Radical cyclization catalytic

Norton has recently combined these key-steps with the activation of H2 by CpCr (CO)3 to very elegant tin-free and catalytic radical cyclization mediated by H2 that is highlighted in Scheme 7 [28, 29]. 

Early examples of catalytic radical cyclizations were provided by Okabe and coworkers, who subjected 2-bromoethyl propargyl ethers or bromoacetaldehyde propargyl acetals 257 to complex 255 as a catalyst and sodium borohydride as the stoichiometric reducing agent (Fig. 63, Table 5, entry 1) [307, 308]. 

Scheme 14.31 Del Moral and Barrero s total synthesis of (+)-seco-C-oleanane (206) using a catalytic radical cyclization.

In an effort to identify a more stereoselective route to dihydroagarofuran (15), trimethylsilylated alkyne 17 was utilized as a substrate for radical cyclization (Scheme 2). Treatment of 17 with a catalytic amount of AIBN and tri-n-butyltin hydride (1.25 equiv) furnishes a mixture of stereoisomeric vinyl silanes 18 (72% combined yield) along with an uncyclized reduction product (13% yield). The production of stereoisomeric vinyl silanes in this cyclization is inconsequential because both are converted to the same alkene 19 upon protodesiiyiation. Finally, a diastereoselective di-imide reduction of the double bond in 19 furnishes dihydroagaro-... 

Alkyl Co oxime complexes have been used as chain transfer catalysts in free radical polymerizations.866,867 Regioselective hydronitrosation of styrene (with NO in DMF) to PhCMe=NOH is catalyzed by Co(dmg)2(py)Cl in 83% yield.868,869 Catalytic amounts of the trivalent Co(dmg2tn)I2 (192) (X = I) generate alkyl radicals from their corresponding bromides under mild reaction conditions, allowing the selective preparation of either saturated or unsaturated radical cyclization products.870... 

Germanes are also used for the reduction of various organic halides at ambient temperature under Et3B/C>2 initiation. For example, tri-2-furylgermane mediated radical cyclizations of aryl iodides proceed in good yields (Scheme 6, Eq. 6a) and are also possible with NaBH4 in the presence of a catalytic amount of triphenylgermane (Eq. 6b) [ 16]. 

Bromo-enamides have been reported to give radical cyclization in excellent yields (82-99%) to p-lactams using catalytic amounts (30%) of tripyridylamine (TPA) copper halide complex [184]. The p-lactam developed under mild conditions via 4-exo bromine atom transfer and subsequent elimination of the tertiary bromide that could be readily achieved by reaction with DBU (Scheme 83). 

In summary, intramolecular radical cyclization reactions onto aromatic rings can provide quick access of otherwise not so easily assembled Ca0. -C.ryi bonds, although the yields are generally low and the process suffers from a lack of regioselectivity. Noticeably, Crich found that a catalytic amount of benzeneselenol, which can also be generated in situ reduction of diphenylselenide with stannane [57]. This method should find synthetic utility in intramolecular radical addition to arenes. 

The same radical cyclization can be performed using a more simplified vitamin B12 model, such as Z w(dimethylglyoximato)(pyridine)Cobalt chloride Co3+ Cl -Py complex (B), as shown in eq. 11.3. Treatment of propargyl P-bromoethyl ether (3) with NaBH4 and a catalytic amount of the cobalt complex (B) provides fi-exo-methylene tetrahydrofuran via 5-exo-dig manner [2-7]. 

Despite these slight shortcomings, the development of the catalytic conditions constitutes a major conceptual advance in the field of radical cyclizations. 

The major problem with using Wilkinson s catalyst is that it also constitutes an excellent hydrogenation catalyst [56]. Thus, alkynes and terminal alkenes are not tolerated under the conditions of the coupled catalytic cycles. This implies that radical cyclizations terminated by a CHAT cannot be carried out under these conditions. 

Since the introduction of the titanocene chloride dimer 67a to radical chemistry, much attention has been paid to render these reactions catalytic. This field was reviewed especially thoroughly for epoxides as substrates [123, 124, 142-145] so only catalyzed reactions using non-epoxide precursors and a few very recent examples of titanium-catalyzed epoxide-based cyclization reactions, which illustrate the principle, will be discussed here. A very useful feature of these reactions is that their rate constants were determined very recently [146], The reductive catalytic radical generation using 67a is not limited to epoxides. Oxetanes can also act as suitable precursors as demonstrated by pinacol couplings and reductive dimerizations [147]. Moreover, 5 mol% of 67a can serve as a catalyst for the 1,4-reduction of a, p-un saturated carbonyl compounds to ketones using zinc in the presence of triethylamine hydrochloride to regenerate the catalyst [148]. 

Radical cyclizations catalyzed by 67a require the regeneration of the titanocene catalysts by a stoichiometric reductant, such as manganese. When 10 mol% of substituted cyclopentadienyltitanium complex 47e is applied instead truly catalytic cyclization sequences of epoxides 86 are possible (Fig. 25) [160]. Reductive radical generation from 86 promoted by titanocene chloride 67e and subsequent 5-exo cyclization of radical 86A generates a titanoxy cyclopentylalkyl radical 86B. Since the electron-poor titanocene chloride 67e reduces the tertiary radical 86B only sluggishly, its extended lifetime allows for a 1,5-SHi affording the bicyclic tetrahy-drofuran ring system 87. At the same time catalyst 67e is liberated. The reaction... 

Alkyl and aryl radical cyclizations were developed using catalytic amounts of MnCl2 and butylmagnesium bromide as a stoichiometric reductant (Fig. 44)... 

Oshima s group reported the first example of a tandem radical cyclization/intermo-lecular Heck reaction in 2002 (Fig. 60) [289]. Iodoacetaldehyde allyl acetal 242a was treated with styrene 243, catalytic amounts of CoCl2(dpph), and trimethylsi-lylmethylmagnesium chloride 224 as a stoichiometric reducing agent. 4-Cinnamyl-butyrolactol 244 was isolated in 50% yield (cf. Fig. 54). 

Inspired by Nature, hydroxocobalamine 247 (X=OH) itself or modified vitamin B12 derivatives (review [331]) were probed as catalysts for radical cyclizations. This methodology is mediated by light and electrochemical or chemical reduction to close the catalytic cycle. It was applied to total syntheses of forskolin 280 by Pattenden [325] (Fig. 67, entry 13) as well as of jasmonate 284 and prostaglandin precursors 287 by Scheffold (entry 14) [326, 327], Starting materials were bromoacetaldehyde cyclohexenyl or cyclopentenyl acetals 278, 281, or 285, which cyclized in the presence of 247 to annulated butyrolactols 279, 283, or 287. In the forskolin synthesis the cyclized radical was reduced directly, while a radical addition ensued in the presence of acetoxyacrylonitrile 282 or ynone 286 in... 

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