Cyclization Barbier reaction

In a similar manner, starting from 2-methylchloride-naphtho[l,8-de][l,2,3]triazine and magnesium, via a novel sonication-promoted Barbier reaction, an a-aminomethyl carbanion equivalent is generated which reacts in situ with a variety of carbonyl compounds. Subsequent catalytic hydrogenolysis of the triazine moiety yields the corresponding amines <00TL4685>. Sterically controlled regiospecific cyclization of aldose-5-ethyl-l,2,4-... 

Barhier cyclization The Barbier reaction has been used for cyclopentenone annclation.5 Thus a-allylcycloalkanones are converted into the iodo ketones 1, which on treatment in THF with magnesium activated by HgCl2 are converted into bicycloalkanols (2) in moderate to good yield. Formation of cw-fused products is greatly favored. The reaction gives poor yields when extended to annelation of six-und scvcn-mcmbcred rings. 

An intramolecular 2-alkylation was also observed in a sulfonyl free radical induced addition-cyclization <95SL763>. A key intermediate in a new synthesis of pallescensin A (a biologically active labdane diterpene) was prepared by a cationic cyclization reaction with a furan <95SYN1141>. The sonochemical Barbier reaction was extended to carboxylate salts. 2-Furanylketones 10 can be obtained by sonication of a mixture of furan, lithium carboxylate, an alkylchloride, and lithium in THF <95JOC8>. 

The classical (Grignard-like) mechanism for Barbier reactions involves the primary formation of an Sm-alkyl species via halogen abstraction and subsequent reduction of the alkyl radical formed after the first electron transfer. Be that as it may, the Barbier reaction can be used to construct complex polycyclic target molecules, e.g. the synthesis of tetraquinanes from diquinane precursors by two independent intramolecular cyclization steps (Scheme 24) [83]. 

Exceptionally clean cyclization can be accomplished by utilizing conjugated enones as precursors for the Barbier reaction (equation 43). High diastereoselectivity is achieved in these reactions, and under the mild conditions required for cyclization the TMS ether protecting group remains intact. It is also interesting that a neopentyl halide is effective in the cyclization. This result would appear to exclude an 5N2-type displacement of an organic halide by a samarium ketyl as a possible mechanism for the Smh-promoted intramolecular Barbier reaction. 

Evidence for a radical coupling mechanism (as opposed to a carbanionic carbonyl addition mechanism) in the intramolecular Smh-promoted Barbier reactions has come from studies on appropriately functionalized substrates in the 3-keto ester series. It is well known that heterosubstituents are rapidly eliminated when they are adjacent to a carbanionic center. Indeed, treatment of a 3-methoxy organic halide (suitably functionalized for cyclization ) with an organolithium reagent leads only to alkene (equation 48). No cyclized material can be detected. On the other hand, treatment of the same substrate with Sml2 provides cyclized product and a small amount of reduced alcohol, with none of the alkene detected by gas chromatographic analysis (equation 49). ... 

B.M. Trost and co-workers conducted studies toward the total synthesis of saponaceolide B, an antitumor agent active against 60 human cancer cell lines. " One of the challenging structural features of this compound was the cis 2,4-disubstituted 1-methylene-3,3-dimethylcyclohexane ring. The key steps to construct this highly substituted cyclohexane ring were a diastereoselective Barbier reaction to install a vinyl bromide moiety followed by an intramolecular Heck cyclization reaction. 

Stypodiol, epistypodiol and stypotriol are secondary diterpene metabolites produced by the tropical brown algae Stypopodium zonaie. These compounds display diverse biological properties, including strong toxic, narcotic, and hyperactive effects upon the reef-dwelling fish. In the laboratory of A. Abad an efficient stereoselective synthesis of stypodiol and its C14 epimer, epistypodiol, was accomplished from (S)-(+)-carvone. The key transformations in the synthesis of these epimeric compounds were an intramolecular Diels-Alder reaction, a sonochemical Barbier reaction and an acid-catalyzed quinol-tertiary alcohol cyclization. 

Curran, D. P., Fevig, T. L., Totleben, M. J. Sequential radical cyclization-organometallic addition. The mechanism of the samarium(ll) mediated Barbier reaction in the presence of hexamethylphosphoric triamide. Syn/ett 1990, 773-774. 

Lantanides and Sml2 specifically in carbon-carbon bond formation or for functional group transformation (cyclization, Barbier type reaction, intramolecular coupling, aldol, Evans, Tishenco). 

Diiodosamarium induced an intramolecular Barbier reaction, under mild conditions (room temperature), in the presence of a catalytic amount of iron tris(dibenzoylomethane [Fe(DBM)3]. In this way many bicyclic tertiary alcohols were prepared. These conditions were also convenient for the cyclization... 

Vinylogous Barbier reaction,4 Smlj (2 equiv.) can effect cyclization of the unsaturated iodo ketone 1 in THF containing DMPU (or HMPA) to give a bicyclic samarium enolatc (a) that can be trapped by an aldol reaction. 

Baeyer-Villiger reaction, 456 baker s yeast reduction, 14 Barbier cyclization reactions, 138 Barbier reaction, 138 BBrj, 227... 

Barbier reactions. Allylic alcohols are produced from alkenyl halides and carbonyl compounds on mediation by Sml2. This process includes the preparation of the Baylis-Hillman adducts from a-bromoacrylamides and carbonyl compounds. Barbier reaction involving 1-chloromethylbenzotriazole affords alcohols that are valuable synthetic intermediates. iV-(co-Iodoalkyl)-0,0 -bis(f-butyldimethylsilyl)tartrimide undergoes cyclization quite efficiently and the reaction has been applied to a synthesis of (+)-lentiginosine. ... 

In the course of our work on large-ring compounds, we were looking for a new access to cheap precursors for cyclization. In this respect, the sonochemical Barbier reaction of... 

Haloketones in Barbier Reactions, The below introduction in an article on a newly developed cyclization reaction was published in 1970 [72] ... 

Haloalkylphosphonates in Barbier Reactions, Di-n-butyl 5-bromopentyl-l-phos-phonate reacted with magnesium (in the presence of magnesium bromide) to form the cyclized product [83] ... 

The results of intramolecular Li-Barbier reactions (cyclization reactions) with 5-bromo-l-cyano-2,2-dimethylpentane and the corresponding 6-bromohexane were rather disappointing [22]. The expected 2,2-dimethylhexanone was formed in only 31% yield ... 

Intermediacy of Organometallics. It is illustrative to quote some of the final words of a rather recent paper [68] on the magnesium-induced cyclization of 2-(3-iodopropyl)-cycloalkanones, an intramolecular Barbier reaction (see also Sect. 2.4.2, p, 46 in chap. 2) ... 

Allenols may be carbonylated under quite different conditions. Using Rus (CO)i 2 as the catalyst, unsaturated lactones can be synthesized efficiently." The reaction may also be extended to lactams." This cyclization, combined with an intramolecular propargylic Barbier reaction has been used in syntheses of mintlactone 4.111 from allenol 4.110 (Scheme 4.43)" " and its diastereoisomer, isomintlactone," as well as the stemona alkaloid, stemoamide 4.115 from allenol 4.113 (Scheme 4.44)," and in the skeleton of stenine." A different synthesis of stemoamide can be found in Chapter 8, Scheme 8.112. 

Sml2-induced Barbier reaction also takes place upon photoirradiation (Scheme 2.33) [93]. When o-chlorophenyl aUyl ether (43) is reduced in the presence of diethyl ketone with Sml2 upon photoirradiation, a cyclic ether is produced in 72 % yield. Most probably, the cyclic ether is formed by 5-exo cyclization of the aryl radical followed by reduction with Sml2 and the subsequent addition of alkylsamarium species to diethyl ketone. 

This hypoiodite reaction can also be used for ring expansion of cyclic ketones.2 Thus Barbier cyclization of a-(w-iodopropyl)cyclododecanone (3) furnishes the bicyclic alcohol 4, which undergoes regioselective cleavage to a 15-membered iodo... 

Bacycr-Villiger oxidation, 122, 124, 168 Bamford-Stevens reaction, 565 Barbier cyclization, 307-308 Beckmann rearrangement, 168, 245-246. 427-428, 429, 446, 539-540 Bentonite, 237, 441... 

In some cases, such as with the allylic bromosulfone 17, the best reaction conditions to add to imines are obtained under Barbier conditions, reaction in this manner gives the unsaturated aminosulfone 18. Treatment with catalytic potassium hydride, results in a 5-endo-trig cyclization to form the pyrrolidine 19 in 65% yield (Scheme 1.8).25,26... 

The carbolithiation reaction followed by additions of various reagents usually renders a mixture of open-chain and cyclic products, as observed in the conventional Barbier reaction122. Nevertheless, Yus and coworkers40 found that when the alkene is substituted by aromatic moieties, only the cyclization reaction takes place (Schemes 59 and 60). They have previously found that the use of an excess of lithium powder and a catalytic amount of an arene (4,4 -di-tert-butylbiphenyl, DTBB, is most commonly used) is an adequate procedure to carry out chlorine-lithium exchange under very mild reaction conditions123. 

When (Z)-6-chloro-l-phenylhex-l-ene 200 was lithiated under DTBB catalysis, the cyclized product 202 was always obtained either at —78 or at —30 °C. After the first chlorine-lithium exchange a carbolithiation took place to yield the intermediate 201, which by reaction with electrophiles, E, and final hydrolysis gave products 202 (Scheme 60). At —78 °C the reaction under Barbier-type conditions did not work. Also in this case, the corresponding reduced product (202 with E = H) was the main by-product detected. 

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