An enantioselective addition of alkenylboronic acids and alkynylboronic esters to unprotected indole-appended enones is reported. This transformation proceeds with high enantioselectivity and high product yields via the use of catalytic amounts of 3,3'-bis(pentafluorophenyl)-BINOL and Mg(Ot-Bu)(2). A range of α-branched indole derivatives are available from the transformation.

A strategy allowing both stereocontrol and control over structural isomer formation has been defined for the antimalarial flindersial alkaloids. The recently reported flinderoles were demonstrated to be derived from the natural product borrerine. The structural isomers of flinderoles, the borreverines, were also produced in vitro along with the flinderoles through the dimerization of borrerine in acidic conditions. This result is thought to replicate the biosynthesis of these compounds. Flinderoles A, B, and C, desmethylflinderole C, isoborreverine, and dimethylisoborreverine can each be synthesized in three steps from tryptamine. Furthermore, progress toward a concise enantioselective synthesis of flinderoles A, B, and C is described. This work includes enantioselective conjugate addition to an unprotected indole-appended enone.

Two key factors bear on reaction rates for the conjugate addition of alkenyl boronic acids to heteroaryl-appended enones: the proximity of inductively electron-withdrawing heteroatoms to the site of bond formation and the resonance contribution of available heteroatom lone pairs to stabilize the developing positive charge at the enone β-position. For the former, the closer the heteroatom is to the enone β-carbon, the faster the reaction. For the latter, greater resonance stabilization of the benzylic cationic charge accelerates the reaction. Thus, reaction rates are increased by the closer proximity of inductive electron-withdrawing elements, but if resonance effects are involved, then increased rates are observed with electron-donating ability. Evidence for these trends in isomeric substrates is presented, and the application of these insights has allowed for reaction conditions that provide improved reactivity with previously problematic substrates.

Enantioselective Conjugate Addition of Alkenylboronic Acids to Indole-Appended Enones. -It is found that (R)-3,3'-I2-BINOL and the derivative (R)-BIN efficiently promote the title reaction. Asymmetric addition of alkynylboronic esters is also possible. -(LUNDY, B. J.; JANSONE-POPOVA, S.; MAY*, J. A.; Org. Lett. 13 (2011) 18, 4958-4961, http://dx.doi.org/10.1021/ol2020847 ; Dep. Chem., Univ. Houston, Houston, TX 77204, USA; Eng.) -Jannicke 03-096