Self-Activation and 1,8-Stereoinduction in a Boronate-substituted Dienophile

Abstract

The [4+2] cycloaddition of ortho-boronoanilide dienophile 4 with cyclopentadiene was found to proceed faster than both its para isomer 8 and the unsubstituted derivative 6, thereby confirming that self-activation by internal coordination is operative in the case of 4. Chiral boronic esters derivatives 9 and 10 provided a small level of remote 1,8-stereoinduction. These results show that dialkoxyboronic esters can operate as weak, internal Lewis acids and activate carbonyl-containing functionalities in cycloaddition reactions.

Lewis acids - Diels-Alder reactions - substituent effects - chiral auxiliaries - stereoselective synthesis

References

1 Matteson DS. Allies PG. J. Organomet. Chem.  1973,  54:  35 

2a Diaryloxy or acyloxy boronic esters are more acidic and have been used in several catalysts for asymmetric synthesis. For a noticeable example on a dialkoxyboronic ester catalyst based on a tartrate substituent, see: Loh T.-P. Wang R.-B. Sim K.-Y. Tetrahedron Lett.  1996,  37:  2989 

2b

Tartrate boronic esters, however, are considered moderately activated by the electron-withdrawing ester groups.

3 For a review on remote stereoinduction, see: Mikami K. Shimizu M. Zhang H.-C. Maryanoff BE. Tetrahedron  2001,  57:  2917 

4 For a recent example of remote asymmetric induction using chiral boronates, see: Sailes HE. Watts JP. Whiting A. J. Chem. Soc., Perkin Trans. 1  2000,  3362 

5a

All compounds reported herein were obtained in a high state of purity and exhibited spectral data (NMR, MS) in accord with proposed structures. Characterization data for dienophile substrates 4, 6, 8: Pinacol ortho-boronoanilide 4: white solid, mp: 168-170 °C; ¹H NMR (Acetone-d ₆ , 400 MHz): δ = 10.34 (br s, 1 H), 8.06 (m, 1 H), 7.67 (d, J = 8 Hz, 1 H), 7.37 (m, 1 H), 7.10 (apparent t, J = 8 Hz, 1 H), 6.38 (m, 2 H), 5.82 (dd, J = 7 Hz, 5 Hz, 1 H), 1.38 (s, 12 H); ¹³C NMR (Acetone-d ₆ , 100 MHz): δ = 164.1, 143.6, 136.0, 135.9, 132.2, 131.8, 131.7, 127.9, 127.8, 124.6, 124.5, 119.0, 84.1, 84.0, 25.6, 25.5; ¹³C NMR (Benzene-d ₆ , 100 MHz): δ = 163.2, 145.3, 136.4, 133.1, 132.8, 125.8, 123.4, 119.6, 83.9, 24.8. A very slight peak duplication effect, ca. 0.05 ppm, was observed for arene carbons in acetone. This may be due to a slow competing effect from this coordinating solvent. ¹¹B NMR (Benzene-d ₆ , 64 MHz): δ = 30.1; IR (CH₂Cl₂ cast, cm^-1): 3316 (m, N-H), 3058 (w, Csp ²-H), 2970 (s, Csp ³-H), 1646 (s, C=O), 731 (s, o-sub Ar); HRMS (EI): m/z calcd for C₁₅H₂₀NO₃ ¹¹B: 273.15363; found: 273.15376. Acrylanilide 6: [5b] ¹H NMR (CDCl₃, 300 MHz): δ = 7.58 (m, 2 H), 7.31 (m, 2 H), 7.18 (br s, 1 H), 7.10 (m, 1 H), 6.43 (d, J = 17 Hz, 1 H), 6.25 (dd, J = 17 Hz, 10.2 Hz, 1 H), 5.78 (d, J = 10 Hz, 1 H). ¹³C (CDCl₃, 75 MHz): δ = 164.0, 140.2, 132.8, 129.5, 126.9, 124.4, 120.3. Pinacol para-boronoanilide 8: ¹H NMR (Acetone-d ₆ , 300 MHz): δ = 7.75 (AB, J = 9 Hz, 2 H), 7.68 (AB, J = 9 Hz, 2 H), 6.46 (dd, J = 17 Hz, 10 Hz, 1 H), 6.34 (dd, J = 16 Hz, 3 Hz, 1 H), 5.70 (dd, J = 10 Hz, 3 Hz, 1 H), 1.31 (s, 12 H); ¹³C NMR (Acetone-d ₆ , 100 MHz): δ = 164.1, 142.8, 136.3, 136.2 (broad weak signal, C-B), 132.7, 127.4, 119.2, 84.3, 25.2; ¹¹B NMR (Benzene-d ₆ , 64 MHz): δ = 30.8; IR (CH₂Cl₂ cast, cm^-1): 3303 (m, N-H), 3102 (w, Csp ²-H), 2978 (m, Csp ³-H), 1667 (s, C=O), 1635 (s, C=C alkyl), 1593 (s, C=C aromatic), 1361 (vs, B-O), 860 (m, p-sub Ar); HRMS (EI): m/z calcd for C₁₅H₂₀NO₃ ¹¹B: 273.15363, found: 273.15381.

5b Hegedus LS. Allen GF. Olsen DJ. J. Am. Chem. Soc.  1980,  10:  3583 

ortho-Aminophenylboronic acid can be obtained from various commercial sources or prepared according to:

6a Nitration: Seaman W. Johnson JR. J. Am. Chem. Soc.  1931,  53:  711 

6b Hydrogenation: Groziak MP. Ganguly AD. Robinson PD. J. Am. Chem. Soc.  1994,  116:  7597 ; the para-aminophenylboronic acid was obtained from Combi-Blocks

7

X-ray crystallographic data have been deposited to the Cambridge Crystallographic Data Centre (file number: CCDC 166880).

8 For an example of internally coordinated alpha-acetamidomethylboronate, see: Matteson DS. Michnick TJ. Willet RD. Patterson CD. Organometallics  1989,  8:  726