Barbier cyclization

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... 

Barbier cyclization (cf. 11, 307-308).- Sml, is effective for intramolecular cycli-zation of ot-(co-iodoalkyl)cycloalkanones to bicyclic alcohols. Yields can be improved by addition of Fe(IIl) catalysts such as tris(dibenzoylmethane)iron (6, 259). Cyclizations induced with ytterbium(ll) iodide are also stereoselective. 

Molander, G. A., Le Huerou, Y., Brown, G. A. Sequenced Reactions with Samarium(ll) Iodide. Sequential Intramolecular Barbier Cyclization/Grob Fragmentation for the Synthesis of Medium-Sized Carbocycles. J. Org. Chem. 2001,66,4511-4516. 

Our initial efforts in Barbier cyclization reactions were rapidly... 

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

Substituted -keto esters also provide excellent substrates for the intramolecular Barbier cyclization (eq 18). Diastereoselec-tivities are typically quite good but are highly dependent on substituent and solvent effects. 

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-... 

Barbier-type cyclization of a-(>a-iodoalkyl)- -keto esters or amides. 

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. 

Scheme8.2. Palladium-mediated Barbier-type cyclization of a bromoaryl ketone [37],...

Aryl radical cyclization.10 Sml2 in HMPA/THF at 25° can effect cyclization of l-allyloxy-2-iodobenzene to a Sm(III) intermediate (a) that can be trapped by electrophiles, including aldehydes or ketones. The report suggests that a similar mechanism operates in the Barbier-type coupling generation of an alkyl radical followed by formation of RSml2, which adds to a carbonyl compound to form an adduct that is hydrolyzed to an alcohol. 

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>. 

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... 

Subsequent exposure of geminal dibromide 62 to BU3S11H provided the desired ester 63 via a stereocontrolled cyclization-debromination tandem sequence. Finally, Barbier-Wieland degradation and hydrogenolytic debenzylation of ester 63 afforded 5a-carba-D-fructofuranose 64 in excellent yields. In a preliminary enzymological study, its 6-phosphate derivative showed to be an interesting substrate for the enzymes of the glycolysis pathway. 

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. 

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]. 

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