Homo Diels-Alder reaction enantioselective

Dipolar cydoadditions are one of the most useful synthetic methods to make stereochemically defined five-membered heterocydes. Although a variety of dia-stereoselective 1,3-dipolar cydoadditions have been well developed, enantioselec-tive versions are still limited [29]. Nitrones are important 1,3-dipoles that have been the target of catalyzed enantioselective reactions [66]. Three different approaches to catalyzed enantioselective reactions have been taken (1) activation of electron-defident alkenes by a chiral Lewis acid [23-26, 32-34, 67], (2) activation of nitrones in the reaction with ketene acetals [30, 31], and (3) coordination of both nitrones and allylic alcohols on a chiral catalyst [20]. Among these approaches, the dipole/HOMO-controlled reactions of electron-deficient alkenes are especially promising because a variety of combinations between chiral Lewis acids and electron-deficient alkenes have been well investigated in the study of catalyzed enantioselective Diels-Alder reactions. Enantioselectivities in catalyzed nitrone cydoadditions sometimes exceed 90% ee, but the efficiency of catalytic loading remains insufficient. 

Brunner H. Enantioselective Catalysis With Transition Metal Componnds. Right or Left - This Is the Qnestion Adv. Chem. Ser. 1992 230 143-152 Keywords homo-Diels-Alder reaction of norbornadiene... 

Replacement of bis(l,2-diphenylphosphino)ethane by chiral phosphanes such as (— )-(25, 3 5)-bis(diphenylphosphino)butane or (- -)-(/ )- ,2-bis(diphenylphosphino)propane allows a highly enantioselective cobalt-catalyzed homo-Diels-Alder reaction (maximum 91% ee) between norbornadiene and monosubstituted alkynes. Similarly, the reaction of norbornadiene with phenylacetylene in the presence of catalytic amounts of tris(acetylacetonato)cobalt and (-l-)-bicyclo[2.2.1]hept-5-ene-2,3-diylbis(diphenylphosphane) leads quantitatively to the homo-Diels-Alder adduct with an ee of 98.4%. ... 

More recently, Buono and Pardigon showed that the catalytic system used by Cheng and co-workers, [Col2(PPh3)2]/Zn, replacing PPhj with an amino acid based chiral phosphine (Fig. 14), gives a highly enantioselective homo Diels-Alder reaction (with phenylacetylene and 1-hexyne, up to 97% ee is achieved). 

We have investigated the scope of the cobalt- and nickel-catalyzed [2 + 2 + 2] (homo Diels-Alder) and [2 + 2] cycloaddition reactions with norbomadienes. Excellent chemo-, regio- and stereoselectivities and high levels of enantioselectivities are achieved. 

The first amine-catalyzed Diels-Alder reaction of a,(i-unsaturated carbonyl compounds as dienes involving in situ enamine activation with chiral amine 29 through raising the diene HOMO energy was accomplished by Barbas and coworkers in 2002 with moderate enantioselectivity (up to 38% ee) [17a]. In 2007, Cordova and coworkers described chiral amine 29 catalyzed enantioselective Diels-Alder reactions between a,P-unsaturated cyclic ketones and nitroolefins with up to 86% ee [17b]. Two years later, Xu and coworkers successfully disclosed a highly efficient enantioselective Diels-Alder reaction of cyclohexenones 31 with aromatic nitroolefins 32 using amine 30 as catalyst in seawater or brine to give products 32 with excellent enantioselectivities (Scheme 38.10) [18a]. Notably, sea water and brine... 

Inomata100 utilized a tandem retro-Diels-Alder-ene reaction for an enantioselective total synthesis of (+)-methyl jasmonate (Scheme 41). The TMS group on the alkene was essential to the efficiency of the reaction, by producing a higher energy level of the HOMO for the ene reaction. 

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