CYCLZATION OF Ω-Halonitriles WITH ORGANOLITHIUMS

Short Enantioselective Total Syntheses of the Piperidine Alkaloids (S)-Coniine and (2R,6R)-trans-Solenopsin A via Catalytic Asymmetric Imine Hydrosilylation

“…Endocyclic imines of the type required by our synthetic strategy have themselves been the subject of much synthetic effort. − Our attempt at direct synthesis of these compounds from 5-chlorovaleronitrile and organometallic reagents 10,13,14 did not afford the expected cyclic imines; however, ω-chloro ketones 4a and 4b which were instead obtained (Scheme ) served as useful synthetic intermediates . Transient preparation of ω-azido ketones via solid/liquid phase-transfer catalysis followed by aza-Wittig cyclization ,, afforded the desired imines.…”

“…The de of this compound was determined to be g99% by chiral GC analysis of the trifluoroacetamide derivative (prepared after removing the BOC group with TFA in CH 2Cl2): 1 H NMR (300 MHz, CDCl3) δ 3.93 (m, 1 H), 3.80 (m, 1 H); 1.46 (s, 9 H), 1.20-1.90 (m, 29 H). 0.88 (t, 3 H, J ) 6.2 Hz); 13 (2R,6R)-(-)-trans-2-Undecyl-6-methylpiperidine((2R,6R)--(-)-trans-Solenopsin A), 2. 25 The title compound was prepared by stirring carbamate 9 (28.1 mg, 0.08 mmol) with excess TFA (ca.…”

Modification of the anabaseine pyridine nucleus allows achieving binding and functional selectivity for the α3β4 nicotinic acetylcholine receptor subtype

“…The m-tolyl derivative 7 was prepared transforming 3-bromotoluene into the corresponding mtolylmagnesium bromide 26 [43], which was reacted with 5-bromovaleronitrile in a tandem addition-cyclization reaction at room temperature in tetrahydrofuran to give the desired compound [46]. Alternatively, 5-bromovaleronitrile was coupled and cyclized with organolithiums [47]. Indeed, compounds 8, 9, 11 and 14 were synthesized by reaction of 5bromovaleronitrile, respectively, with commercially available phenyllithium 27 or (3fluorophenyl)lithium 28, (3-bromophenyl)lithium 29 and (3-bromo-5-fluorophenyl)lithium 30, which were in turn prepared from precursor bromophenyl derivatives by treatment with 1.6 M n-butyllithium in hexane [48].…”

2,3,4,5-Tetrahydropyridine (Δ1-piperideine) and its derivatives. Synthesis and chemical properties

“…When studying cyclisation of 5-halo-substituted nitriles 79 induced by organolithium compounds on refluxing in benzene, Gallulo et al 89 found that with bromo-substituted nitriles 79 the reaction time is shorter and the yields of the piperideines 1 are higher than those attained with chloro-derivatives. In another study, 90 the piperideine 1 (R = Ph) was prepared in 37% yield in a similar way by refluxing 5-chloropentanenitrile and PhLi in an Et 2 O ± cyclohexane mixture.…”