An efficient route to chiral trans-2,5-dialkylpyrrolidines via stereoselective intramolecular amidomercuration

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

“…However, NOE measurements gave reasonable indications of the assigned stereochemistries, but were certainly not definitive, as was the case with the related tetrahydrofurans. 3 Definite structural proof was finally achieved by pertinent literature comparisons, especially of 1 H NMR data 43 and, in particular, by single crystal X-ray determinations of the cis-2,5-dialkyl-3-iodopyrrolidine 37f together with the isomeric 2-phenylpyrrolidines 36j and 37k. 44 Although many of the iodopyrrolidines were obtained as solids, these did not provide crystals suitable for X-ray analysis from the initial recrystallisations.…”

“…Iodopyrrolidine 37f (0.05 g, 0.12 mmol) was deiodinated under the conditions described in the general procedure to afford the title compound 50b (0.03 g, 81%) as a colourless, viscous oil: R f 0. (26), 125 (43), and 91 (23) [Found: M ϩ ϩ 1, 310.1836].…”

Enantiodivergent Synthesis of (+)‐ and (−)‐Pyrrolidine 197B: Synthesis of trans‐2,5‐Disubstituted Pyrrolidines by Intramolecular Hydroamination

“…In contrast, their syntheses required 16 steps starting from C 2 ‐symmetric diepoxides derived from d ‐mannitol . Concerning the synthesis of (+)‐pyrrolidine 197B, to the best of our knowledge, our approach with nine steps is at the same level as the best published syntheses, by Takahata, Ohkubo, and Momose (ten steps), Mandille et al. (eight steps), and Marks et al.…”

ELECTROPHILE MEDIATED HETEROATOM CYCLIZATIONS ONTO C-C Π-Bonds. PART 2: METAL ION MEDIATED CYCLIZATION

“…Cyclizatiodcarbon monoxide capture in methanol allowed for the conversion of a series of sulfonamides 63a-b into the corresponding five and six-membered heterocycles 64a-b in good yield with a high degree of stereoselectivity; in all cases trans-disubstituted products predominated (truns:cis 3: 1-50: l).31 Mercuric salts are particularly useful for the cyclization of unsaturated N-protected amides.12-44 A series of papers by Takahata and Momose demonstrates that cyclization of unsaturated carbamates with mercuric salts constitutes a versatile method for the synthesis of alkaloids and related compounds. [36][37][38][39][40][41][42][43][44] A conformationally restricted substance P antagonist 67 has been prepared from carbamate 65 by sequential treatment with mercuric trifluoroacetate and sodium borohydride which afforded the 2-azabicyclo Homochiral C, symmetric 2,5-fruns-disubstituted pyrrolidines are highly sought after ligands for use in asymmetric synthesis and mercury (11) induced cyclizations have proved particularly useful for their synthesis. Carbamate 68 (four steps from L-alanine) undergoes stereospecific cyclization with Hg(II)/NaBH4 to afford the C2 symmetric carbamate 69 in high yield;33 acid catalyzed deprotection affording the amine 70 as its highly crystalline hydrochloride salt (89%).…”