.4 mmol) and diisopropyl(ethyl)amine (5.1 cm³, 29.3 mmol) in CH₂Cl₂, under argon. The reaction was at r.t. for 2 h before the solvent was removed under reduced pressure and the residue was purified by flash silica chromatography (CH₂Cl₂) to give N,N′-di-Boc-N′′-[(1S)-2-methoxy-1-methylethyl]guanidine 7d (6.12 g, 95%) as a white solid, mp 79-80 °C; [α]_D ²⁰ -6.5 (c 1.0, CHCl₃) which was fully characterised.

15b

The Boc-protected guanidine 7d (6.05 g, 18.2 mmol) was dissolved in approx. 3 M anhyd methanolic HCl (100 cm³) and was stirred at 40 °C, under argon, for 18 h. The solvent was then removed under reduced pressure to afford N′′-[(1S)-2-methoxy-1-methylethyl]guanidine hydrochloride (8d·HCl) quantitatively (3.03 g) as a hygroscopic gum, [α]_D ²⁰ -24.3 (c 1.00, MeOH). IR (neat): ν_max: 3253 and 3147 (NH), 2981 and 2934 (CH), 1640 (CN₃) cm^-1. ¹H NMR (400 MHz, CD₃OD): δ = 3.84-3.79 (1 H, m, CH), 3.47 (1 H, dd, J = 9.5 and 4.0, CH_AH_BOMe), 3.40 (3 H, s, OCH₃), 3.37 (1 H, dd, J = 9.5 and 6.5, CH_AH_BOMe), 1.23 (3 H, d, J = 6.5, CH₃). ¹³C NMR (100 MHz, CD₃OD): δ_C = 158.3 (CN₃), 76.9 (CH), 59.4 (OCH₃), 48.5 (CH₂), 17.4 (CH₃). MS (CI): m/z = 132(100) [MH⁺]; HRMS (CI): Calcd for C₅H₁₄N₃O: 132.1137. Found: [MH⁺]: 132.1132 (2.7 ppm error).

16 The C₂-symmetric pyrrolidines were prepared according to: Yamamoto Y. Hoshino J. Fujimoto Y. Ohmoto J. Sawada S. Synthesis  1993,  298 

17 Guo Z.-X. Cammidge AN. Horwell DC. Synth. Commun.  2000,  30:  2933 ; and references therein

18

Chiral HPLC was carried out using a Chiralcel OJ column (25 cm × 4.6 mm) with hexane-isopropanol (98:2) as eluent at a flow rate of 1 mL/min and detection at 276 nm.