title: Atom-Economical Dimerization Strategy by the Rhodium-Catalyzed Addition of Carboxylic Acids to Allenes: Protecting-Group-Free Synthesis of Clavosolide A and Late-Stage Modification.
abstract: Natural products of polyketide origin with a high level of symmetry, in particular C2 -symmetric diolides as a special macrolactone-based product class, often possess a broad spectrum of biological activity. An efficient route to this important structural motif was developed as part of a concise and highly convergent synthesis of clavosolide A. This strategy features an atom-economic "head-to-tail" dimerization by the stereoselective rhodium-catalyzed addition of carboxylic acids to terminal allenes with the simultaneous construction of two new stereocenters. The excellent efficiency and selectivity with which the C2 -symmetric core structures were obtained are remarkable considering the outcome under classical dimerization conditions. Furthermore, this approach facilitates late-stage modification and provides ready access to potential new lead structures.
authors.affiliation: Institut für Organische Chemie, Albert-Ludwigs-Universität Freiburg, Albertstrasse 21, 79104 Freiburg im Breisgau (Germany).
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Haydl
authors.affiliation: Institut für Organische Chemie, Albert-Ludwigs-Universität Freiburg, Albertstrasse 21, 79104 Freiburg im Breisgau (Germany). bernhard.breit@chemie.uni-freiburg.de.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Breit
mesh_terms: D000466:Alkadienes / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry*; D002384:Catalysis; D019281:Dimerization; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D012238:Rhodium / Q000737:chemistry*
chemical_list: D000466:Alkadienes; D002264:Carboxylic Acids; D018942:Macrolides; C455699:clavosolide A; C025947:propadiene; D012238:Rhodium
keywords: allenes; allylic compounds; natural products; rhodium; total synthesis