Titanium mediated asymmetric aldol reaction with α-fluoropropionimide enolates

Efficient Stereo-Selective Fluorination on Vitamin D3 Side-Chain Using Electrophilic Fluorination

“…However, this route yielded only the (22R)-fluoro product (21); efficient cationic fluorination of the (22S)-fluoro counterpart to yield the (22R)-CD-ring ( 11) has yet to be explored (Scheme 4). To overcome these drawbacks in order to introduce C24-and C22-monofluoro moieties, here we describe an alternative stereo-selective fluorination methodology at these positions via electrophilic fluorination using an Evans chiral auxiliary-based aldol reaction with NFSI [27][28][29].…”

Titanium Enolate Chemistry at the Beginning of the 21st Century

“…It was found that N ‐(α‐fluoropropyl)‐2‐(4 S )‐oxazolidinones generated ( E )‐enolates. Their addition to aldehydes resulted in the formation of α‐fluoro‐β‐hydroxyaldols with the fluorine and hydroxy groups placed anti to each other 32. It was noted that some α‐substituents capable of interacting with titanium(IV) ion were able to invert the stereochemistry of the aldol formation.…”

A Highly Regio- and Stereoselective Synthesis of α-Fluorinated Imides via Fluorination of Chiral Enamides

“…Given the number of impressive examples of enantioselective fluorinations being reported over the last decade, 6 asymmetric fluorinations represent an area of immense interest from the synthetic community. In relevance to our work, Davis 7 reported an elegant synthesis of α-fluoro-imides using enolate derived from chiral imide 1 substituted with chiral oxazolidinone auxiliary 8 ( 1→2 in Scheme 1). Our longstanding interest in the chemistry of enamides has drawn us to develop stereoselective fluorination methods using chiral enamides, 9 which has remained elusive.…”