A stereochemically flexible approach to pyrrolidines based on 5-endo-trig iodocyclisations of homoallylic sulfonamides

Electrophilic Bromination of N‐Acylated Cyclohex‐3‐en‐1‐amines: Synthesis of 7‐Azanorbornanes

“…The chemical shift for the C(1) d of 18, 21, 22, and 23 (73.8 ± 74.5 ppm) evidences the dihydrooxazine and not the azetidine structure. These d values are similar to those for C(6) of 2-(trifluoromethyl)-(78.6 and 75.7 ppm [64]), 2-methyl-(72.26 ppm [62]), and 2-phenyl-4,5-dihydro-6H- [1,3]oxazines (74.2 ppm [65]). The chemical-shift values for the C(5) and C(8) ds of the bromo-1,3-oxazines 18, 22, and 23 are similar to each other (46.7 ± 51.3 ppm) and were not assigned separately.…”

Carbenium ion trapping using sulfonamides: an acid-catalysed synthesis of pyrrolidines by intramolecular hydroamination

“…), CH 2 Cl 2 , 20 C, 16 h. data of the corresponding iodocyclisation products and their deiodo derivatives. 7 As can be seen from Table 2, the key to inducing isomerisation towards what must be the more thermodynamically stable isomers is an increase in the amount of acid used rather than an increase in the reaction time. In the case of the glycine derivative 12a, the thermodynamically more stable isomer has the 2,5-cis-stereochemistry, 'cis'-13a, in which the two substituents adopt pseudoequatorial positions and is formed almost exclusively when an excess of acid is used, according to 1 H NMR analysis.…”

“…Firstly, we found that overall 5-endo-trig iodocyclisations of homoallylic sulfonamides 1, which give very largely the 2,5-transiodopyrrolidines 2 under basic conditions (Scheme 1), gave only the corresponding 2,5-cis diastereomers 3 if the base was omitted. 7 By starting with a single enantiomer of the precursor [1; R 1 ¼Et; R 2 ¼Bu], we were able to establish that formation of the latter most likely occurs by cycloreversion of the initially formed and hence kinetic isomers 2 back to precursor 1 and subsequent cyclisation to NHTs N Ts eventually produce only the thermodynamically more stable 2,5-cis-isomers 3. Presumably, the trigger for this is protonation of the trans-pyrrolidines at nitrogen by the hydrogen iodide formed as the cyclisation proceeds and which is now not removed as no base is present.…”

“…These are, of course, the very familiar halo-or selenocyclisations processes for ring closure, which can operate in a number of modes, including 5-and 6-exo as well as 5-endo examples. 5 During our studies of such cyclisations, 6,7 we were stimulated to search for alternatives to both molecular iodine and selanyl halides for a number of reasons, not the least of which were the fact that a relatively large excess (3 equiv) of iodine is required and general limitations for scale up in both cases, especially when using the selenium-based reagents, where cost and disposal become limiting considerations. The idea to attempt to form pyrrolidines and perhaps N-heterocycles with other ring sizes using such chemistry but with alternative activating agents for the alkene arose from two observations.…”

Synthesis of 3-Iodomethyl Sultams

“…26,27 Intramolecular haloamination of unsaturated sulfamide derivatives (Scheme 1, A), which opens the way to halo-substituted pyrrolidine and piperidine derivatives is currently well investigated. In this case, elemental iodine is most commonly used as the halogenating agent in the presence of NaHCO 3 or K 2 CO 3 , 28,29 N-bromosuccinimide (NBS) 30 or N-iodosuccinimide (NIS). 31 Another approach involves the use of an oxidant and a halogen source: (diacetoxyiodo)benzene PhI(OAc) 2 (PIDA)/KI, 32,33 HF/Py, 34 Oxone ® (potassium monopersulfate)/RI 35 or KBr, 36 tBuOCl/NaI, 37 chloramine-T (CT)/I 2 , 38,39 and Cu(OTf) 2 /iPrI.…”