title: Iterative protecting group-free cross-coupling leading to chiral multiply arylated structures.
abstract: The Suzuki-Miyaura cross-coupling is one of the most often utilized reactions in the synthesis of pharmaceutical compounds and conjugated materials. In its most common form, the reaction joins two sp(2)-functionalized carbon atoms to make a biaryl or diene/polyene unit. These substructures are widely found in natural products and small molecules and thus the Suzuki-Miyaura cross-coupling has been proposed as the key reaction for the automated assembly of such molecules, using protecting group chemistry to affect iterative coupling. We present herein, a significant advance in this approach, in which multiply functionalized cross-coupling partners can be employed in iterative coupling without the use of protecting groups. To accomplish this, the orthogonal reactivity of different boron substituents towards the boron-to-palladium transmetalation reaction is exploited. The approach is illustrated in the preparation of chiral enantioenriched compounds, which are known to be privileged structures in active pharmaceutical compounds.
authors.affiliation: Queen's University, Department of Chemistry, Chernoff Hall, Kingston, Ontario, Canada K7L 3N6.|Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Chikusa, Nagoya 464-8602, Japan.
authors.forename: Cathleen M
authors.initials: CM
authors.lastname: Crudden
authors.affiliation: Queen's University, Department of Chemistry, Chernoff Hall, Kingston, Ontario, Canada K7L 3N6.
authors.forename: Christopher
authors.initials: C
authors.lastname: Ziebenhaus
authors.affiliation: Queen's University, Department of Chemistry, Chernoff Hall, Kingston, Ontario, Canada K7L 3N6.
authors.forename: Jason P G
authors.initials: JP
authors.lastname: Rygus
authors.affiliation: Queen's University, Department of Chemistry, Chernoff Hall, Kingston, Ontario, Canada K7L 3N6.
authors.forename: Kazem
authors.initials: K
authors.lastname: Ghozati
authors.affiliation: Queen's University, Department of Chemistry, Chernoff Hall, Kingston, Ontario, Canada K7L 3N6.
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Unsworth
authors.affiliation: Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University, Chikusa, Nagoya 464-8602, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Nambo
authors.affiliation: Queen's University, Department of Chemistry, Chernoff Hall, Kingston, Ontario, Canada K7L 3N6.
authors.forename: Samantha
authors.initials: S
authors.lastname: Voth
authors.affiliation: Queen's University, Department of Chemistry, Chernoff Hall, Kingston, Ontario, Canada K7L 3N6.
authors.forename: Marieke
authors.initials: M
authors.lastname: Hutchinson
authors.affiliation: Queen's University, Department of Chemistry, Chernoff Hall, Kingston, Ontario, Canada K7L 3N6.
authors.forename: Veronique S
authors.initials: VS
authors.lastname: Laberge
authors.affiliation: Queen's University, Department of Chemistry, Chernoff Hall, Kingston, Ontario, Canada K7L 3N6.|Department of Chemistry and Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Maekawa
authors.affiliation: Queen's University, Department of Chemistry, Chernoff Hall, Kingston, Ontario, Canada K7L 3N6.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Imao