Highly Enantioselective Simmons–Smith Fluorocyclopropanation of Allylic Alcohols via the Halogen Scrambling Strategy of Zinc Carbenoids

Abstract

Highly enantio- and diastereoenriched monofluorocyclopropanes were accessed via the Simmons-Smith fluorocyclopropanation of allylic alcohols using difluoroiodomethane and ethylzinc iodide as the substituted carbenoid precursors. The scrambling of halogens at the zinc carbenoid led to the formation of the fluorocyclopropanating agent (fluoroiodomethyl)zinc(II) fluoride. This strategy circumvented the ongoing limitation in Simmons-Smith fluorocyclopropanations relying on the use of the relatively inaccessible and expensive carbenoid precursor fluorodiiodomethane.

Homologation chemistry with nucleophilic α-substituted organometallic reagents: chemocontrol, new concepts and (solved) challenges

“…On the other hand, the corresponding magnesium fluorocarbenoids generated via sulfoxide-magnesium exchange suffered from halogen-scrambling similarly to zinc fluorocarbenoids noticed by Charette. 92 However, these results further confirm the existence of LiCH 2 F, though it appears evident that neither tin-nor sulfoxidefluoromethylstannanes are the ideal carbenoid precursors (Scheme 23). An effective solution was finally found by adopting a highly effective iodine-lithium exchange on the currently commercially available and easy to manipulate (liquid, bp 53 1C) fluoroiodomethane (Scheme 24).…”

Key Mechanistic Features in Palladium-Catalyzed Methylcyclopropanation of Norbornenes With Vinyl Bromides: Insights From DFT Calculations

“…Cyclopropane skeleton has attracted tremendous attention from organic chemists and can be found in many important biomolecules and pharmaceutical drugs (Hofmann et al, 1954; Crowley et al, 1961; Wiberg, 1996; de Meijere, 2003; Fedorynski, 2003; Lebel et al, 2003; Pietruszka, 2003; Reissig and Zimmer, 2003; Wessjohann et al, 2003; Hata et al, 2011; Chen et al, 2014; Hiratsuka et al, 2014). Many methods have been used to construct the cyclopropane scaffold, including transition metal mediated C–C and C–H bond activations (Satake and Nakata, 1998; Goudreau and Charette, 2010; Oonishi et al, 2012; Masutomi et al, 2014; Du et al, 2015), carbene/carbenoid cycloadditions (Miki et al, 2002; Biswas et al, 2012; Lindsay et al, 2013), Simmons–Smith reactions (Simmons and Smith, 1958; Beaulieu et al, 2013), Michael-initiated ring closure (MIRC) (Xie et al, 2007; Xuan et al, 2009), cycloisomerizations (Bruneau, 2005; Miege et al, 2011), and the coupling of norbornenes with organoboron reagents or alkynes (Bigeault et al, 2005; Miura et al, 2006).…”

A Two‐Step Sequence to Ethyl α‐Fluorocyclopropanecarboxylates Through MIRC Reaction of Ethyl Dichloroacetate and Highly Regioselective Fluorination

“…Jubault et al10 reported the reaction of ethyl dibromofluoroacetate with electron‐deficient olefins in the presence of diethylzinc or Zn/LiCl, and Hu et al11 developed the first chiral monofluoromethylenation reagent, ( R )‐ N ‐tosyl‐ S ‐fluoromethyl‐S‐phenylsulfoximine, for the synthesis of chiral monofluorinated cyclopropanes. Very recently, Charette et al12 reported the highly enantioselective Simmons‐Smith fluorocyclopropanation of allylic alcohols by using difluoroiodomethane and ethylzinc iodide as the substituted carbenoid precursors. Although the utility of existing methods was demonstrated by the synthesis of several types of biologically active compounds, the fluorine sources they used are rather limited.…”