Cyclization of alkenes

Baddeley also investigated the cyclization of alkenes in the NaCl/AlCl3 molten salt. An example is given in Scheme 5.1-47 [77]. 

Free radical cyclization of alkenes with tin or mercury halides... 

Palladium-catalyzed cyclization of alkenes and alkynes were reported by Balme and co-workers.143 144 Intramolecular carbopalladation occurs to give polycyclic compounds. It has been shown that the nucleophile type has a large influence on the cyclization process. Both 5-exo- and 6-endo-cyclization are observed for substrates with nitrile (116 and 118) and ester (120, 122, and 124) substituents, respectively (Scheme 36). When a mixed nucleophile (CN and C02Me) is used, a mixture of 5-exo and 6-endo products is obtained. The chemoselectivity is controlled by the size of the nucleophile used. The stereochemistry of the initial double bond plays an important role on the stereoselectivity of the cyclization. (Z)-olefins (118 and 120) and (/. )-olefins (116 and 124) afford as- (119 and 121) and trans-cyclization products (117 and 123), respectively. 

Several routes to the pyrrolo[l,2-f][l,2,3]triazole skeleton have been described. Intramolecular dipolar cycloaddition of azido-alkenes or alkynes seems to be the most convenient process, although the cyclization efficiency seems to be highly substrate dependent (Scheme 16) <2002JA2134, 2003T1477, 2005SL2187, 2005TL8639>. The formation of this bicyclic system by an intramolecular Heck reaction is an attractive alternative. The recent syntheses of sulfamides by intramolecular cyclization of alkenes or allenes offer a complementary route to the classical... 

Sames et al. have reported the intramolecular cyclization of alkene-amide substrates catalyzed by [Ir(COE)2Cl]2 and the A-heterocyclic carbene ligand, N, A -bis-(2,6-diisopropylphenyl)-imidazolyl, via olefin insertion following oxidative addition of an sp C-H bond (Scheme 11) [117]. 

Scheme 11 Cyclization of alkene-amide via sp C-H Bond cleavage...

The first examples of alkylation reactions in molten salts were reported in the 1950 s. Baddeley and WiUiamson performed a number of intramolecular cycHza-tion reactions [76] (Scheme 5.1-46), carried out in mixtures of sodium chloride and aluminium chloride. The reactions were mn at below the melting point of the pure salL and it is presumed that the mixture of reagents acts to lower the melting poinL Baddeley also investigated the cyclization of alkenes in the NaCl/AlCl3 molten salL An example is given in Scheme 5.1-47 [77]. 

Alternately, CpjZr can also be prepared by the reaction of Cp2ZrCl2with two equivalents of n-BuLi at —78°C E.-I Negishi, F. K. Cederbaum and T. Takahashi, Reaction of zirconocene dichloride with alkyl lithiums or alkyl Grignard reagents as a convenient method for generating a zirconocene equivalent and its use in zirconium promoted cyclization of alkenes, alkynes dienes, eneynes and diynes, Tetrahedron Lett. 27 2829 (1986). 

Figure 9.2. Oxidative cyclization of alkenes with polystyrene-bound selenyl bromide [8,9,12-14].

Cyclizations of alkenic amines and imines using organoiron complexes to generate bicyclic 3-lactams are discussed in Chapter 3.1 of this volume. Examples of heterocyclizations of alkenic NA/-dialkylamine and pyridine derivatives to form cyclic quaternary ammonium salts are cited in the Staninets review.Ic A cyclization of an enol thioether has been used to generate a thiazolidine intermediate used in cephalosporin synthesis (equation 131).262... 

The formation of bicyclo compounds by the radical cyclization of alkenes with strategically placed phenylseleno groups, promoted by Bu3SnH, occurs in high yields and gives... 

Cyclization of alkenes.1 This Ziegler-Natta polymerization catalyst can effect intramolecular cyclization of unactivated alkenes. Thus transmetallation of a Grignard reagent (1) with Cp2TiCl2 results in a titanium complex (2), which on... 

Tributyltin hydride-mediated radical cyclization of alkenes 403 (R = OPh or OAc) led to three types of product (Equation 58). The yields of the 4/6/6 ring system were low and the ratio of the isomers varied with the nature of R but the major product was 404 in each case <1996TL1363>. 

A representative and interesting example for the dependency on the product s ring-size is the PET-cyclization of alkene-silylamine derivatives as described by Pandey et al. (Sch. 33) [35a]. 1,5-Cyclization (19, n= 1) predominantly gave the ds-isomer whereas the corresponding 1,6-cyclization (19, n — 2) yielded the opposite trans-isomer, respectively. Both findings were rationalized by chair-like transition states. 

Palladium(II)-promoted oxidative cyclization of alkenes bearing tethered nucleophiles represents an intramolecular variant of the Wacker reaction. These reactions, which typically generate five- and six-membered heterocycles, have been the subject of considerable interest in organic chemistry [89-96]. Contemporary interest centers on the development of enantioselective examples [95,97] and reactions that employ dioxygen as the sole oxidant for the Pd catalyst [92-96]. 

As already mentioned, the nature of the selenium electrophile, the counter ion, solvents, and external additives coordinating to the electrophilic species influence the course of such cyclizations. They can also be used to control such processes with high degrees of efficiency. This has recently been demonstrated by the selective cyclization of substrate 58, which contains an alcohol and a carboxylic acid functionality as internal nucleophiles. Depending on the cyclizing nucleophile, electrophilic 5-m -cyclizations of alkene 58 can lead to two different... 

Radical cyclization of alkenes 124 in refluxing benzene with Bu3SnH (1.5 equiv) and a catalytic amount of 2,2 -azobisisobutyronitrile (AIBN) furnished the respective crystalline 2-benzoxocine derivatives 125 in 50-60% yield (Scheme 29) <1997CC2139>. 

The early woric with thiyl radicals primarily involved the intramolecular cyclization of alkenes. The reaction appears to be useful since high yields and stereoselective formation of products are observed (equation 7). Under a variety of conditions the diallyl diester (12) produces a 6 1 mixture of stereo-isomeric cyclopentanes (13) and (14) in high yield. ° When enynes are treated with thiyl radicals, low to moderate yields of addition products are observed (equation 8). ... 

Both disubstituted alkynes (Chapter 3.3, this volume) and isolated terminal double bonds may be reduced by alkali metals in NH3, but isolated double bonds are usually stable to these conditions. However, 16,17-secopregnanes (10 equation 8) afford mixtures of cyclization products (11) and (12) in 61% to 80% yield with Na naphthalenide-THF, Na-NHs-THF, Na-THF or Li-NHs-THF. With Na-NHa-THF-r-butyl alcohol, a 91% yield of a 72 28 mixture of (11) (12) (R = Me) is obtained. This type of radical cyclization of alkenes and alkynes under dissolving metal reduction conditions to form cyclopentanols in the absence of added proton donors is a general reaction, and in other cases it competes with reduction of the carbonyl group. Under the conditions of these reactions which involve brief reaction times, neither competitive reduction of a terminal double bond nor an alkyne was observed. However, al-lenic aldehydes and ketones (13) with Li-NHs-r-butyl alcohol afford no reduction products in which the diene system survives. ... 

Aryl radicals participate in radical cyclization reactions when the aromatic ring has an alkene or alkyne substituent. o-Iodo aryl allyl ethers cyclize to benzofuran derivatives, for example, when treated with AIBN, aqueous H3PO2 and NaHCOs in ethanol. Cyclization of an o-bromo-A-acyl aniline (a methacrylic acid derivative) with AIBN/BusSnH gave an indolone under the typical conditions used for cyclization of alkenes. 

The efficient activation of oxime sulfonates by organoaluminum reagents enables the intramolecular cyclization of alkenic oxime mesylates, which involves the electrophilic addition of the intermediate ni-trilium ion to the double bond. This results in the direct formation of a wide variety of structurally diverse carbocyclic and heterocyclic systems. Four distinct cyclization modes, i.e. endo(B)-endo, endo(B)-exo, exo(B)-endo and exo(B)-exo are possible, as shown in Scheme 4P The values in parentheses refer to the yields obtained using SnCU. 

Similar studies of the cyclization of alkene 81 revealed that when ( )-81 is used the effect is reproduced, although the ee s of the enantiomer obtained when using PMP are low (30 to 40%). In contrast, when (Z)-81 is used in conjunction with (i )-BINAP both sets of conditions give the expected (l )-enantiomer of 82 with good yields and excellent (>90%) ee s [68]. These results appear to suggest that the observed geometry effect (identical to that observed by Shibasaki et al. 

Related cyclizations of alkenes and electrophilic iminium ion intermediates such as A(-tosylimini-um - 9 and iminomalonate salts, 7i although outside the scope of this chapter, have been employed for assembling a variety of azacyclic materials. 

Some 2//-pyrans were obtained by cyclization of alkenic acetylenes after their activation involving C=C — C=C exchange in initial reaction steps. Thus, diacetylenic alcohol PhCH(OH)C=C—C=CPh (56) was found to cyclize to 2//-pyrans readily after the addition of secondary amines RR NH (82CZ296). Similarly, acetylenic ketone PhCOC=C—CH=CHOMe (57) gave appropriate 2//-pyrans after the addition of aqueous bromine or benzthiamide (83AP454). 

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