Metal-Catalyzed 1,2-Shift of Diverse Migrating Groups in Allenyl Systems as a New Paradigm toward Densely Functionalized Heterocycles

Abstract

A general, mild, and efficient 1,2-migration/cycloisomerization methodology toward multisubstituted 3-thio-, seleno-, halo-, aryl-, and alkyl-furans and pyrroles, as well as fused heterocycles, valuable building blocks for synthetic chemistry, has been developed. Moreover, regiodivergent conditions have been identified for C-4 bromo- and thio-substituted allenones and alkynones for the assembly of regioisomeric 2-hetero substituted furans selectively. It was demonstrated that, depending on reaction conditions, ambident substrates can be selectively transformed into furan products, as well as undergo selective 6-exo-dig or Nazarov cyclizations. Our mechanistic investigations have revealed that the transformation proceeds via allenylcarbonyl or allenylimine intermediates followed by 1,2-group migration to the allenyl sp carbon during cycloisomerization. It was found that 1,2-migration of chalcogens and halogens predominantly proceeds via formation of irenium intermediates. Analogous intermediate can also be proposed for 1,2-aryl shift. Furthermore, it was shown that the cycloisomerization cascade can be catalyzed by Brønsted acids, albeit less efficiently, and commonly observed reactivity of Lewis acid catalysts cannot be attributed to the eventual formation of proton. Undoubtedly, thermally induced or Lewis acid-catalyzed transformations proceed via intramolecular Michael addition or activation of the enone moiety pathways, whereas certain carbophilic metals trigger carbenoid/oxonium type pathway. However, a facile cycloisomerization in the presence of cationic complexes, as well as observed migratory aptitude in the cycloisomerization of unsymmetrically disubstituted aryl- and alkylallenes, strongly supports electrophilic nature for this transformation. Full mechanistic details, as well as the scope of this transformation, are discussed.

Silver and Brønsted Acid Catalyzed Nazarov‐Type Cyclizations To Generate Benzofulvenes

“…[4] The allenic version of the 4p electrocyclization of arylprop-2-ene-1-yl cations by a Nazarov-type reaction, [5] that is, the transformation of arylbuta-2,3-dienyl cations, would provide a direct route to benzofulvenes (Scheme 1). [6] Early attempts to generate the latter from a-allenyl benzyl alcohols using stoichiometric HgBr 2 showed the feasibility of this approach, [7] although competitive allene activation toward nucleophilic attack of the alcohol functionality to give 2,5-dihydrofurans could not be avoided. [8] More recently, specific examples of a domino 4p electrocyclization/Friedel-Crafts reaction using stoichiometric TsOH at elevated temperatures were reported.…”

Efficient Synthesis of Chiral Trisubstituted 1,2‐Allenyl Ketones by Catalytic Asymmetric Conjugate Addition of Malonic Esters to Enynes

“…[17] Importantly,the family of 5a has been reported to possess antimicrobial, [18] anti-PDE 3 , [19] antiinflammatory, [20] antimalarial, [21] hypolipidemic, [22] and analgesic [23] activities (Scheme 2b). Additionally, 3ab could also be transformed to trisustituted furan 5b under treatment by AuCl 3 in 79 %y ield with 99 % ee, [24,25] which are important skeletons for many biologically active compounds and pharmacologicals (Scheme 2b).…”

Metal-catalyzed Furan Synthesis. A Review

“…Key to this work is the 1,2-migration of a variety of functional groups, namely sulfide, 66 selenide, 67 halide, 68 alkyl and aryl moieties. 69 Despite the apparent similarity of these processes they proceed via different mechanisms.…”