Barbier-type cyclization

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

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

More than sixty years later this Barbier-type cyclization reaction was repeated [74] with the corresponding bromide methylcyclopentanol was isolated in 65% yield. 

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. 

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. 

These examples again have some mechanistic implications in that they appear to rule out cyclization via 5n2 displacement of the halide by a samarium ketyl. However, one cannot distinguish between a mechanism based on allylsamarium addition to the carbonyl versus an electron transfer mechanism as outlined for the alkyl hdide substrates above. Both mechanisms allow for isomerization of the double bond (via 1,3-allylic transposition in the case of an allylmetallic, or configurational instability in an allylic radical in a diradical coupling mechanism) and also provide reasonable routes for generation of butadiene. Further mechanistic work is clearly required in order to provide a more detailed understanding of all of these intramolecular Barbier-type reactions. 

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

Cooper et al. reported that the cascade reaction of the palladium-catalyzed cyclization and the Barbier-type allylation of the 1,3-diene-aryl iodide 514, the aldehydes 515, and indium gave the heterocycles 516 in good yields (Scheme 154).220b The reaction proceeds through oxidative addition of a C—I bond of 514 to Pd(0) and subsequent insertion of a double bond of 517 to give the jr-allylpalladium intermediate 518. Transmetalation of the jr-allylpalladium 518 with indium leads to the allylindium complex 519, and the following reaction with the aldehydes 515 gives 516. 

Barbier-type reactions. Cyclization of iodoketones in which the iodine atom is allylic or vinylic can be accomplished with the same combination of BujSnSiMej and CsF. ... 

In 1968, sodium was successfully applied [12] for the following cyclization reaction (intramolecular Barbier-type reaction) which had previously failed with magnesium ... 

A Lewis acid push-pull mechanism proposed for the magnesium bromide promoted Barbier-type intramolecular cyclization of Grignard reagents derived from halo-substituted acetals, ketals, and orthoesters as depicted in (Scheme 9). Stereoselective addition of chiral a-aminoorganometallics to aldehydes has been reviewed. Chiral 1,4-dihydropyridines have been synthesized with good regio- and... 

The intramolecular variant of the chrDmium(II) ion mediated Barbier-(jiignard-type addition reaction was first described by Still and Mobilio in an elegant synthesis of ( )-Aspeidiol (122 R = H). Chro-mium(II)-mediated cyclization of (121 R = Bn) provided a 4 1 mixture of (122) and (123) in 64% yield (equation 50). The relative topicity of the process is Ik. This result is in acco with a syncliiud chair transition structure (124) in which both hydrocarbon chains diverge from the reacting centers pseudo-... 

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. 

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