Stereodivergent trifluoromethylation of N-sulfinylimines by fluoroform with either organic-superbase or organometallic-base

Abstract

Here we have successfully demonstrated the first stereodivergent direct nucleophilic trifluoromethylation of N-sulfinylimines using the potent greenhouse gas "HFC-23, fluoroform" with an organic-superbase or an organometallic-base in high yields and selectivity.

Organic Superbases in Recent Synthetic Methodology Research

“…[45] Concurrent with these developments, a variety of conditions employing inexpensive inorganic bases for HCF 3 activation were also reported [46] . Recently, Shibata discovered stereodivergence in the base‐promoted addition of HCF 3 to chiral N ‐sulfinyl imine electrophiles [47a] . The use of KHMDS conditions developed by Prakash promotes addition to the opposite face of the imine compared to use of P 4 ‐ t Bu, a result explained through a chelated or non‐chelated addition transition state, respectively.…”

Chiral N‐tert‐Butylsulfinyl Imines: New Discoveries

“…Imines 16 are trifluoromethylated with fluoroform and KHMDS at low temperature, to give the corresponding amines 105 (Scheme 45). [64] Interestingly, when instead of KHMDS a P 4 ‐ t ‐Bu was used as base, the opposite configuration was obtained for compounds 105 starting from the same materials, and using the same reaction conditions. Transition states TSI and TSII could explain the observed stereochemistry in compounds 105 .…”

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

“…Rather than decomposing CF 3 compounds, it would be better to maximize the efficiency of their use [16][17][18]. However, taming HCF 3 as a trifluoromethylation agent is a challenge in organic chemistry [19][20][21][22][23][24][25][26][27][28], although recent rapid progress in the chemistry of HCF 3 by Grushin (for CuCF 3 ) [29][30][31][32][33][34][35][36][37], Prakash (for KCF 3 ) [38], and others [39][40][41][42][43][44], including our group [45][46][47][48][49][50], has dramatically improved the prospects. One of the problems facing the treatment of HCF 3 for nucleophilic trifluoromethylation reactions is the low stability of the directly generated CF 3 anion (CF 3 − ) for decomposing to difluorocarbene (:CF 2 ) and fluoride (F − ) (Scheme 1a).…”