Intramolecular Asymmetric Allylations

Enamines derived from ketones are allylated[79]. The intramolecular asymmetric allylation (chirality transfer) of cyclohexanone via its 5-proline ally ester enamine 120 proceeds to give o-allylcyclohexanone (121) with 98% ee[80,8l]. Low ee was observed in intermolecular allylation. Similarly, the asymmetric allylation of imines and hydrazones of aldehydes and ketones has been carried out[82]. 

Park et al.102 demonstrated an interesting intramolecular asymmetric allylation of imine based on a substrate-controlled mode. 

Scheme 3. Pd-catalyzed intramolecular asymmetric allylic alkylation in Genet s synthesis of chanoclavine I (1994).

Scheme 9.21 Sequential intermolecular and intramolecular asymmetric allylic aminations.

In an enantioselective route to the F-ring of halichondrin B, the diastereoselection with a C2-symmetric diol in intramolecular asymmetric allylic alkylation (AAA) reactions has been investigated (Equation 74) <20020L3411>. 

Continuing with palladium chemistiy, Trost proposed a new asymmetric synthesis of anatoxin-a (Trost and Oslob, 1999) and the crucial step was the introduction of chirality by a catalytic process involving an intramolecular asymmetric allylic alkylation (Trost 2004) of the intermediate ( )-29 affording (+)-31 (Scheme 7.7). This step was catalyzed by palladium in presence of a chiral phosphine ligand. 

On the other hand, unsaturated aldehydes and ketones were obtained using allylic alcohols as alkene components [68]. Similarly, allyl f-butyldimethylsilyl ether and N-allylamides gave silyl enol ethers [69] and enamides [70], respectively. The ruthenium-catalyzed alkene-alkyne coupling was successfully combined with the palladium-catalyzed intramolecular asymmetric allylic alkylation [71] to provide a novel one-pot heterocyclization method [72]. 

Intramolecular asymmetric allylic substitution reactions have been applied to the synthesis of optically active cyclic compounds. The high efficiency of the dihydroxylated ferrocenylphosphine 8b has been shown in the cyclization of 2-butenylene dicarbamates 52 to form optically active 4-vinyl-2-oxazolidones 53, which are... 

A significant study of the synthesis of chiral chromans by the Pd-catalysed intramolecular asymmetric allylic alkylation of readily available phenol allyl carbonates has established the optimum conditions for this highly efficient method and demonstrated its value by the total syntheses of (+)-clusifoliol and (-)-siccanin (Scheme 6) <04JA11966>. A biomimetic enantioselective synthesis of (-)-siccanin also features this approach to the chroman moiety <04JA12565>. 

Table 6.14 Pd-catal) ed intramolecular asymmetric allylic alkylation reaction reported by Bandini and Umani-Ronchi.

Eneouraged hy Bandini s pioneering studies, You and co-workers introduced indolyl carbonates 180 into Ir-catalyzed intramolecular asymmetric allylic alkylation reactions. Interestingly, spiroindolenine derivatives 181 are obtained in 50-98% yields with up to >99/1 dr and 97% ee (Scheme 6.83). Chiral phosphoramidite ligand (/ ,/ a)-170d (Me-THQphos), newly developed by the You group, was responsible for excellent reactivity, diastereo- and enantioselectivity of this process. 

Scheme 6.83 Ir-catalyzed intramolecular asymmetric allylic alkylation reaction of indol-3-yl carbonates 180 reported by You.

Apart from reports on Ir-catalyzed intramolecular asymmetric allylic alkylation of substituted indoles with the linker attached on the C3 position,... 

Pham, P. V., Ashton, K., MacMillan, D. W. C. (2011). The intramolecular asymmetric allylation of aldehydes via organo-SOMO catalysis a novel approach to ring construction. Chemical Science, 2, 1470-1473. 

Scheme 39.6 Influence of olefin geometry on the selectivity of intramolecular asymmetric allylation under SOMO conditions.

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