Synthesis of Pyrrolidines by a Csp³‐Csp³/Csp³‐N Transition‐Metal‐Free Domino Reaction of Boronic Acids with γ‐Azido‐N‐Tosylhydrazones

Abstract

The reaction between g-azido-N-tosylhydrazones and boronic acids leads to the obtention of 2,2-disubstituted pyrrolidines in adomino process that includes 1) diazoalkane formation, 2) intermolecular carboborylation of the diazocompound, and 3) intramolecular carborylation of the azide, and comprises the formation of aC sp 3 À Csp 3 and aC sp 3 À N bonds on the same carbon atom. The reaction proceeds without the need of any transition-metal catalyst under microwave activation and features wide scope in both reaction partners.It can be applied to both alkyla nd arylboronic acids with equal efficiency.W ith N-tosylhydrazones derived from 2-(2-azidoethyl)-cyclopentanone and cyclohexanone the reactions are highly diastereoselective leading to the cis-fused bicyclic systems as unique diastereoisomers.T he scope of the process is illustrated by over sixty examples,including scaffolds present in natural alkaloids,and the mechanistic proposal is suppported by DFT-based computations.

Saturated Boronic Acids, Boronates, and Trifluoroborates: An Update on Their Synthetic and Medicinal Chemistry

“…In this case, intermediate boronic acids 127 underwent diastereoselective cyclization to give mono-, bi-, and tricyclic alkaloid-like structures 128. [119] 3.9. C(sp 3 )-heteroatom bond formation: Copper-free methods Conversion of saturated boronic derivatives into the corresponding alcohols by oxidation has been known (and widely used) for more than a half of century since its discovery by Brown's group in late 1950s.…”

Recent Updates on Azido‐reductive Cyclization Approaches: Syntheses of aza‐Heterocyclic Frameworks

“…Additionally, such bicyclic systems can be employed to synthesize natural alkaloids such as erythrinanes, homoerythrinanes, lepadiformines and cylindricines. [27] Vinyl azide is an excellent building block and explored in the iminyl-radical triggered cascade CÀ C bond cleavage/radical addition/cyclization to construct 3,4-dihydro-2H-pyrroles (Scheme 6). [28] The reaction of oxime esters 15 with vinyl azides 16 in the presence of a Ni-catalyst in basic medium rapidly furnished the cyanoalkylated pyrroles 17 with a wide range of functionalized substrates.…”

“…Noticeably, these reactions were less sensitive to the electronic nature of aryl boronic acids. Additionally, such bicyclic systems can be employed to synthesize natural alkaloids such as erythrinanes, homoerythrinanes, lepadiformines and cylindricines [27] …”

Construction of NH‐Unprotected Spiropyrrolidines and Spiroisoindolines by [4+1] Cyclizations of γ‐Azidoboronic Acids with Cyclic N‐Sulfonylhydrazones

“…Thepyrrolidine synthesis through the [4+ +1] approach can be also applied to acyclic N-tosylhydrazones as demonstrated in some representative examples presented in Scheme 4. The reaction leads to pyrrolidines and isoindolines featuring 2,2dialkyl (42,(44)(45)(46)a sw ell as 2-alkyl-2-aryl substitution (38)(39)(40)(41)43). Thep resence of as ensitive carboxylic ester (43)i s tolerated, and moreover,a na zide functionality,w hich is not in the proper position to undergo the cyclization also remains untouched in the reaction (42).…”