Keto allylic esters

Enone formation-aromatization has been used for the synthesis of 7-hydro-xyalkavinone (716)[456]. The isotlavone 717 was prepared by the elimina-tion[457]. The unsaturated 5-keto allyl esters 718 and 719, obtained in two steps from myreene. were subjected to enone formation. The reaction can be carried out even at room temperature using dinitriles such as adiponitrile (720) or 1,6-dicyanohexane as a solvent and a weak ligand to give the pseudo-ionone isomers 721 and 722 without giving an allylated product(458]. 

In 1940 Carroll reported the rearrangement of P-keto allyl esters (49) followed by decarboxylation to yield y,5-unsaturated ketones (53) via a [3,3]-sigmatropic (Claisen) rearrangement (Scheme 4.13) [31]. The reaction has found limited scope in organic synthesis due to the harsh conditions required (130-220 °C) to induce the rearrangement. 

The enantioselective version developed by Stoltz was optimised using ()-keto allyl ester 102. As in the report by Tsuji, Pd(OAc)2 was used as the Pd source in the presence of (5)-r-BuPHOX with formic acid in the presence of EtaN, however, this only led to an ee of 7 %. An improvement to 24 % was observed in the absence of EtaN and, upon the addition of molecular sieves to sequester the small amounts of water present in commercially available formic acid, the ee increased drastically to 72 %. Switching the molecular sieves for 3 A and the solvent from THF to 1,4-dioxane and optimisation of the quantity of formic acid and the molecular sieves further increased the ee to 94 % (Scheme 4.29). 

The optimised conditions were then applied to a range of cyclic a-alkyl and a-benzyl substituted P-keto allyl esters to generate the corresponding a-tertiary ketones in good yields and excellent enantioselectivities. Interestingly the fused aromatic substrates such as tetralone 102 gave the opposite sense of stereoinduction in the resulting tertiary product (105), compared to the monocyclic compounds such... 

Synthesis of AryUead Triacetates for the C-Arylation of P-Keto Allyl Esters... 

The synthesis of a series of a-aryl-P-keto allyl esters was accomplished by first preparing cyclopentanone- and cyclohexanone-derived P-keto allyl esters 3 and 4 (Scheme 6.1). This was achieved via Dieckmann condensation of commercially available diallyl adipate using NaH as the base to generate cyclopentanone P-keto allyl ester 3 in 73 % yield. Similarly, diallyl pimelate, prepared by transesterification... 

Scheme 6.1 Synthesis of cyclopentanone and cyclohexanone p-keto allyl esters...

The next step was to generate a series of a-aryl-P-keto allyl esters from the cyclopentanone and cyclohexanone P-keto-allyl esters. This could be achieved by the use of aryUead triacetates under relatively mild conditions of 40 °C in the presence of pyridine. These reagents have shown a remarkable abihty for the a-arylation of P-keto esters, particularly impressive is their abihty to introduce ste-rically bulky aryl groups generating a quaternary centre in very high yields (see Sect. 4.7.2). 

A total of 11 aryllead triacetates were prepared according to previously reported methods. [1] We chose a number of sterically demanding aryl groups as this was hitherto important to achieve reasonable levels of enantioinduction. These were successfully used in the arylation of the cyclopentanone and cyclohexanone P-keto allyl esters in moderate to excellent yields, with the exception of the... 

Step by Pb-mediated a-arylation of a P-keto allyl ester. In particular this allows the insertion of bulky aryl groups where the new stereocentre is generated. Furthermore, the conditions developed for the decarboxylative asymmetric protonation reaction achieved good levels of enantioselectivity for mono- and di-oitho substituted aryl groups. 

General Procedure for the Preparation of o-Aryl-p-keto Allyl Esters (5 and 6)... 

The title compound was prepared according to the general procedure using P-keto allyl ester (19) (291 mg, 1.48 mmol) and 2,4,6-trimethoxyphenyIlead triacetate (979 mg, 1.78 mmol) to yield the product as a white solid (439 mg, 82 %). 

Pd(OAc)2 (3.4 mg, 0.015 mmol) and dppe (7.5 mg, 0.019 mmol) were added to a flame dried Schlenk flask (10 mL) and 1,4-dioxane (1.5 mL) was added. The suspension was stirred at 40 °C for 90 min and formic acid (34 pL, 0.90 mmol) was added followed immediately by a-aiyl-P-keto allyl ester (0.15 mmol) in 1,4-dioxane (1.5 mL) from a flame dried round bottom flask (10 mL, 2-neck). The reaction mixture was stirred at 40 °C for 10 h, cooled to room temperature and filtered through a plug of Celite and washed with Et20. The solvent was removed in vacuo and the resulting residue was purified by silica gel column chromatography (pentane/Et20). 

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