Allenes, cyclization with double functionalized

Allenes as an interesting class of unsaturated compounds have been explored in cyclizations with 2-iodoanilines and 2-iodophenols as well. In 1991, Larock and co-workers reported the cyclization of allenes with double functionalized arenes. Various five- and six-membered heterocycles were formed in high yields (Scheme 2.85). But the main problem is the long reaction time one or two days are usually needed. 

The examples illustrated in the almost 100 schemes in this chapter demonstrate how versatile donor-substituted allenes can be in synthetic processes. The major applications concern addition reactions and cycloadditions to the allenic double bonds, which furnish products with valuable functional groups. Of particular interest are metalations - usually at C-l of the allene unit - followed by reactions with electrophiles that deliver compounds which can often be used for cyclization reactions. A variety of highly substituted and functionalized heterocycles arises from these flexible methods, which cannot be obtained by other reactions. Many of these transformations proceed with good regioselectivity and excellent stereoselection. 

The addition of allenyl ether-derived anions to Weinreb [4] or to morpholino amides [5] follows a slightly different pathway (Eq. 13.2). For example, the addition of lithioallene 6 to Weinreb amide 7 at -78 °C, followed by quenching the reaction with aqueous NaH2P04 and allowing the mixture to warm to room temperature leads to cyclopentenone 9 in 80% yield [6]. The presumed intermediate of this reaction, allenyl vinyl ketone 8, was not isolated, as it underwent cyclization to 9 spontaneously [7]. These are exceptionally mild conditions for a Nazarov reaction and are probably a reflection of the strain that is present in the allene function, and also the low barrier for approach of the sp and sp2 carbon atoms. What is also noteworthy is the marked kinetic preference for the formation of the Z-isomer of the exocyclic double bond in 9. Had the Nazarov cyclization of 8 been conducted with catalysis by strong acid, it is unlikely that the kinetic product would have been observed. 

Polyfluoroalkyl-functionalized cyclobutenes with an exo cyclic double bond have been shown to form from 3-aza-l,5-enynes via a thermal aza-Claisen rearrangement to give an allene-imine intermediate and subsequent cyclization to give the cyclobutene core (Scheme 32)... 

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