Radical reactions alkynylations

Cobaloxime(I), electrochemically regenerated from chloro(pyridine)-cobaloxime (III) (232), has been employed as a mediator in the reductive cleavage of the C—Br bond of 2-bromoalkyl 2-alkynyl ethers (253), giving (254) through radical trapping ofthe internal olefin (Scheme 95) [390]. An interesting feature of the radical cyclization (253) (254) is the reaction in methanol, unlike the trialkyltin hydride-promoted radical reactions that need an aprotic nonpolar solvent. An improved procedure for the electroreductive radical cyclization of (253) has been attained by the combined use of cobaloxime(III) (232) and a zinc plate as a sacrificial anode in an undivided cell [391]. The procedure is advantageous in terms of the turnover of the catalyst and the convenience of the operation. 

Primary alkyl halides can also be alkynylated by silver acetylides. Isabelle and coworkers reported the reaction of methyl iodide, ethyl iodide and <7rmethyl iodide with several silver acetylides to give disubstituted alkynes.116 The authors preferred a non-radical-mediated mechanism for this reaction, as neither methane nor ethane, expected byproducts of a radical reaction, were observed. 

An immediate consequence of the different ease with which Cjp. .-element bonds dissociate is that in radical substitution reactions, alkyl radicals are preferentially formed. Only in exceptional cases are vinyl or aryl radicals formed. Alkynyl radicals do not appear at all in radical substitution reactions. In the following we therefore limit ourselves to a discussion of substitution reactions that take place via radicals of the general structure R1R2R3C-. 

The dual ability of carbonyl, alkenyl, and alkynyl groups to act as radical precursors as well as radical acceptors is of great importance for synthetic applications, since it would diversify the formation of carbon-carbon bonds by radical reactions. Each functional group has unique characteristics, which permit the generation of radicals from multiple bonds or the addition of radicals to multiple bonds in a selective manner. 

Another approach to carrying out tin-free radical fragmentation processes, developed by Fuchs, utilizes trifluoromethyl sulfone, or triflone, derivatives. Fuchs first reported examples of free radical alkynylation reactions using acetylenic triflone 102 [62]. What is most remarkable about these reactions is that the radicals being alkynylated are formed from the cleavage of C-H bonds standard radical precursors are not required. For example, when tetrahydrofuran is mixed with triflone 102 at room temperature, alkynylation occurs a to the ether oxygen in 92% yield (Scheme 21). In this case, the radical chain process is most likely initiated by traces of peroxides in the THF. Similarly, unactivated alkanes such as cyclohexane will react with triflone 102 in good yield (83% for cyclohexane) when heated with a catalytic amount of AIBN. 

Benati L, Calestani G, Leardini R, Minozzi M, Naimi D, Spagnolo P, Strazzari S, Zanardi G (2003) Cascade radical reactions via a-(arylsulfanyl)imidoyl radicals competitive [4-1-2] and [4+1] radical annulations of alkynyl isothiocyanates with aryl radicals. J Org Chem 68 3454-3464... 

The oxidative addition step in this reaction is postulated to involve singleelectron transfer from a low-valent cobalt complex to the alkyl hahde with the intermediate generation of alkyl radicals. This procedure enables sequential radical cychzation-alkynylation reactions of 6-halo-1-hexene derivatives [102]. 

In a reaction closely related to the latter, pyranylidene derivatives are obtained by the intermolecular radical coupling of alkynyl- or alkenylcarbene complexes and epoxides. Good diastereoselectivities are observed when cyclic epoxides are used. Moreover, the best results are reached by the generation of the alkyl radical using titanocene monochloride dimer [90] (Scheme 43). 

At present, the chemisty of selenophenes and tellurophenes is a relatively scantily studied area. Nevertheless, a number of new valuable contributions dealing with their chemistry have emerged. Electrophilic cyclization of l-(l-alkynyl)-2-(methylseleno)arenes provides a route to a variety of 2,3-disubstituted benzo[fe]selenophenes, as illustrated by the preparation of the system 88. Other useful electrophiles for similar reactions are E or NBS <06JOC2307>. Similar chemistry has also been employed in preparation of 2,3-disubstituted benzo[f>]selenophenes on solid phase <06JCC163>. In addition, syntheses of 2,3-dihydroselenolo[2,3- >]pyridines have been achieved using radical chemistry <06OBC466>. 

Reaction of dpp-bian with Mg in THF for 30 min reflux gives complex 87 (Ar = 2,6-diisopropylphenyl) which undergoes oxidative addition via m-bond metathesis with PhC=CH to give the black alkynyl amido complex 88. The insertion reaction of 88 with Ph2CO in EtzO yields complex 89. Unexpectedly, hydrogen abstraction to give the radical anion occurs simultaneously with ketone insertion.268... 

Cyclization of secondary alkyl radicals can occur with a, (S-alkynyl esters, such as 12, and proceeds with high stereoselectivity to give predominantly (Z)-exocyclic alkenes at low temperature upon reaction with (TMS)3SiH (Reaction 7.17) [28]. 

Support-bound triazenes, which can be prepared from resin-bound secondary aliphatic amines and aromatic diazonium salts [455], undergo cleavage upon treatment with acids, leading to regeneration of the aromatic diazonium salts. In cross-linked polystyrene, these decompose to yield nitrogen and, preferentially, radical-derived products. If the acidolysis of polystyrene-bound triazenes is conducted in the presence of hydrogen-atom donors (e.g. THF), unsubstituted arenes can be obtained (Entries 8 and 9, Table 3.47). In the presence of alkenes or alkynes and Pd(OAc)2, the initially formed diazonium salts undergo Heck reaction to yield vinylated or alkynylated arenes (Entry 10, Table 3.47). Similarly, unsubstituted arenes can be obtained by oxida-... 

The cyclization of secondary alkyl radicals with a, fi-alkynyl esters 18 proceeded with high stereoselectivity to give predominantly (Z)-exocyclic alkenes at low temperature upon reaction with (TMS SiH (equation 54)79. On the other hand, the formation of (E)-exocyclic alkenes predominated with Bu3SnH, the E/Z ratio being 98 2 at 80 °C. It has been suggested that the main factor controlling the formation of these products is the ability of (TMS Si and Bu3Sn radicals to isomerize the product alkene. That is,... 

The formation of rings with more than seven atoms has unfavorable rates because the addition step is often too slow to allow it to compete successfully with other pathways open to the radical intermediate. In stannane based chemistry for example, premature hydrogen abstraction from the organotin hydride is difficult to avoid. However, Baylis-Hillman adducts 111 derived from enantiopure 1-alkenyl (or alkynyl)-4-azetidinone-2-carbaldehydes are used for the stereoselective and divergent preparation of highly functionalized bicycles 112 and 113 fused to medium-sized heterocycles (Scheme 38) [80, 81]. The Baylis-Hillman reaction using nonracemic protected a-amino aldehydes has been attempted with limited success due to partial racemization of the chiral aldehyde by DABCO after... 

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