Consecutive biocatalysis-palladium catalysis II: Synthesis of conduritol-alkyne conjugates

Abstract

The palladium-catalyzed cross-coupling reaction of potassium alkynyltrifluoroborates with a chemoenzymatically derived deoxyconduritol is described. Six new compounds were synthesized in moderate to good yields. The alkynyl cross-coupling reaction can be effected using 10 mol% of Pd(PPh₃)₄ as catalyst in toluene–H₂O in the presence of Cs₂CO₃ as the inorganic base.

Introduction

During the last 20 years, Suzuki–Miyaura cross-coupling reactions have provided preparative methods for efficiently creating carbon–carbon bonds. The coupling reactions of aryl-, alkyl-, and alkenylboron compounds have been extensively investigated [2], [3]. However, the coupling of alkynylboron compounds has been limited to B-alkynyl-9-BBN borate complexes [4], alkynyltrialkoxyborate complexes [5] and lithium 1-alkynyl(triisopropoxy)borates [6].

Recently the use of potassium alkynyltrifluoroborates in carbon–carbon bond forming reactions has attracted significant attention owing to their stability and accessibility [7], [8], [9]. Darses et al. were the first to describe the preparation of potassium alkynyltrifluoroborates [7], [10], [11], [12] and 6 years ago Molander and co-workers reported their use in cross-coupling reactions with various aryl bromides obtaining excellent results [8]. In 2005, Kabalka et al. developed an efficient synthesis of cross-conjugated mono-enediynes using the cross-coupling of potassium alkynyltrifluroborates with 1,1-dibromo-1-alkenes in the presence of PdCl₂(dppf)CH₂Cl₂ [13].

Last year, our laboratories demonstrated the feasibility of the cross-coupling reaction of potassium aryltrifluoroborates with a deoxyconduritol in the presence of Pd(PPh₃)₄ as catalyst [1]. Though, in connection with our ongoing studies, we report in this article the palladium-catalyzed Suzuki cross-coupling reaction carried out with potassium alkynyltrifluoroborates that expands the scope of the coupling methodology.

In 1992, Hudlicky and Boros had described the use of terminal acetylenes in the Sonogashira coupling reaction with cis-3-bromocyclohexa-3,5-diene-1,2-diol [14]. This is, to the best of our knowledge, the only previous report on the use of these bacterial metabolites or their derivatives as partners in an alkyne–alkene coupling reaction. In the quest for an expansion on this palladium-catalyzed cross-coupling and considering organotrifluoroborates excellent nucleophiles, we used the corresponding alkynyl salts to accommodate a wide range of coupling partners into a deoxyconduritol moiety.