Acyclic a,p-unsaturated ketones

Subsequently, List reported that although the method described above was not applicable to the reduction of a,P-unsaturated ketones, use of a chiral amine in conjunction with a chiral anion provided an efficient and effective procedure for the reduction of these challenging substrates [210]. Transfer hydrogenation of a series of cyclic and acyclic a,P-unsaturated ketones with Hantzsch ester 119 could be achieved in the presence of 5 mol% of valine tert-butyl ester phosphonate salt 155 with outstanding levels of enantiomeric control (Scheme 64). A simple mechanistic model explains the sense of asymmetric induction within these transformations aUowing for reliable prediction of the reaction outcome. It should also be noted that matched chirality in the anion and amine is necessary to achieve high levels of asymmetric induction. 

In related work, Sasai developed several bifunctional BINOL-derived catalysts for the aza-Morita-Baylis-Hillman (aza-MBH) reaction [111]. In early studies, careful optimization of the catalyst structure regarding the location of the Lewis base unit revealed 41 as an optimal catalyst for the aza-MBH reaction between acyclic a,P-unsaturated ketones and N-tosyl imines. Systematic protection or modification of each basic and acidic moiety of 41 revealed that all four heterofunctionalities were necessary to maintain both chemical and optical yields. As seen in Scheme 5.58, MO calculations suggest that one hydroxyl groups forms a... 

Lygo and Wainwright recently reported a detailed study of the asymmetric phase-transfer mediated epoxidation of a variety of acyclic a,P-unsaturated ketones of the chalcone type. The third-generation cinchona-derived quats (8c and 7c), related to those discussed earlier in the alkylation section and Scheme 10.4, gave the best inductions (89% ee, 88 to 89, Scheme 10.13 and 86% ee for the pseudoenantiomeric catalyst 7c to give, as product, the enantiomer of 89). 

The reduction of a,p-unsaturated ketones is equally fast and remarkably selective for 1,2-addition of the silane. A variety of both cyclic and acyclic a,p-unsaturated ketones were reduced with diphenylsilane under the standard conditions with yields ranging from 66-99% for 1,2-addition. Cyclic enones were reduced with a higher degree of regioselectivity than the acyclic enone, mesityl oxide. 

Node, M., Nishide, K., Shigeta, Y., Shiraki, H., Obata, K. A Novel Tandem Michael Addition/Meerwein-Ponndorf-Verley Reduction Asymmetric Reduction of Acyclic a,P-Unsaturated Ketones Using A Chiral Mercapto Alcohol. J. Am. Chem. Soc. 2000, 122,1927-1936. 

The Corey-Bakshi-Shibata reduction (CBS reduction) is a highly enantioselective method for arylketones, diaryl ketones, and dialkylketones. In addition, cyclic a,p-unsaturated ketones, acyclic a,p-unsaturated ketones, and a,p-ynones are reduced enantioselectively in a 1,2-fashion. The high enantioselective nature of this reduction relies on the chiral oxazaborolidine catalyst, shown in the reaction scheme, in the presence of borane or a dialkylborane. Reviews (a) Singh, V. K. Synthesis 1992, 605-617. (b) Deloux, L. Srebnik M. Chem. Rev. 1993,93,163-1. (c) Corey, E. J. Helal, C. J. Angew. Chem. Int. Ed. 1998, 37. 1986-2012. 

The reaction was efficiently catalyzed by a rhodium complex generated in situ by mixing Rh(acac)(CH2=CH2)2 with 1 equiv of (S)-binap in an aqueous solvent at 100 C. It was interesting that the enantioselectivity was kept constant at the reaction temperature ranging between 40-120 C in the addition to 2-cyclohexenone. High enantioselectivity exceeding 90%ee were readily achieved for both cyclic and acyclic a,P-unsaturated ketones with variety of aryl- and alkenylboronic acids. 

Development of highly enantioselective oxazaborolidinone catalysts for the reactions of acyclic a,p-unsaturated ketones 07SL1823. 

Aznar, et al. reported a proline-catalyzed imino-Diels-Alder reactions of acyclic a,p-unsaturated ketones 96 with imines 92 for the synthesis of mc50-2,5-diaryl-4-piperidones 98, Scheme 3.35 [50], The 2-amino-1,3-butadiene was generated in situ by the reaction of a,p-unsaturated ketones 96 with L-proline, followed by Diels-Alder cycloaddition with imine 92 to provide tetrahydropyridine adduct which was then hydrolyzed to the 4-piperidone 98. 

Michael-type additions to alkenylmetallics have serious defects because of the inapplicability due to readily-polymerizability of acyclic a,p-unsaturated ketones [17], Organoboranes, on the other hand, give good results, even for acyclic enones [18], but there is no direct and general method for the synthesis of p,p-disubstituted alkenylboranes. However, cross-coupling reaction [1-4] between 6-halo-y,6-unsaturated ketones and organometallics do afford the 6,6-disubstituted-Y,6-unsaturated ketones. 

Acyclic a,P-unsaturated ketone 34 on Norrish type II reactions gives both normal product 35 and a by-product 36 due to resonance hybrid of the diradical intermediate [20]. 

Kobayashi et al. disclosed the effectiveness of lanthanides triflates as Lewis acid fear Mukaiyama-Michael reactions of a,p-unsaturated ketones and enol silyl ethers [llj. Virtually all of the lanthanide triflates except for Ce(OTf)3 and Tb(OTf)3 worked well and could be reused. By using 10mol% of Yb(OTf)3, the reaction proceeded smoothly with both cyclic and acyclic a,p-unsaturated ketones to afford 1,5-dicarbonyl compounds in high yield (Scheme 13.3). Remarkably, the recovered catalyst exhibited comparable catalytic performance in the second runs. 

The great advance in this area is the discovery that chiral organoboron dichlorides bearing a naphthalene moiety catalyze the enantioselective Diels-Alder reactions of a,p-unsaturated esters and cyclopentadiene to produce up to 99.5% ee (Scheme 23.47). A molecular complex between methyl crotononate and the catalyst was isolated. Using the same catalyst, Diels-Alder reactions between simple acyclic a,p-unsaturated ketones and a,P-unsaturated acid chlorides produce 83% and 92% ee, respectively. ... 

Most known chiral secondary-amine catalysts are effective only for less sterically hindered substrates such as a,p-unsaturated aldehydes. Asymmetric Diels-Alder reactions of acyclic a,p-unsaturated ketones represent a formidable challenge in this area. In 2002, MacMillan and coworkers accomplished the first general enanti-oselective Diels-Alder reactions of ketones by using chiral amine 26 [16]. As shown... 

Zhao and co workers [54] developed simply primary-secondary diamine catalysts derived from primary amino acids. This type of catalysts such as 105 was found to catalyze the asymmetric Michael addition of malonates to acyclic a,p-unsaturated ketones with good activity and excellent enantioselectivity (Scheme 5.27). Liang and coworkers designed a new primary amine catalyst combining two privileged skeletons, cinchona and cylohexanediamine [55], The obtained optimal catalysts 107 and 110 were applicable to the Michael additions reactions of malonate or nitroalkanes to a,p-unsaturated ketones. The reactions worked well with both cyclic and acyclic enones (Scheme 5.28). 

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