Group Transfer Radical Cyclization Research Articles

Enantiospecific Synthesis and Cytotoxicity Evaluation of Ligudentatol: A Programmed Aromatization Approach to the 2,3,4‐Trisubstituted Phenolic Motif via Visible‐Light‐Mediated Group Transfer Radical Cyclization

A facile enantiospecific approach to (+)-ligudentatol (1) and (-)-ligudentatol (ent-1) is reported. The approach features the construction of a trisubstituted phenolic motif fused to a chiral aliphatic ring by a sequence of visible-light-mediated radical seleno transfer cyclization, bromination, concomitant selenoxide elimination-dehydrobromination, and demethoxycarbonylation, namely, a programmed aromatization. Biological evaluation of the enantiomers of ligudentatol obtained by the present route revealed for the first time their cytotoxicity towards various cancer cell lines.

ChemInform Abstract: Selective Approach Toward Multifunctionalized Lactams by Lewis Acid Promoted PhSe Group Transfer Radical Cyclization.

AbstractIrradiation of amido selenides in the presence of Yb(O‐Tf)3 allows an efficient, regiospecific, and stereoselective access to γ‐ and δ‐lactams.

Selective Approach toward Multifunctionalized Lactams by Lewis Acid Promoted PhSe Group Transfer Radical Cyclization

We have developed a regiospecific and highly stereoselective strategy for constructing the five-/six-membered monocyclic and bicyclic nitrogen heterocycle skeletons using PhSe group transfer radical cyclization of alpha-phenylseleno amido esters promoted by a Lewis acid (e.g., Yb(OTf)(3)) under UV irradiation. We obtained 5-/6-exo-trig mode cyclization products for the N-allyl/homoallyl substrates, whereas the enamide substrate gave 5-endo-trig ring closure.

Synthesis of γ-Butyrolactams by Photoinduced PhSe Group Transfer Radical Cyclization and Formal Synthesis of (±)-Isocynometrine with Diphenyldiselenide as Promoter

We have developed a strategy for constructing nitrogen heterocycles by photoinduced PhSe group transfer radical cyclization. trans-Alpha,beta-disubstituted gamma-butyrolactams (2-pyrrolidinones) were prepared in good yields (38-73%) with high regioselectivity and stereoselectivity from N-alkenyl alpha-PhSe beta-keto amides. Reaction outcomes were modulated by the steric effect of the substituents on the nitrogen atom of the cyclization precursors and the stereoelectronic effect of the substrates. Diphenyldiselenide, as an additive, was found to promote ring closure. The advantage of this strategy in natural product synthesis is demonstrated by a formal synthesis of (+/-)-isocynometrine.

New applications of dithiocarbamates in organic synthesis

AbstractThe application of dithiocarbamates in group transfer radical cyclization reactions is described. Carbamoyl diethyldithiocarbamates are synthesized in two high‐yielding steps from secondary amines and act as sources of carbamoyl radicals through chemical or photochemical initiation. Group transfer radical cyclization reactions lead to dithiocarbamate‐functionalized lactams. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:568–571, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20336

An Efficient and Highly Stereoselective Method to Synthesize 3-(1-Hydroxyalkyl)pyrrolidinone

Abstract Three contiguous stereocenters with syn–anti structure on the 3-(1-hydroxyalkyl)pyrrolidinone were constructed in one step with high yields and high diastereoselectivity by an Et2AlCl-catalyzed group transfer radical cyclization reaction from N-alkenyl-β-hydroxyalkanamides with 125-W UV lamp irradiation. The relative stereochemistry was confirmed by X-ray analysis.

Et2AlCl‐Promoted Asymmetric Phenylseleno Group Transfer Radical Cyclization Reactions of Unsaturated β‐Hydroxy Esters.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Et2AlCl-Promoted Asymmetric Phenylseleno Group Transfer Radical Cyclization Reactions of Unsaturated β-Hydroxy Esters

We have developed a new method for asymmetric phenylseleno group transfer radical cyclization of unsaturated beta-hydroxy esters. Various unsaturated alpha-phenylseleno beta-hydroxy esters underwent radical cyclization in the presence of Et(2)AlCl in benzene with sunlamp irradiation at 25-30 degrees C to give mono- and bicyclic group-transferred products in an efficient and highly regioselective and diastereoselective manner. To rationalize the high diastereoselectivities observed in this reaction, we propose a model based on chelation control of the aluminum alkoxides that are formed in situ. We devised a general method to prepare chiral radical precursors from which we obtained highly optically pure mono- and bicyclic group transfer products. The synthetic advantages of this method are demonstrated by our formal total synthesis of (-)-wilforonide. This paper presents the first examples of stereoselective group transfer radical cyclizations that occur via 1,2-asymmetric induction.

Xanthate Transfer Cyclization of Glycolic Acid-Derived Radicals. Synthesis of Five- to Eight-Membered Ring Ethers

A novel method for the preparation of functionalized five- to eight-membered ring ethers is described. This method involves the xanthate transfer radical cyclization of 2-(alken-l-oxy)-2-[(ethoxythiocarbonyl)sulfanyl]acetic acid methyl esters 6 to give good yields of xanthate-substituted five- to eight-membered ethers 7 and/or 8, depending on the length of the carbon chain. These cyclic ethers are usually obtained as mixtures of diastereomers. The cyclizations are performed at 150-160 C in tert-butylbenzene with di-tert-butyl peroxide as the initiator. This group-transfer radical cyclization was successfully applied in a total synthesis of lauthisan (44). The use of benzoyl xanthate (56) as a catalyst allows a visible light-induced xanthate transfer cyclization to a tetrahydrofuran in high yield.