Alkynes carbon-centered radicals

Vinyl radical formation by intramolecular addition of a carbon-centered radical to an alkyne... 

ADDITIONS OF CARBON-CENTERED RADICALS TO ALKENES AND ALKYNES 735... 

One of the mildest general techniques to extend a carbon chain entails the addition of a carbon-centered radical to an alkene or alkyne. The method for conducting these addition reactions often determines the types of precursors and acceptors that can be used and the types of products that are formed. In the following section, synthetically useful radical additions are grouped into chain and non-chain reactions and then further subdivided by the method of reaction. Short, independent sections that follow treat the addition of carbon-centered radicals to other multiple bonds and aromatic rings and the additions of hete-roatom-centered radicals. 

Most of the recent synthetic developments in the field of radical cyclization have involved the reactions of carbon-centered radicals with alkenes and alkynes. Other useful acceptors include allenes,31 dienes30 and vinyl epoxides.32 The same methods are used for cyclizations to these acceptors as for radical additions, and the preceding chapter should be consulted for specific details on an individual method (the organization of this section parallels that of Section 4.1.6). Selection of a particular method to conduct a proposed cyclization is based on a variety of criteria, including the availability of the requisite pre-... 

Intramolecular addition of carbon-centered radicals to alkynes under reductive conditions has been examined by Dulcere and Rodriguez. Alkyl radical generation from 39 resulted in the formation of a substituted tetrahydrofuran 40, a nucleoside analog [95SL923]. An improved 5-exo-dig process for the formation of iodomethylene lactone has been reported [95T4665],... 

As a combined reaction of (3-cleavage of a cyclopropylcarbinyl radical and intermolecular addition, treatment of vinylcyclopropane (266) and activated alkyne in the presence of PhSSPh and AIBN forms a cyclopentene skeleton (267), through the initial addition of a thiyl radical to the vinyl group, P-cleavage of the cyclopropylcarbinyl radical, addition of the carbon-centered radical to the alkyne, ring closure of a vinyl radical via 5-exo-trig manner, and finally subsequent P-elimination of the thiyl radical, as shown in eq. 3.107 [272-276]. Here, PhSSPh acts as a catalyst, since the thiyl radical is regenerated. Aliphatic disulfides such as... 

Most studies involve reactions of carbon-centered radicals with alkenes and alkynes as radical traps. Heteroatom radical traps such as carbonyl groups, imines, and nitriles have received much less attention. Since radical reactions involving carbon-centered radicals and C=C bonds lead to the loss of the two participating functional groups, one of the advantages in radical reactions using heteroatom radical traps is to retain synthetically useful functionality for further manipulations. 

Photochemical addition reactions involving [2 + 2] additions between electron-deficient heteraryl rings and electron-rich alkenes and alkynes have been estab-lished. Reactions of carbon-centered radicals with pentafluoropyridine gives 4-substituted products, reflecting the nucleophilic character of the radical species" (Fig. 8.22). 

In ccHitrast to aIkynyliod(Miiiim salts, which have been used in organic synthesis for decades, EBX reagents have been used intensively only in the last 5 years. However, they have already made a strong impact in the synthesis of alkynes, as they allowed new transformations which were not accessible before. They were especially successful in transition metal catalysis, where they allowed the development of new C-H functionalization and domino reactions. They also demonstrated important advantages for the functionalization of acidic C-H bonds or carbon centered radicals. EBX reagents allowed new transformations with heteroatoms, such as the alkynylation of thiols, or presented distinct highly useful properties, for example in the alkynylation of tosyl amides, sulhnates, or phosphorus nucleophiles. 

An aryl radical generated from an unsubstituted quinazoline can perform radical addition into an alkyne. The resulting carbon-centered radical can propagate the chain by abstracting a hydrogen atom from another quinazoline. ... 

It is well known that simple alkanes are ready to undergo hydrogen abstraction to form carbon-centered radicals in the presence of radical initiators (TBHP, DTBP, K2S2O8, etc), and the resulting nucleophilic alkyl radicals are able to attack unsaturated chemical bonds, such as alkenes, alkynes, aromatic rings, and isocyanides (Scheme 2.38). In 2008, Li et al. introduced a novel [Ru(p-cymene)Cl2]2-catalyzed,... 

The facile photosensitized oxidation of tetraalkylstannanes (R4 n) and related group-14 compounds has been widely exploited by Mella and co-workers to form carbon-centered radicals. Photoinduced electron transfer from tetraalkylstannanes to a sensitizer, such as aromatic nitriles and esters (including tetramethyl pyromellitate, TMPM), affords a radical cation [R4 n] that can fragment to form an alkyl radical (R) together with the R3Sn+ cation. The alkyl radicals can then react with electron-poor alkenes, alkynes, aromatics, or the radical anion formed from the photosensitizer to form new carbon-carbon bonds. Careful choice of the photosensitizer can ensure that the radical anion selectively reduces the radical adduct (derived from addition to a double bond) rather than the first-formed alkyl radical (Scheme 5). 

Clive and coworkers have developed a new domino radical cyclization, by making use of a silicon radical as an intermediate to prepare silicon-containing bicyclic or polycyclic compounds such as 3-271 and 3-272 (Scheme 3.69) [109], After formation of the first radical 3-267 from 3-266, a 5-exo-dig cyclization takes place followed by an intramolecular 1,5-transfer of hydrogen from silicon to carbon, providing a silicon-centered radical 3-269 via 3-268. Once formed, this has the option to undergo another cyclization to afford the radical 3-270, which can yield a stable product either by a reductive interception with the present organotin hydride species to obtain compounds of type 3-271. On the other hand, when the terminal alkyne carries a trimethylstannyl group, expulsion of a trimethylstannyl radical takes place to afford vinyl silanes such as 3-272. 

In 1967, Heiba and Dessau reported perhaps one of the earliest examples of a radical cychzation cascade that is initiated by intermolecular addition of C-centered radicals to alkynes. Reaction of carbon tetrachloride with 1-heptynes 1 in the presence of benzoyl peroxide (BPO) as radical initiator resulted, among other products, in the formation of 1,1-dichlorovinylcyclopentane derivatives 2 in moderate yields (Scheme 2.1). °... 

Simultaneous introduchon of both sulfur and selenium functions into carbon-carbon unsaturated compounds via a radical mechanism is also demonstrated by selenosulfonahori [149] and selenothiocarboxylatiorl [150] (Scheme 15.70). In these addihon reactions, attack of sulfur-centered radicals at the terminal position of alkenes and the subsequent Sh2 reaction on the selenium lead to the formahon of anti-Markovnikov adducts regioselechvely. The selenosulfonahon can be apphed to a variety of unsaturated compounds, for example alkynes, allenes, and vinylcyclopropanes, and combination with the selenoxide syn-elimination procedure... 

Carbon-Nitrogen Bond Formation. Apart from the CAN-mediated reactions in which solvent (e.g., acetonitrile) incorporation results in carbon-heteroatom bond formation, the oxidative generation and subsequent addition of heteroatom-centered radicals to alkenes or alkynes provide means of direct construction of carbon-hetereoatom bonds. ... 

There are many reagents that add to alkenes only by radical-chain mechanisms. A number of these are listed in Table 10-3. They have in common a relatively weak bond, X—Y, that can be cleaved homolytically either by light or by chemical initiators such as peroxides. In the propagation steps, the radical that attacks the double bond does so to produce the more stable carbon radical. For addition to simple alkenes and alkynes, the more stable carbon radical is the one with the fewest hydrogens or the most alkyl groups at the radical center. 

In addition to cationic cyclizations, other conditions for the cyclization of polyenes and of ene-ynes to steroids have been investigated. Oxidative free-radical cyclizations of polyenes produce steroid nuclei with exquisite stereocontrol. For example, treatment of (259) and (260) with Mn(III) and Cu(II) afford the D-homo-5a-androstane-3-ones (261) and (262), respectively, in approximately 30% yield. In this cyclization, seven asymmetric centers are established in one chemical step (226,227). Another intramolecular cyclization reaction of iodo-ene poly-ynes was reported using a carbopaUadation cascade terminated by carbonylation. This carbometalation—carbonylation cascade using CO at 111 kPa (1.1 atm) at 70°C converted an acycHc iodo—tetra-yne (263) to a D-homo-steroid nucleus (264) [162878-44-6] in approximately 80% yield in one chemical step (228). Intramolecular aimulations between two alkynes and a chromium or tungsten carbene complex have been examined for the formation of a variety of different fiised-ring systems. A tandem Diels-Alder—two-alkyne annulation of a triynylcarbene complex demonstrated the feasibiHty of this strategy for the synthesis of steroid nuclei. Complex (265) was prepared in two steps from commercially available materials. Treatment of (265) with Danishefsky s diene in CH CN at room temperature under an atmosphere of carbon monoxide (101.3 kPa = 1 atm), followed by heating the reaction mixture to 110°C, provided (266) in 62% yield (TBS = tert — butyldimethylsilyl). In a second experiment, a sequential Diels-Alder—two-alkyne annulation of triynylcarbene complex (267) afforded a nonaromatic steroid nucleus (269) in approximately 50% overall yield from the acycHc precursors (229). 

The stereoelectronic effects of alkyne additions are not limited to anions, as radicals react similarly. The sulfonyl radical adds regio- and stereoselectively to the terminal carbon, giving the E-bromo vinylsulfone. NBO analysis shows that the radical center can act as both a donor and acceptor in interactions with the antiperiplanar C-S bond. In the radical intermediate formed by addition of tosyl radical to 1-hexyne, the donor character dominates. The energy of the n- CT was larger than the (Tj, g n (-27 vs. 7 kcal/mol, for the sum of a and p-spins. Figure 7.47). ... 

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