Expedient enantiospecific synthesis of RP 73613: A new selective non-peptide NK1 antagonist

The Conversion of Primary or Secondary Alcohols with Nonaflyl Fluoride into Their Corresponding Inverted Fluorides

“…On comparing the different modifications of fluorodehydroxylation conditions, the original procedure with NfF and DBU in its optimized version is the fastest and maybe also the most efficient procedure. 15,32 Yet it is obvious by now that fluorodehydroxylations of alcohols with NfF, either in combination with DBU 15 (particularly in its optimized version), 32 or in combination with diethylamine, 58 cyclohexyldimethylamine, 60 triethylamine plus triethylamine trihydrofluoride, 57,[61][62][63] or ethyldiisopropylamine plus ethyldiisopropylamine trihydrofluoride 61 will replace DAST 8 for both small-scale and, especially, large-scale fluorodehydroxylations of primary or secondary alcohols.…”

“…Subsequent to our publication that disclosed fluorodehydroxylations with NfF and DBU, 15 several industrial laboratories described reactions of primary and secondary alcohols with NfF in combination with DBU and triethylamine trihydrofluoride, 4 or with diethylamine 58 with cyclohexyldimethylamine 60 or with triethylamine in combination with triethylamine trihydrofluoride. 61 When treated with NfF and diethylamine in tetrahydrofuran, the secondary alcohol 57 gave the inverted fluoride 60 in 90% yield (Scheme 12).…”

“…61 When treated with NfF and diethylamine in tetrahydrofuran, the secondary alcohol 57 gave the inverted fluoride 60 in 90% yield (Scheme 12). 58 Since the combination of NfF and triethylamine was not effective, 15 Although excess neat diethylamine and trifluoromethanesulfonyl fluoride react instantly to form the sulfonamide 61, 59 diethylamine is apparently only partially N-sulfonated by NfF under the same reaction conditions to the nonaflate analogue of 61 (Scheme 12).…”

“…the desired Ononaflate (such as 59, Scheme 12) is possibly formed via a six-membered transition state (e.g., 58) that involves the hydroxy group, nonaflyl fluoride and diethylamine. Nucleophilic attack by diethylammonium fluoride19 on the O-nonaflate (e.g., 59) gives the desired inverted fluoride (e.g., 60, 90% yield58 ) along with varying amounts of the resulting sulfonamide.…”

Amine-Induced Decomposition of Perfluoroalkanesulfonyl Fluorides

“…4 In particular, nonaflyl fluoride has been applied to convert phenols into their phenol O-nonaflates 5,6 or O-silylated ketone enolates into their corresponding enol O-nonaflates, 7,8 all of which readily undergo Heck, [9][10][11] Suzuki, [12][13][14] or Sonogashira 15,16 reactions. Primary or secondary aliphatic hydroxy groups are transformed (fluorodehydroxylated) by NfF in the presence of 1,8diazabicyclo[5.4.0]undec-7-ene (DBU), 17 diethylamine, 18 N-cyclohexyldimethylamine, 19 or triethylamine and triethylamine trihydrofluoride 20 in solvents such as toluene, methyl tert-butyl ether, tetrahydrofuran, or ethyl acetate to afford the corresponding primary or inverted secondary fluorides in up to 90% yield.…”