Radical chemistry natural product synthesis

Birch reduction of aromatic ethers is well known to afford alicyclic compounds such as cyclohexadienes and cyclohexenones, from which a number of natural products have been synthesized. Oxidation of phenols also affords alicyclic cyclohexadienones and masked quinones in addition to C—C and/or C—O coupled products. All of them are regarded as promising synthetic intermediates for a variety of bioactive compounds including natural products. However, in contrast to Birch reduction, systematic reviews on phenolic oxidation have not hitherto appeared from the viewpoint of synthetic organic chemistry, particularly natural products synthesis. In the case of phenolic oxidation, difficulties involving radical polymerization should be overcome. This chapter demonstrates that phenolic oxidation is satisfactorily used as a key step for the synthesis of bioactive compounds and their building blocks. 

Since an amino group is one of the most important functional groups in organic chemistry and is found in many natural products, the radical reactions using C=N bonds as radical traps have attracted a great deal of recent attention among organic chemists and have proved to be of synthetic importance in natural product synthesis... 

The field of natural products synthesis has been particularly fruitful in showing the flexibility and power of radical chemistry several examples from the literature have been collected and commented on in some books and reviews , therefore in the present chapter we describe only a few examples. 

In recent years, radical aryl migrations have received increased attention within the synthetic organic chemistry community. Yet, these reactions are also found as key steps in complex natural product synthesis [78]. For example, the neophyl rearrangement-which is the 1,2-phenyl migration of the neophyl radical 42 to form the tertiary radical 44 (probably via spirocyclohexadienyl radical 43)-was discovered by Urry and Kharasch more than 60 years ago (Scheme 13.9) [79], since which time numerous reports on neophyl-type rearrangements have been presented [80]. However, despite these efforts the postulated intermediate 43 has not yet been identified [81], The slow neophyl rearrangement (k = 762 s at 25 °C, [82]) can be used as a radical clock [83], The 1,2-aryl migration can also occur from C- to... 

Negishi E, Tan Z (2005) Diastereoselective, Enantioselective, and Regioselective Carbo-alumination Reactions Catalyzed by Zirconocene Derivatives. 8 139-176 Netherton M, Fu GC (2005)Palladium-catalyzed Cross-Coupling Reactions of Unactivated Alkyl Electrophiles with Organometallic Compounds. 14 85-108 NicolaouKC, KingNP, He Y (1998) Ring-Closing Metathesis in the Synthesis of EpothUones and Polyether Natural Products. 1 73-104 Nishiyama H (2004) Cyclopropanation with Ruthenium Catalysts. 11 81-92 Noels A, Demonceau A, Delaude L (2004) Ruthenium Promoted Catalysed Radical Processes toward Fine Chemistry. 11 155-171... 

Abstract In this chapter different types of domino-processes are described which consist of the combination of cationic, anionic, radical, pericyclic and transition metal-catalyzed as well other reactions. The methodology is used for the highly effective synthesis of carbocycles and heterocycles as well as of natural products and other interesting materials. It is also employed as an efficient tool in combinatorial chemistry. 

Thus, radical addition reactions provide a useful means of functionalising pyridines, quinolines and isoquinolines, particularly when it is reasonable to employ the heteroaromatic base in excess. Intramolecular variants of the reaction are devoid of that limitation and have been widely exploited in the synthesis of nitrogen-containing heteroaromatics. The mildness of the reaction conditions have found favour in natural products total synthesis and medicinal chemistry programs. These bare testament to the reactions worth and have raised its stature from academic curiosity to useful synthetic tool. 

Intramolecular radical cyclizations are exceptionally useful and have found widespread use in organic synthesis [11,12]. Kolbe chemistry has been exploited in this manner providing access to the prostaglandin precursor 8 [13], and to ring systems (10) that are common to the angularly fused triquinane natural products [14]. 

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