Diastereoselectivity products synthesis, domino reaction

Several other types of domino reactions have been employed in the synthesis of natural products. Diastereoselective conversion of allylic carbonate 173 into enone 174 was one key transformation in a total synthesis of (+)-3-isorauniticine 175 (Scheme 27).Treatment of allylic sulfonamide 173 with a palladium catalyst re-gioselectively forms a 7r-allylpalladium intermediate by carbonate displacement. Carbopalladation of the pendant alkene, carbonylation, a second intramolecular alkene insertion, and /3-hydride elimination delivers a 67 22 11 mixture of stereoisomers of which enone 174 is the major product (isolated in 45-53% yield). Carbopalladation products can also undergo anion capture reactions. For instance, during the synthesis... 

In contrast to the total synthesis of an NP, which often is a long, multistep, and time-consuming endeavor, generating NP-like compounds should follow easy and efficient synthesis routes to provide a large number of compounds. Domino reaction sequences can play a major role in providing relatively complex and NP-based compound collections. ChiraHty of the product is another important factor that determines the biological effect of a molecule. Therefore, enantioselective and diastereoselective domino reactions are of particular interest in this area. 

The synthesis of six-membered all-carbon rings have been extensively studied in the literature, mainly because of their importance as constituents in natural products and biologically relevant compounds. The first example of an enantioselective organocatalytic domino reaction with nitroalkenes to furnish cyclohexanes was disclosed by Takemoto and co-workers [38] in 2004. In this work, a domino Michael addition of 7,8-unsaturated-(3-ketoesters (58) to nitroalkenes (28) catalyzed by a bifunctional amino-thiourea (Takemoto s catalyst, XVIII) and 1,1,3,3-tetramethylguanidine (TMG) was reported with excellent results and diastereoselectivities (up to 71% yield, up to >99% ee) and was recently applied to the synthesis of (-)-epibatidine. 

The asynunetric organocatalytic triple cascade reaction for the synthesis of telrasu-bstituted cyclohexene carbaldehydes developed by Enders et al. (Scheme 1.30) [40] is a milestone of organocatalytic cascade reactions. This three-component domino reaction proceeds by way of a catalyzed Michael-Michael-aldol condensation sequence affording products in good to moderate yields (25 to 58%). Notably, four stereogenic centers are formed with high diastereoselectivity and complete enantioselectivity. 

In addition, we have also included chapters that are related to the type of process as organocatalysis, enantio- and diastereoselective reactions, and multicomponent reactions as well as domino processes under microwave irradiation, high pressure, and in water. Finally, two chapters that are more product oriented have been included on the synthesis of compound collections and the synthesis of natural products and analogs. 

Chiral oxazolidinones are the most popular auxiharies in the field of asymmetric synthesis. Chen and Sibi [76] employed this auxiliary for the domino asymmetric C-C/C-C single bond formation under convenient radical conditions (Scheme 5.51). During the reaction, the radical intermediates 240 was coordinated onto the Lewis acid Yb(OTf)3 at —78°C to form the desired s-cis conformation. Upon the treatment of this intermediate 240 by 2-methylallyl stannane, the product 241 was generated with a diastereoselectivity of >20 1. Similar radical conditions using a bromooxazolidinone imide source also resulted in allylated products with excellent diastereoselectivity (>50 1) and yield (>90%) even at room temperature. 

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