1240815-92-2Relevant academic research and scientific papers
Stereocontrolled synthesis of adjacent acyclic quaternary-tertiary motifs: Application to a concise total synthesis of (-)-filiformin
Blair, Daniel J.,Fletcher, Catherine J.,Wheelhouse, Katherine M. P.,Aggarwal, Varinder K.
, p. 5552 - 5555 (2014)
Lithiation/borylation methodology has been developed for the synthesis of acyclic quaternary-tertiary motifs with full control of relative and absolute stereochemistry, thus leading to all four possible isomers of a stereodiad. A novel intramolecular Zweifel-type olefination enabled acyclic stereocontrol to be transformed into cyclic stereocontrol. These key steps have been applied to the shortest enantioselective synthesis of (-)-filiformin to date (9 steps) with full stereocontrol. True to (fili)form: Lithiation/borylation methodology has been developed for the synthesis of acyclic quaternary-tertiary motifs with full control of relative and absolute stereochemistry, thus leading to all four possible isomers of a stereodiad. A novel intramolecular Zweifel-type olefination enabled acyclic stereocontrol to be transformed into cyclic stereocontrol. These key steps were applied to the enantioselective synthesis of (-)-filiformin.
Development of Enantiospecific Coupling of Secondary and Tertiary Boronic Esters with Aromatic Compounds
Odachowski, Marcin,Bonet, Amadeu,Essafi, Stephanie,Conti-Ramsden, Philip,Harvey, Jeremy N.,Leonori, Daniele,Aggarwal, Varinder K.
supporting information, p. 9521 - 9532 (2016/08/12)
The stereospecific cross-coupling of secondary boronic esters with sp2 electrophiles (Suzuki-Miyaura reaction) is a long-standing problem in synthesis, but progress has been achieved in specific cases using palladium catalysis. However, related couplings with tertiary boronic esters are not currently achievable. To address this general problem, we have focused on an alternative method exploiting the reactivity of a boronate complex formed between an aryl lithium and a boronic ester. We reasoned that subsequent addition of an oxidant or an electrophile would remove an electron from the aromatic ring or react in a Friedel-Crafts-type manner, respectively, generating a cationic species, which would trigger 1,2-migration of the boron substituent, creating the new C-C bond. Elimination (preceded by further oxidation in the former case) would result in rearomatization giving the coupled product stereospecifically. Initial work was examined with 2-furyllithium. Although the oxidants tested were unsuccessful, electrophiles, particularly NBS, enabled the coupling reaction to occur in good yield with a broad range of secondary and tertiary boronic esters, bearing different steric demands and functional groups (esters, azides, nitriles, alcohols, and ethers). The reaction also worked well with other electron-rich heteroaromatics and 6-membered ring aromatics provided they had donor groups in the meta position. Conditions were also found under which the B(pin)- moiety could be retained in the product, ortho to the boron substituent. This protocol, which created a new C(sp2)-C(sp3) and an adjacent C-B bond, was again applicable to a range of secondary and tertiary boronic esters. In all cases, the coupling reaction occurred with complete stereospecificity. Computational studies verified the competing processes involved and were in close agreement with the experimental observations.
Full chirality transfer in the conversion of secondary alcohols into tertiary boronic esters and alcohols using lithiation-borylation reactions
Bagutski, Viktor,French, Rosalind M.,Aggarwal, Varinder K.
supporting information; experimental part, p. 5142 - 5145 (2010/10/20)
New conditions, full transfer: Using MgBr2/MeOH as an additive now provides essentially 100 % retention of configuration in the lithiation-borylation reaction, thus leading to tertiary boronic esters (or tertiary alcohols) with exceptionally hi
