Radical ring closure

J E G E R Tetrahydrefuran synthesis Free radical ring closure of alcohols with F%> AcO)41<> tetrahydrofurans... 

In the case of p-methoxystyrene (p-MeOCgH4CH=CH2), the cation-radical ring closure can lead to 1,2-dianisylcyclobntane or 4-anisyl-6-methoxy-3,4-dihydronaphthalene. Thermodynamic simulations show that the former should be favored in the absence of a solvent, whereas the latter product could be stabilized by a polar solvent (O Neil and Wiest 2006). Of course, such a solvent has to be fairly polar and not nncleophilic. 

Alkylimidazolinm tetraflnoroborates are, for example, ionic liquids at room-temperature that can provide an anion to stabilize an intermediate cation-radical with no possibility of nucleophilic attack on it. Ionic liquids have a huge memory effect, and their total friction is greater than that of conventional polar solvents. Thus, the total friction of l-ethyl-3-methylimidazolium hexafluoro-phosphate is about 50 times greater than that of AN (Shim et al. 2007). The solvent effects of ionic liquids on ion-radical ring closures deserve a special investigation. The ring closure reactions can be, in principal, controlled by solvent effects. 

Reduced pyrimidines by radical ring-closure reactions... 

Several examples of the synthesis of cyclonucleoside derivatives by radical ring-closure reactions are also available <1996T9496, 1999J(P1)1257, 2000T8689, 2002CBC534, 2005EJ04640>. 

In contrast to the synthesis of bicyclic azetidinones containing a carboxyl group on the atom adjacent to the lactam nitrogen (see Section 5.12.3.4), few examples are reported in which bicyclic azetidinones without this carboxyl group are prepared from azetidinone precursors. One unique approach, however, utilized a free radical ring closure to obtain 6-oxa-l-azabicyclo[5.2.0]nonan-9-one (116) in modest yield (81TL2689). 

Formation of five-membered heterocycles through radical methodologies has been investigated extensively. Inter-, intramolecular, and cascade reactions have been reported for the synthesis of heterocycles. In the case of intramolecular cyclizations, 5-exo pathway is the preferred mode of reactivity. Rate constant for the formation of pyrrolidine by radical ring closure has been reported [95AJC2047],... 

For a detailed discussion of the rules for radical ring-closure, see A.L.J. Beckwith, C.J. Easton and A.K. Serelis, 1980, J. Chem. Soc., Chem. Commun., 482. For Baldwin s earlier rules for ring-closure, see J.E. Baldwin, 1976, J. Chem. Soc., Chem. Commun., 734. 

Bose and colleagues described the construction of tetracyclic isoquinolines and quinazolines via aryl radical cyclization (equation 72)510. Sometimes, the radical formed as a result of 5-exo cyclization can undergo further rearrangement as was discovered by Engman and coworkers, who report the preparation of antioxidant 2,3-dihydrobenzothiophenes (96, 97) by radical ring closure (Scheme 10)516. 

Rate constants for radical ring closure (s-1, 25 °C) (sp3 carbon-centered radicals)... 

The formation of a cyclohexyloxyl radical via 6-exo-trig manner is promoted by the rigid bicyclic structure derived from the sugar benzylidene group (eq. 3.57a). Moreover, eq. 3.57b indicates that radical ring closure to a formyl group is preferable to that onto an olefinic group. 

Radical ring closure of an sp3 carbon-centered radical to a hydrazone group in compounds (174) can be carried out via 5-exo-trig manner. The silicon connection (Si-tethered) is removed by oxidative treatment with H202 to generate 2-amino-1,3-diols (175) (eq. 3.66) [189-191]. 

This was not the case when alkynes were employed for 5-exo-dig cyclizations, nor when the radical ring closure required an energetically less favorable P-oriented anomeric radical. Low yields of the C-glycosides were characteristic for both instances as depicted in Figure 7. Whereas the cyclization rates could not readily be modified, it seemed more appropriate to diminish the rate of the competitive second electron transfer step by modifying the reducing power of Smij through the omission of the cosolvent, HMPA. Of course, this could... 

The azetidinone ring system 43 is an important structural feature of the powerful b-lactam famiUes of antibiotics and appears in many other natural products such as clavulanic acid. Free radical-based routes to this ring system are remarkable for their variety and range. Four distinct radical-based disconnections have been investigated for azetidinone preparation. Disconnection a impUes closure of a carbamoyl-type radical onto an imsaturated acceptor group. Disconnection b imphes a closure of an amidoalkyl (a-carbamoyl) radical onto an enamide acceptor. Disconnection c points to an amidyl radical ring closure onto an alkene acceptor. Finally, disconnection d connotes ring closure of an acyl radical onto an imine acceptor (Scheme 11). 

The finely tuned reactivity of tri-n-butyltin hydride and of the resulting tin radical allows it to mediate radical additions to alkenes and alkynes in reductive carbon-carbon bond formation and for radical ring closures . It is a highly versatile and efficient reagent, but not a very green one delivering one useful atom (hydrogen, MW = 1) for every 40 atoms (MW = 290) lost as waste. 

For a similar sequence involving a free radical ring closure, see Kraus GA, Thurston J (1987) Tetrahedron Lett 28 4011... 

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