Combining two-directional synthesis and tandem reactions. Part 21: Exploitation of a dimeric macrocycle for chain terminus differentiation and synthesis of an sp3-rich library

The application of a tandem condensation/cyclisation/[3+2]-cycloaddition/elimination reaction gives an sp3-rich tricyclic pyrazoline scaffold with two ethyl esters in a single step from a simple linear starting material. The successive hydrolysis and cyclisation (with Boc anhydride) of these 3-dimensional architectures, generates unprecedented 16-membered macrocyclic bisanhydrides (characterised by XRD). Selective amidations could then be achieved by ring opening with a primary amine followed by HATU-promoted amide coupling to yield an sp3-rich natural product-like library

Facile access to a heterocyclic, sp3-rich chemical scaffold via a tandem condensation/intramolecular nitrone–alkene [3+2] cycloaddition strategy

A heterocyclic, sp3-rich chemical scaffold was synthesised in just 6 steps via a highly regio- and diastereo-selective tandem nitrone formation/intramolecular nitrone–alkene [3+2] cycloaddition reaction. A library of 543 lead-like compounds based on the scaffold core has been produced

Discovery and development of 3,3,3-trichloropropyl-1-triphenylphosphonium chloride: A reagent for synthesis of Z-1,3-enynes, Z,Z-1-chloro-1,3-dienes and 1,3-diynes

Reported herein are the discovery and development of 3,3,3-Trichloropropyl-1-triphenylphosphonium chloride, a 3-carbon homologation reagent for the synthesis of Z-1,3-Enynes, Z,Z-1-Chloro-1,3-Dienes and 1,3-Diynes. Pertinent highlights are (1) Development of a cost effective and efficient method for the synthesis of the 3-carbon reagent. (2) Application to the synthesis of 1,3-Enynes, Z,Z-1-choro-1,3-Dienes and 1,3-Diyne. (3) Studies directed towards the total synthesis of Leustroducsin H. (4) Total synthesis of (±)-Histrionicotoxin

Synthesis of natural-product-like scaffolds in unprecedented efficiency via a 12-fold branching pathway

Tying the knot! The marriage of two-directional synthesis and tandem reactions allows access to twelve skeletally diverse scaffolds in just fifteen reactions. Two-directional synthesis yields a symmetrical linear “rope-like” keto-dienoate which is then subjected to twelve separate tandem reactions to “tie the rope in knots” thus creating twelve diverse natural product-like scaffolds containing useful functionality for further elaboration