Radical tandem

In the course of the 1990s, Yasui et al. [41b, 68] showed that, depending on the ligands attached to the phosphorus atom, phosphoranyl radicals may decay via three main processes a-scission, -scission and SET (Scheme 31). For example, in the presence of 10-methylacridinium iodide, phosphoranyl radicals generated from phenyl diphenylphosphinite decayed mainly via a-scission (Scheme 32) whereas phosphoranyl radicals generated from /so-propyl diphenylphosphinite decayed only via a SET process (Scheme 33). The reactivity of the phosphoni-umyl/phosphoranyl radical tandem has already been discussed in Sect. 3. 

Keywords Catalysis Cyclizations Electron transfer Radicals Tandem reactions... 

Scheme 12.20. Titanocene-catalyzed radical tandem reactions.

Thus, our radical tandem reactions offer highly stereoselective access to tri- and tetrasubstituted alkenes that are otherwise difficult to prepare. 

Scheme 15 Radical tandem sequence for tetrahydrofuran formation...

A radical tandem cyclization, consisting of two radical carbocyclizations and a heterocoupling reaction, has been achieved by electrolysis of unsaturated carboxylic acids with different coacids. This provides a short synthetic sequence to tricyclic products, for example, triquinanes, starting from carboxylic acids which are accessible in few steps (Scheme 6) [123]. The selectivity for the formation of the tricyclic, bi-cyclic, and monocyclic product depending on the current density could be predicted by applying a mathematical simulation based on the proposed mechanism. 

Scheme 6 Radical tandem cyclization to tricyclic compounds.

With type iii-e reactions compounds (71) are formed. A radical tandem reaction initiated by the Kolbe electrolysis of (88) gave tricyclic compounds (89) in a one pot reaction (Scheme 32) [111]. The electrochemical decarboxylation avoids the usually applied toxic tin hydride as reagent and... 

Scheme 32 Radical tandem cyclization initiated by Kolbe electrolysis.

Unsaturated carboxylic acids can be de-carboxylated to alkyl radicals that undergo an intramolecular addition. The S-exo-trig-cyclization of fi-allyloxy radicals, generated from an appropriate carboxylic acid, combined with a final heterocoupling has been applied to synthesize a precursor of prostaglandine PGF2q (Fig. 47) [246] and a branched carbohydrate (ratio of diastereo-mers 1.8 1) (Fig. 48) [247]. A radical tandem cyclization of a doubly unsaturated monocyclic carbocyclic acid provides a... 

Matzeit A, Schafer HJ (1995) Radical tandem cyclizations. In Torii S (ed) Novel trends in electroorganic synthesis, Kodansha, Tokyo... 

The group of activated olefins, which has so far probably received most attention in radical cyclizations, are enamides. Syntheses of various natural products, especially alkaloids, have been successfully completed using this strategy. Cyclizations onto enamides of the 6-endo type led to erysotrine [76] and lycorine alkaloids [77-79]. The skeleton of hydroapoerysopines [80] was successfully constructed by a 1-endo cyclization. Two new examples of radical tandem reactions, which commence with a 1-endo type cyclization, have appeared in recent literature. Construction of the cephalotaxine core structure 29 was achieved from enamide 30 in only one step (Scheme 11) [81]. 

The ketenethioacetal (277), prepared from the aldehyde (275) and 2-lithio-2-trimethylsilyl-l,3-dithiane (276), upon treatment with tributyltin hydride gave, via a radical tandem cyclization, the 2-(3-thiol-l-propyl)thieno[3,2-b]thiophene (278) (Scheme 19) <93TL5653>. 

Abstract Radical tandem reactions—and in a wider context radical dominos or cascades—have attracted a lot of attention because of their intrinsic elegance and the construction of a hroad and sometimes unique array of molecular architectiu es they allow in a single step. This review focuses on the latest progress in the design and development of new tandem reactions. The first part is devoted to intramolecular processes the second part covers tandem and domino processes involving both intra- and intermolecular steps. The third part introduces intermolecular-only reactions. Finally, the last part focuses on tandem reactions involving both radical and non-radical elementary steps. 

Radical tandem reactions and in a wider context radical dominos or cascades have attracted a lot of attention because of their intrinsic elegance and the construction of a broad and sometimes unique array of molecular architectures they allow. Contrary to a long-standing idea, efficiency and selectivity requirements can also be met. A good illustration is the one-pot assembly of hnear triquinane 2 from acychc precursor 1 (Scheme 1) [1]. In this ten-elementary radical step process, five C - C bonds are created as well as three quaternary centers and four stereogenic centers, almost all completely controlled. 

Den s et al. reported an interesting example of a radical tandem 1,4-addition/carbocyclization reaction initiated by oxidation of dialkylzinc by dissolved oxygen in the solvent [213]. Reduction of the final radical with dialkylzinc through a radical/polar crossover reaction afforded a new organo-zinc derivative that could be further fimctionahzed. 

Scheme 10 Formation of tetrahydrofmans by a novel radical tandem cyclization [66,67]...

A radical tandem cyclization, consisting of two radical additions and a heterocoupling reaction, has been achieved by coelectrolysis of unsaturated carboxylic acids with different coacids. This provides a short synthetic sequence to tricyclic products, such as... 

Titanocene-Catalyzed 5-exo Cydizations 443 Titanocene-Catalyzed Radical Tandem Reactions 444 Catalytic Enantioselective Epoxide Opening 445 Conclusion 448 References 449... 

Tandem oxidative cyclization of a-chloromalonate ester with Mn(OAc)3 and Cu(OAc)2 in EtOH at reflux affords 65% of lactone 124, analogously to the conversion of 35 to 36 and 37 [60]. Further elaboration yields estafiatin (125) (Scheme 39). Oxidation of 126 with Mn(OAc)3 and Cu(OAc)2 in AcOH at 50 °C results in hydrolysis to the ene dione, which is oxidized to the a-keto radical. Tandem cyclization and oxidation of the cyclopentanemethyl radical by Cu(II) affords 70-80% of 127, which was converted to tricycloillincinone (128) (Scheme 40) [61]. Oxidative cyclization of phenylmenthyl y -keto ester 129 with Mn(OAc)3 and Yb(OTf)3 in trifluoroethanol at -5°C provides 77% of 130 as a 38 1 mixture of diastereomers. 

In all these cases, we dealt with precursors bearing a ring, which generally serves as a template or as a radical acceptor. Many excellent reviews and book chapters have covered radical tandem reactions [5]. Herein, we will focus on two distinct approaches to radical cascades. The chapter will be devoted to the construction of polycyclic structures (at least 3 rings). We will deal with two distinct approaches the first one focussing on the use of acyelic precursors, the second one based on transannular processes. 

Among the very few reported possibilities offered by transannular cycle contraction of cyclododecenyl radicals to construct 9,5-, 8,6- or 7,7-bicyclic systems, the radical tandem approach to the taxanes planned by Pattenden, from the substituted A-ring precursor 134, introduces a new conceptual strategy, described as E in Scheme 29. First, a 12-e Jo-dig macrocyclization involving alkyl radical 135 occurs easily on the triple bond of the ynone moiety. The produced vinyl radical (major conformer is presented) 136 cyclizes in a 6- n-endo)-exol - n-exo)-endo transannular manner to assemble the unusual tricyclo[9.3.1.0 ]pentadecane framework 137 as a 6 1 ratio of diastereomers (Scheme 38) [55]. 

Other attempts to promote radical DA reactions were pursued, notably to open an entry into steroidal structures. An interesting case is the radical cyclization of ynone 153 in order to prepare tetracyclic ketone 155 through a 13-e rfo-dig macrocyclization-radical tandem transannular DA cascade. The unique resulting tetracyclic compound 158, displays a completely different structure with two contiguous quaternary sp carbons and two conjugated enone moieties (Scheme 42),... 

Guindon Y, Yoakim C, Gorys V, Oglivie WW, Delorme D, Renaud J, Robinson G, Lavallee J-F, Slassi A, Jung G, Rancourt J, Durkin K, Liotta D (1994) Stereoselective hydrogen transfer reactions involving acyclic radicals. Tandem substituted tetrahydrofuran formation... 

Marinkovic S, Hoffmann N Diastereoselective radical tandem addition-cycliza-tion reactions of aromatic tertiary amines by semiconductor-sensitized photochemical electron transfer. Eur J Org Chem 2004, (14) 3102-3107. 

---