Furan-substituted allenes synthesis

A new method for the synthesis of furan-substituted allenes via Cu(I)-catalyzed coupling of conjugated ene-yne-ketones with terminal alkynes was developed. A copper carbene migratory insertion was proposed as the key step in this transformation, with conjugated ene-yne-ketones as carbene precursors (14OL4082). 

Carbonyl compounds also react with allenes and, in fact, the first example of a gold-catalyzed addition of a nucleophile to allenes was the formation of lurans from allenones. The reaction was applied by Gevorgyan to the synthesis of substituted furans and in the case of bromide-substituted allenes halide migration was observed. Similar additions of... 

An example of palladium-catalyzed furan synthesis utilizing allenes as starting materials was reported, in which 2,4-disubstituted-2,3-butadienoic acids and 1,2-propadienyl ketones were used and 2,4-disubstituted furans were produced. The reaction may proceed via a matched double oxypalladation-reductive elimination process <04CEJ2078>. In a similar cycloisomerization of substituted allenes to tri- and tetrasubstituted furans with regioselectivity, the allenes were produced in situ from acyloxy-, phosphatyloxy- and sulfonyloxy-substituted alkynylketones via a 1,2-migration of such substituents catalyzed by CuCl or AgBF <04AG(E)2280>. 

Protection of the allenic group, by formation of its Diels-Alder adduct with furan, enables otherwise incompatible chemical modification of the a-allenic substituents to be performed. Thermal regeneration of the allenic moiety at 450—510 C completes the synthesis of novel substituted allenes, such as the hitherto unknown a-allenic oximes. 

The development of intramolecular Diels-Alder (IMDA) reactions for the synthesis of natural products (80CR63) and the facility with which substituted furans can be assembled have been reviewed 840R(32)1, 86CRV795, 87CSR187, 90SL186). Thus, IMDA product from the propargyl sulfone shown in Scheme 43 proceeds via the allene and was converted subsequently into the benzenoid sulfone under base catalysis (92CC735). 

As demonstrated below, a Lewis acid-mediated reaction was utilized in the synthesis of dihydro[b furan-based chromen-2-one derivatives from l-cyclopropyl-2-arylethanones and allenic esters <070L4017>. The TiCh-catalyzed anti-Markovnikov hydration of alkynes, followed by a copper-catalyzed O-arylation was applied to the synthesis of 2-substituted benzo[6]furan <07JOC6149>. In addition, benzo[6]furan-based heterocycles could be made from chloromethylcoumarins <07SL1951>, substituted cyclopropanes <07AGE1726>, as well as benzyne and styrene oxide <07SL1308>. On the other hand, DBU-mediated dehydroiodination of 2-iodomethyl-2,3-dihydrobenzo[6]furans was also useful in the synthesis of 2-methylbenzo[Z>]furans <07TL6628>. 

Allenes are rarely used. The trimethylsilyl ester of prop-2,3-diendioic acid adds but once to 5-substituted furans giving adducts (17) intended for use in the synthesis of Rauwoljia alkaloids.40... 

The first carbon addition to allenes catalyzed by gold was described by Hashmi and was the addition of furans to allenones, a reaction that is discussed as a conjugate addition to carbonyls. Then the annulation of 2-allenyl indoles was described (equation 111)and an enantioselective version was later developed for terminal allenes. Then Nelson described the cyclization of an N-substituted pyrrol in the synthesis of (—)-Rhazinilam (equation 112). In that case, gold notably improved the yields and selectivities obtained with Pd(II) or Ag(l), and gave complete retention of the chiral information of the allene. The most recent report is on the hydroarylations of allenes with gold-covered substituted benzenes as substrates. ""... 

Another cycloaddition, in which this time the silyl enol ether functions as a dienophile, is the SnCl4-catalysed addition of butadiene to (180 R = Me) giving (181). If R = H in the starting material a 4 + 3 reaction takes place, producing the seven-membered ring (182). Flash-vacuum thermolysis of P-keto-trimethylsilyl enol ethers has been used in a substituted furan synthesis, and the same process has been used to prepare a-allenic acids (183) from siloxy-dienes. ... 

Benzannulated enyne-allenes with heteroatomic substitution in the allene branch are precursors of the indeno-fused heteroatomic systems that are suitable for use in pharmacological applications. Introducing a heteratomic substituent in the allene branch of the enyne-allenes promotes a cascade of reactions that lead to derivatives such as 1 OH-indeno [1,2-g] quinoline, 9H-fluorene[2,3- ] furan, 9H-fluorene[2, 3-b]thiophene, 5H- and 6H-indeno[2,l-/]indolizine [278]. An example of this strategy is the synthesis of indeno-fused derivatives of quino-lizinium salts 3.558 (Scheme 3.41) [278]. 

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