Mechanistic Aspects and Synthetic Applications of Radical Additions to Allenes

Abstract

More than 50 years have passed since Haszeldine reported the first addition of a trifluoromethyl radical to an allene; in the intervening years, both the chemistry of allenes and the reactivity of single-electron species have become topics of intense interest. In this Review, we provide an overview of the fundamentals of radical additions to allenes and highlight the emergence of theoretical and experimental evidence that reveals unique reactivity patterns for radical additions to allenes as compared with other unsaturated compounds. Factors capable of exerting control over the chemo-, regio-, and stereoselectivities of the attack of carbon-and heteroatom-based radicals at each of the three potential reactive sites in an allene substrate are described. These include reaction conditions, the nature of the attacking radical, the substitution pattern of the allene, and the length of the linker between the radical center and the proximal allene carbon in the substrate. Cycloaddition reactions between allenes and partners containing π-bonds, which are likely to proceed through radical pathways, are presented to highlight their ability to rapidly access complex polycyclic scaffolds. Finally, the synthetic utility of the products arising from these chemistries is described, including their applications to the construction of complex molecules.

A complementary approach to conjugated N-acyliminium formation through photoredox-catalyzed intermolecular radical addition to allenamides and allencarbamates

“…In principle, a new method for its generation could greatly enhance the value of the allenamide building block, as well as potentially unlocking new chemical reactivity yet unseen in the context of electrophilic activation. We envisaged that a route to the conjugated N -acyliminium intermediate could be achieved via an intermolecular addition of an electrophilic radical to an allenamide ( 1 ) followed by an oxidation process on the subsequently formed radical ( Scheme 3 ) [ 41 ]. The thought process behind this approach is based on three observations; (i) Akita and co-workers disclosure on the photoredox-catalyzed oxytrifluoromethylation of allenes 6 to give 2-trifluoromethylated allyl acetates 7 [ 42 – 44 ]; (ii) that intramolecular radical cyclization of allenamides have been reported by Hsung and co-workers, where the radical adds principally to the central carbon of the allene ( 10 ) [ 45 ]; and (iii) the photoredox-catalyzed addition of radicals to enamides reported by Masson [ 46 – 49 ], and more recently by our own laboratory in the synthesis of N , N’ -aminals [ 50 ].…”

Palladium-catalyzed allene synthesis enabled by β-hydrogen elimination from sp2-carbon

“…14 The active nature imparted by its unique orthogonal cumulative π-system also makes them highly versatile and useful building blocks in organic synthesis. [15][16][17][18][19] Although numerous methods for the preparation of allenes have been developed, [20][21][22][23][24] they still lag far behind the growing demand in application. At present, the majority of the existing methodologies rely on the utilization of elaborate alkynes.…”

Polycyclic Compounds from Allenes via Palladium-Mediated Intramolecular Carbopalladation/Nucleophilic Substitution Cascade Processes

“…16,17 In the last few decades the chemistry of allenes has blossomed to such an extent that today's methodologies based on this class of molecules are very powerful synthetic tools. [18][19][20][21] Amongst the chemical transformations of allenes, transition-metal-promoted reactions are of particular interest. [22][23][24][25][26][27][28][29][30][31] Generally, transition-metal derivatives can react with allenes in two ways: As a Lewis acid they can coordinate either double bond, usually the less hindered one, and activate it for further transformations, or, upon coordination, carbometallation can occur creating a novel organometallic species that can undergo further transformations.…”