Palladium-Catalyzed Stereoconvergent Formylation of (E/Z)-β-Bromo-β-fluorostyrenes: Straightforward Access to (Z)-α-Fluorocinnamic Aldehydes and (Z)-β-Fluorocinnamic Alcohols

Abstract

We report here the stereoconvergent formylation of (E/Z)-β-bromo-β-fluorostyrene mixtures with carbon monoxide and sodium formate catalyzed by palladium. Optimization of reaction conditions leads to the corresponding pure (Z)-α-fluorocinnamaldehydes in good yields. The reaction was extended to styrenes bearing electro-attracting or electro-donating groups. The obtained α-fluoroaldehydes were smoothly reduced to the corresponding (Z)-β-fluorocinnamic alcohol by NaBH(4). The reaction could be performed on functionalized substrates as demonstrated by the access to the glucoside of β-fluoroconiferyl alcohol, (Z)-β-fluoroconiferin, a strong inhibitor of lignin polymerization.

One‐Pot l‐Proline‐Mediated Stereoselective α‐C(sp2)–H Fluorination of α,β‐Unsaturated Aldehydes through Methoxyfluorination–Elimination

“…Isolated yield, the stereochemistry was determined by comparing chemical shifts (CH, CH 2 and CF) and J values ( 3 J HF of CF/CH and 3 J HF of CF/CH 2 ), obtained by 19 F and 1 H NMR spectroscopy, with the references , …”

“…The direct approaches for the preparation of 2‐fluoropropenals are based on the reaction of β‐fluorovinamidinium salts with Grignard reagents,[10a] hydrolysis of aryl‐substituted α,β‐difluoroallyl alcohols,[10b] or treatment of Weinreb amides with DIBAL‐H. [10c] In 2011, Rolando reported a strategy for the synthesis of α‐fluoro‐conjugated aldehydes based on the palladium‐catalyzed formylation of α‐bromo‐α‐fluoroolefins, obtained by a Wittig–Burton reaction, with carbon monoxide (Scheme a) . However, most of these procedures generally suffer from several major drawbacks including the requirement of metal catalysts, harsh reaction conditions, and the use of expensive or complex starting materials.…”

“…tained by a Wittig-Burton reaction, with carbon monoxide (Scheme 1a). [11] However, most of these procedures generally suffer from several major drawbacks including the requirement of metal catalysts, harsh reaction conditions, and the use of expensive or complex starting materials. Scheme 1.…”

“…Scope of substrates. CH 2 and CF) and J values ( 3 J HF of CF/CH and 3 J HF of CF/CH 2 ), obtained by19 F and 1 H NMR spectroscopy, with the references [11,…”

Synthesis of Monofluoroalkenes: A Leap Forward

“…The Rolando group also developed the palladium-catalyzed formylation of β-bromo-β-fluorostyrenes to access (Z)-α-fluorocinnamaldehydes (Scheme 116). 130 The reaction showed good yields and excellent stereoselectivity, but the (E)-α-fluoroalkene was always observed as a side product. Subsequent reduction of the (Z)-α-fluorocinnamaldehydes using NaBH 4 gave the corresponding (Z)-β-fluorocinnamic alcohols.…”