Stereoselective Synthesis of Dienyl-Carboxylate Building Blocks: Formal Synthesis of Inthomycin C

Abstract

A direct synthesis of stereodefined halodienes is reported. Those key building blocks enable a concise access to polyenic products, as demonstrated in a modular synthesis of Inthomycin C.

Developing piperine towards TRPV1 and GABAA receptor ligands – synthesis of piperine analogs via Heck-coupling of conjugated dienes

“…An extension of the reaction time was not attempted in these cases, since the mass balance indicated significant decomposition of the starting materials. First, a set of four bases (NEt 3 , NaHCO 3 , K 2 CO 3 and NaOAc) and four solvents (MeCN, toluene, THF and DMF) were evaluated (entries [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. While toluene and THF did not facilitate coupling in combination with most bases, the best results were obtained with DMF as the solvent (entries 15-18).…”

“…Coupling proceeded smoothly for a variety of aryl bromides bearing electron donating (4, 6-9) or electron withdrawing substituents (12)(13)(14)(15). In the reactions of bromochlorobenzenes the chloro-substituent was inert under the reaction conditions (10 and 11).…”

“…Compared to other protocols, the use of arylbromides instead of boronic acids, 13 alkynes, 11 alkenes 10 or aldehydes 8 comprises a significant advantage in terms of price and commercial availability. Applying this protocol we have synthesized a library of 15 compounds.…”

Towards a Scalable Synthesis of 2‐Oxabicyclo[2.2.0]hex‐5‐en‐3‐one Using Flow Photochemistry

“…Within this family of compounds bicyclic cyclobutene lactones, such as 2‐oxabicyclo[2.2.0]hex‐5‐en‐3‐one 2 , are of particular synthetic use, since they also allow functionalization by initial nucleophilic attack from a diverse range of nucleophiles, opening the lactone ring. This reactivity has been demonstrated with halides (Scheme a), as well as various soft and hard nucleophiles . Heteroatomic (O− and N− based) nucleophiles, on the other hand, have been demonstrated to induce a spontaneous ring opening in a highly stereocontrolled manner, to furnish the diene product (Scheme b) .…”

“…Indeed, it has been demonstrated that all four enantiomers of the resulting monocyclic cyclobutene can be accessed by diastereodivergent deracemization with exceptional enantiocontrol (Scheme c) . Furthermore, the cyclobutene portion of the molecule can be invoked in other complexity‐generating synthetic steps, such as carbene insertion or cross‐coupling reactions of the linear diene product . Consequently, these and related cyclobutenes and cyclobutane derivatives have been utilized as key intermediates in numerous natural product syntheses,, and, therefore, robust and scalable methods for their preparation are of great interest to many members of the synthetic organic chemistry community.…”