Domino radical

Scheme 3.1. General scheme for an intramolecular domino radical reaction.

Scheme 3.5. Rare example of a domino radical ring expansion/cationic cyclization procedure.

Scheme 3.7. Samarium(ll)iodide-induced domino radical cyclization/alkylation procedure...

Scheme 3.8. Domino radical cyclization procedure in the synthesis of lysergic acid derivatives.

Scheme 3.11. Domino radical cyclization process towards the total synthesis of CP-263,114 (3-32).

Another domino radical cyclization approach, which allows construction of the B- and E-rings of the alkaloid ( )-aspidospermidine (3-46), has been described by the same group [25]. Transformation of the iodoazide 3-44 into the tetracycle 3-45 was accomplished in 40 % yield by selective attack at the carbon-iodine bond in the... 

Scheme 3.12. Domino radical cyclization towards the synthesis of azadirachtin (3-38).

Scheme 3.15. Domino radical procedure in the synthesis of camptothecin (3-47) and analogs.

N-Aziridinylimines are valuable substrates for domino radical cydizations since they are able to serve simultaneously as radical acceptors and donors. They allow a versatile and general construction of quaternary carbon centers from carbonyl compounds [33]. By employing this methodology, an elegant and stereoselective synthesis of ( )-modhephene (3-70), one of the rare naturally occurring [3.3.3]propellanes,... 

Scheme 3.16. Domino radical cyclization in the total synthesis of (+)-podophyllotoxin (3-59).

During the course of a short and efficient total synthesis of (-) -dendrobine (3-76), an alkaloid which exhibits antipyretic and hypotensive activities [37], a new domino radical sequence has been exploited by Cassayre and Zard which involves the cycli-... 

Scheme 3.21. Domino radical macro-cyclization/transannular-cyclization procedure for the synthesis of the taxane skeleton.

Scheme 3.22. Domino radical cyclization procedure for the synthesis of [6.5.5] fused tricycle 3-87.

Scheme 3.25. Dioxatriquinanes by triethylborane-induced domino radical atom transfer/ cyclization of 1,5-diynes.

Scheme 3.26. Synthesis of pyrrozidine 3-105 by a domino radical cyclization via an aminyl radical.

Scheme 3.27. General scheme of domino radical ring expansion/cyclization procedure.

An early - but mechanistically interesting - construction of a bicyclo[3.1.0]oxa-hexane by a domino radical cyclization was presented by Luh s group [50]. The addition of tributyl tin and AIBN to a solution of bromides 3-111 in refluxing benzene gave 3-114 as single diastereoisomers in acceptable yields via the intermediates 3-112 and 3-113 (Scheme 3.29). It is important that the cyclopropyl carbinyl radical intermediate has the correct stability and reactivity, which is achieved by the a-silyl substituent. 

Another Lewis acid-catalyzed atom-transfer domino radical cyclization, to produce various bicyclic and tricyclic ring skeletons, has been developed by Yang and coworkers [54]. Reactions of the a-bromo-(3-keto ester 3-125 with Yb(OTf)3 and Et3B/02 led to the bicycle 3-126 in 85 % yield (Scheme 3.33). The reaction proceeds via a (>-endo-Irig and 5-exo-trig cyclization after initial abstraction of the bromine... 

Scheme 3.34. Intermolecular domino radical addition procedure for the synthesis of silyl-protected allylic alcohols.

Scheme 3.35. Domino radical cyclization/p-elimination process involving enantiopure sulfoxides.

Scheme 3.36. Enantioselective intermolecular domino radical addition procedure.

A rather new concept in the context of domino radical cydizations has been developed by Gansauer and coworkers utilizing titanocene-complexes for the radical opening of unsaturated epoxides. The titanocene-catalyzed reactions [61] of 3-145 primarily led to radical 3-146, which underwent a subsequent intermolecular addition to a present a,(3-unsaturated carbonyl compound to form bicyclic carbocy-cles of type 3-148 via the intermediate 3-147 after aqueous work-up (Scheme 3.38) [62]. From a kinetic point of view, the reaction is remarkable since the intermolecular addition of simple radicals to a,(3-unsaturated carbonyl compounds is not an easy task, as highlighted above. 

Scheme 3.37. Domino radical addition/cyclization-reaction for the asymmetric synthesis of (3-aminobutyrolactones.

Scheme 3.45. Domino radical ring-opening/cyclization procedure for the synthesis of spiroketone 3-171.

Scheme 3.48. Thermolysis of benzoenynes-allenes initiating a domino radical cyclization.

Scheme 3.50. Domino radical cydization strategies from linear acylic precursors (the formed bonds are highlighted in bold).

Scheme 3.54. Domino radical sequence in the synthesis of camptothecin analogues.

Scheme 3.57. Domino radical reaction in the synthesis of benzothienoquinoline derivatives.

Scheme 3.59. Sevenfold domino radical 6-endo-trig cyclization.

Scheme 3.62. Domino radical hydrogen abstraction-cyclization procedure in the synthesis towards Aspidosperma alkaloids.

Scheme 3.67. Alternative domino radical procedure for the construction of a [5.6.5] tricycle...

Clive and coworkers have developed a new domino radical cyclization, by making use of a silicon radical as an intermediate to prepare silicon-containing bicyclic or polycyclic compounds such as 3-271 and 3-272 (Scheme 3.69) [109], After formation of the first radical 3-267 from 3-266, a 5-exo-dig cyclization takes place followed by an intramolecular 1,5-transfer of hydrogen from silicon to carbon, providing a silicon-centered radical 3-269 via 3-268. Once formed, this has the option to undergo another cyclization to afford the radical 3-270, which can yield a stable product either by a reductive interception with the present organotin hydride species to obtain compounds of type 3-271. On the other hand, when the terminal alkyne carries a trimethylstannyl group, expulsion of a trimethylstannyl radical takes place to afford vinyl silanes such as 3-272. 

Scheme 3.71. Domino radical sequence of N-alkenylaziridinylmethyl radicals.

Scheme 3.77. Domino radical cyclization for the synthesis of fenestranes.

Scheme 3.78. Domino radical double ring expansion/cyclization process with oxime ethers.

---