A Metal-Free Cycloaddition Approach to Highly Substituted Aromatic Boronic Esters

Abstract

Alkynylboronates participate in [4+2] benzannulation reactions to furnish highly functionalised aromatic boronic esters, further manipulation of these boronic esters has been achieved via oxidation and Suzuki coupling reactions.

Keywords

cycloaddition - alkynylboronates - regioselective - aromatic boronic esters

References

• 1a Davies MW. Johnson CN. Harrity JPA. Chem. Commun.  1999,  2107 
• 1b Davies MW. Johnson CN. Harrity JPA. J. Org. Chem.  2001,  66:  3525 
• 1c Davies MW. Wybrow RAJ. Johnson CN. Harrity JPA. Chem. Commun.  2001,  1558 
• 1d Moore JE. Goodenough KM. Spinks D. Harrity JPA. Synlett  2002,  2071 
• For previous [4+2] cycloaddition reactions of alkynylboronates see:
• 2a Hilt G. Smolko KI. Angew. Chem. Int. Ed.  2003,  42:  2795 
• 2b Matteson DS. Waldbillig JO. J. Org. Chem.  1963,  28:  366 
• 2c Woods WG. Strong PL. J. Organomet. Chem.  1967,  7:  371 
• 3a Ogliaruso MA. Romanelli MG. Becker EI. Chem. Rev.  1965,  65:  261 
• 3b Allen CF. Van Allan JA. J. Am. Chem. Soc.  1950,  72:  5165 
• 3c Merlet S. Birau M. Wang ZY. Org. Lett.  2002,  4:  2157 
• 3d White DM. J. Org. Chem.  1974,  39:  1951 
• 5a Thompson LA. Ellman JA. Chem. Rev.  1996,  96:  555 
• 5b Suzuki A. Pure Appl. Chem.  1994,  66:  213 
• 5c Miyaura N. Suzuki A. Chem. Rev.  1995,  95:  2457 

4

Regiochemical assignments in compounds 8, 9, 10, 13 were carried out by NOE spectroscopy.

6

Representative Experimental Procedure for Alkynylboronate Cycloaddition Reactions: Synthesis of 4′-Butyl-5′-{4,4,5,5-tetramethyl-[1,3,2,]dioxaborolan-2-yl}-[1,1′,2′,1′′]terphenyl-3′,6′-dicarboxylic Acid Dimethyl Ester (7b). 2-Oxo-4,5-diphenyl-cyclopenta-3,5-diene-1,3-dicarboxylic acid dimethyl ester (1, 460 mg, 1.32 mmol) was weighed into a round-bottomed flask together with 2-hex-1-ynyl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (6b, 200 mg, 0.096 mmol). The flask was fitted with a reflux condenser and mesitylene (1 mL) was added. The resulting orange solution was stirred for 16 h at 160 °C under nitrogen. The dark brown reaction mixture was cooled to r.t., and purified by flash column chromatography (eluting solvent CH₂Cl₂-MeOH, 50:1 ratio) to give the title compound as a pale yellow solid (299 mg, 59% yield). Mp 123-125 °C. ¹H NMR (250 MHz, CDCl₃): δ = 0.85 (3 H, t, J = 7.0 Hz), 1.30 (12 H, s), 1.11-1.42 (2 H, m), 1.48-1.66 (2 H, m), 2.70 (2 H, t, J = 8.5 Hz), 3.30 (3 H, s), 3.33 (3 H, s), 6.52-6.79 (4 H, m), 6.93-7.05 (6 H, m). ¹³C NMR (62.9 MHz, CDCl₃): δ = 13.9, 23.3, 25.1, 33.8, 35.1, 51.6, 51.7, 84.3, 126.5, 126.8, 127.1, 127.2, 129.9, 130.2, 136.4, 136.7, 138.3, 138.6, 139.4, 140.4, 143.4, 169.6, 170.7. FT-IR (CHCl₃): 2954 (w), 1731 (s), 1562 (w), 1436 (m), 1361 (s), 1322 (s) cm^-1. HRMS: m/z calcd for C₃₂H₃₇BO₆: 528.2683; found: 528.2684. Anal. Calcd for C₃₂H₃₇BO₆: C, 72.73; H, 7.06. Found: C, 72.88; H, 7.01.