Michael addition radical cyclization

A Favorskii-type rearrangement occurs on boron trifluoride promoted lead tetraacetate oxidation of enamines274 (Scheme 119). Five-membered rings may also be constructed by a Michael addition-radical cyclization process275 (Scheme 120). 

Michael-type radical cyclization." A short synthesis of 3-demethoxyerythra-tidinone (3) involves a Michael-type radical addition. Thus 1 on reaction with BujSnH (AIBN) affords 2 as a single isomer in 65% yield. This product is converted by a three-step sequence into 3. 

Interesting intramolecular cyclization of 1-nitroalkyl radicals generated by one-electron oxidation of aci-nitro anions with CAN is reported. As shown in Eq. 5.44, stereoselective formation of 3,4-functionalized tetrahydrofurans is observed.62 l-Nitro-6-heptenyl radicals generated by one electron oxidation of aci-nitroanions with CAN afford 2,3,4-trisubstituted tetrahydropyrans.63 The requisite nitro compounds are prepared by the Michael addition of 3-buten-l-al to nitroalkenes. 

An intramolecular radical cyclization gives the cxo-cyclic compounds, which has been extensively used in the synthesis of cyclic compounds. Michael additions of allyl alcohols or propargy 1 alcohols to nitroalkenes and the subsequent treatment with tin radicals provide a useful method for the preparation of substituted furans (Eqs. 7.83 and 7.84).126... 

Some syntheses of decanones and octalones, angularly substituted by a CF3 group, have also been performed by means of radical cyclization or by intramolecular Michael addition. These precursors have allowed access to other steroid derivatives with a trifluoromethyl group in the 19 position (Figure 4.8). ... 

The l,3,3,3a,8a-tetrahydro-8-oxa-2-thia- 205, l,3,3,3a,8a-tetrahydro-2,8-dioxa- 206, and 3,3a,8,8a-tetrahydro-12/-2-thia-8-aza-cyclopenta[ ]indene-2,2-dioxide 207 were prepared by Michael addition or radical cyclization from the corresponding sulfones 202-204 and brominated-dehydrobrominated (in the case of 207, after tosylation) to produce 1,5-diheteropentalene systems 208-210, respectively <1997TL5315>. 

Radical cyclization of p-bromoalkynes.2 Addition of (C6H5)3SnH and AIBN to benzene solutions of a p-bromoalkyne and a Michael acceptor results in annelated cyclopentanes in moderate yield. 

Scheme 24 illustrates how this notation can be combined with that of Seebach.73 Clive has formed a new ring by sequencing a Michael reaction, a carbonyl addition, and a radical cyclization.79 Phenylsele-noacrylonitrile is the actual reagent that accomplishes the transformation implied by synthon (7). 

Michael addition of pentM-yn-1-thiol to an activated alkyne produces co-yne vinylsulfides 424 as a separable mixture of the E and Z isomers. On treatment with -Uu (SnI I and a radical initiator, these substrates undergo a double radical cyclization accompanied by [(-fragmentation of the stannyl radical. The process is regio-, chemo-, and stereo-selective and produces the -isomer of the 5-substituted 3,4-dihydm-2//-thiopyran (Scheme 134) <1997JOC8630>. 

Baylis-Hillman adducts such as 55 and 56 derived from 2-nitrobenzaldehydes were shown to function as useful precursors to functionalized (1H)-quinol-2-ones and quinolines. Treatment of 55 and 56 with iron and acetic acid at 110 °C afforded 57 and 58, respectively <02T3693>. A variety of other cyclization reactions utilized in the preparation of the quinoline scaffold were also reported. An iridium-catalyzed oxidative cyclization of 3-(2-aminophenyl)propanols afforded 1,2,3,4-tetrahydroquinolines <02OL2691>. The intramolecular cyclization of aryl radicals to prepare pyrrolo[3,2-c]quinolines was studied <02T1453>. Additionally, photocyclization reactions of /rans-o-aminocinnamoyl derivatives were reported to provide 2-quinolones and quinolines <02JHC61>. Enolizable quinone and mono- and diimide intermediates were shown to provide quinolines via a thermal 6jt-electrocyclization <02OL4265>. Quinoline derivatives were also prepared from nitrogen-tethered 2-methoxyphenols. The corresponding 2-methoxyphenols were subjected to a iodine(III)-mediated acetoxylation which was followed by an intramolecular Michael addition to afford the quinoline OAc O... 

Conjugate addition of /3-ketoesters or 1,3-diketones to ethyl propynoate leads to Michael adducts of type 8 which undergo radical cyclizations to furans in the presence of 2,2 -azobisisobutyronitrile (AIBN)/tributyltinhydride... 

It arises from 54 by cyclization and retro-Claisen loss of an ethoxycar-bonyl group. Brettle suggested that 54 was formed from radical disproportionation followed by Michael addition of the carbanion to the resulting ethyl methyleneacetoacetate. Alternatively, 52 could likewise be derived from a-carbonyl cation intermediates formed by one-electron oxidation of 51. 

For 83 with n = 3, reduction at —0.9 V gave little cyclization (20%) neither in DMF nor in microemulsions, indicating that the radical is not significantly undergoing 5-endo-cyclization [228]. At —1.5 V, where the anion is formed, the competition between Michael addition and protonation was different for reaction in DMF and in microemulsions, giving 19% cyclization in DMF and 62-70% in microemulsions, indicating that the anion is formed in a water-free part of the microemulsion. 

PyrroUdine-3-carboxylic esters. The selenoacrylic esters are obtained from adducts of PhSeCl and acrylic esters by base-promoted dehydrochlorination. After Michael addition of allylic amines to the selenoacrylates, radical generation via selenium abstraction starts the free radical cyclization. 

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