Allenyl Nazarov cyclization

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. 

A very unusual Nazarov cyclization of propargyl vinyl ketones has been reported by Hashmi et al. (Eq. 13.16) [18]. Propargyl alcohol 50 was oxidized to ketone 51 with the Dess-Martin periodinane. Attempts to purify 51 by column chromatography on silica gel led to cyclopentenone 53 in 59% isolated yield. This suggests that the solid support catalyzed the isomerization of 51 to allenyl vinyl ketone 52, which was not isolated, but which underwent spontaneous cyclization to 53. This result is consistent with earlier observations of the great ease with which allenyl vinyl ketones undergo the Nazarov reaction (cf. 8, Eq. 13.2). 

Q -electron-donating effect of fluorine to control the regiochemistry (Scheme 3). Analogous to silicon, tin is also used to direct the Nazarov cyclization. " The interrupted Nazarov reaction has been developed by West et al. to extend the reaction of the cationic endocyclic intermediate with carbon nucleophiles. Furthermore, this reaction has been extended to imino-Nazarov cyclization of vinyl allenyl imine. ... 

As opposed to these P-sp -hybridized systems, allenyl and cumulenyl substrates (P-sp-hybridized) exhibit excellent reactivity in the Nazarov cyclization. This enhanced reactivity is thought to derive from two factors Minimization of steric interactions at the P-position (increasing the... 

Elegant work by Tius and co-workers has demonstrated that the transfer of asymmetry need not be from an sp hybridized carbon atom. Instead, they have reported examples of the controlled Nazarov cyclization of allenyl vinyl ketones. In one such example, in situ formation of 67 resulted in efficient formation of cyclopentenone 68 with > 95% chirality transfer. The excellent axial to point chirality transfer is a result of the large ter/-butyl substituent forcing counterclockwise rotation (as viewed by the reader). 

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