Synthesis of oxygen-containing heterocyclic compounds via α-chloro-δ-(trimethylsilyloxy)imines

1-Azaallylic Anions in Heterocyclic Chemistry

“…78 This conversion into 2,3-disubstituted tetrahydropyrans 351 bears similarity with the formation of cis-2-alkoxy-3-aminotetrahydrofurans 177 from γ-trimethylsilyloxy-R-chloroketimines 175, where no competitive intramolecular nucleophilic substitution occurred because of ring strain (vide supra). 79 Again the mechanism was explained via two equally plausible pathways.…”

“…76 Regiospecific deprotonation of R-chloroketimines 168 with lithium diisopropylamide, followed by alkylation with 3-bromopropyl trimethylsilyl ether (170), afforded the δ-trimethylsilyloxy-R-chloroketimines 171 (Scheme 35). 77,78 Reaction of the R-chloroketimines 171 with potassium tert-butoxide furnished mostly the 2-functionalized tetrahydrofurans 172, next to a substantial amount of 1-(alkylamino)-6-methyl-2-oxabicyclo[4.1.0]heptanes 173, the latter being the trapping products of the Favorskii intermediates, i.e., cyclopropylidenamines (nitrogen analogues of cyclopropanones). The furans 172 resulted from deprotection of the trimethylsilyl ether and subsequent intramolecular nucleophilic substitution.…”

“…When the δ-trimethylsilyloxy-R-chloroketimines 171 were reacted with methanol in the presence of bases, 2-alkoxy-3-aminotetrahydropyrans were formed, as well as tetrahydrofurans 172 (vide infra, Scheme 66). 78 The γ-trimethylsilyloxy-R-chloroketimines 175 cyclized with alcohols to afford cis-2-alkoxy-3-aminotetrahydrofurans 177 in a stereospecific way after treatment with base (Scheme 36). 79 The mechanism was explained in terms of two possible routes involving either a trans-2-amino-3-chlorotetrahydrofuran, (184) with lithium diisopropylamide produced the 3,3-dichloro-1-azaallylic anion 185, which reacted with 2-bromoethyl trimethylsilyl ether (174), resulting in the R,R-dichloroimine 186, the acidic hydrolysis of which gave 3,3-dichloro-2-hydroxy-2-phenyloxolane 187 (Scheme 38).…”

“…Both mechanisms lead to the same bicyclic aziridine 357, which suffers ring opening to the oxonium ion 358, which undergoes a stereospecific attack of the alcohol to provide cis-3-alkylamino-2-methoxytetrahydropyrans 351. 78 …”

Asymmetric Synthesis of Cyclopropylamines Starting from N-Sulfinyl α-Chloro Ketimines

“…From earlier research, it is known that the synthesis of cyclopropylamines can be achieved in acceptable yield upon treatment of N -alkyl α - halo imines with alkoxides . However, the cyclopropylamine synthesis via reaction of Grignard reagents with α - halo imines is unprecedented.…”