Stereoselectivity asymmetric reactions, intramolecular

Dipolar cycloaddition reactions are of main interest in nitrile oxide chemistry. Recently, reviews and chapters in monographs appeared, which are devoted to individual aspects of these reactions. First of all, problems of asymmetric reactions of nitrile oxides (130, 131), including particular aspects, such as asymmetric metal-catalyzed 1,3-dipolar cycloaddition reactions (132, 133), development of new asymmetric reactions utilizing tartaric acid esters as chiral auxiliaries (134), and stereoselective intramolecular 1,3-dipolar cycloadditions (135) should be mentioned. Other problems considered are polymer-supported 1,3-dipolar cycloaddition reactions, important, in particular, for combinatorial chemistry... 

The asymmetric cyclisation of achiral olefinic organohthium reagents by a stereogenic alkah metal centre can be modulated by ( )-sparteine, which confers enantiofacial selectivity on the reaction such that the anionic cyclisation process discriminates between the enantiotopic faces of an unactivated C=C bond. Recently, modifications have been made to the well known hthium-ene cyclisation reaction whereby the subsequent expulsion of a thiophenoxide group yields a fused vinylcyclopropane. Moreover, allylic lithium oxyanion-induced reactivity and stereoselectivity in this intramolecular carbometallation has been demonstrated in the highly stereoselective synthesis of a natural bicyclo[3.1.0] hexane. ... 

A new noncarbohydrate-based enantioselective approach to (—)-swainsonine was developed in which the key step was an aqueous intramolecular asymmetric hetero-Diels-Alder reaction of an acylni-troso diene (Eq. 12.57).128 Under aqueous conditions there was significant enhancement of the trans stereoselectivity relative to the reaction under conventional nonaqueous conditions. 

Intramolecular C-H insertion reactions of metal carbenoids have been widely used for the stereoselective construction of substituted lactams, lactones, cyclopentanones, benzofurans, and benzopyrans. Several excellent reviews have been published covering the general aspects of intramolecular C-H insertion by metal carbenoids.46,47 62 71 99-104 The following section highlights the major advances made since 1994, especially in asymmetric intramolecular C-H insertion. 

In the asymmetric hydrogenation of the (R)-phenylglycine derivative (54) in the presence of an achiral catalyst the stereoselectivity was reported 89) to be low. The lactone (55) could subsequently be converted into (S)-aspartic acid 89). This reaction sequence is an example of the intramolecular transfer of chirality with subsequent disappearance of the original chiral center. 

METHOXYCARBONYL-1,1,6-TRIMETHYL-1,4,4a,5,6,7,8,8a-OCTAHYDRO-2,3-BENZOPYRONE, an intramolecular Diels-Alder reaction is responsible for the diastereoselectivity. The stereoselective 1,4-functionalization of 1,3-dienes is exemplified by a two-step process leading to cis- and trans-1-ACETOXY-4-(DICARBOMETHOXYMETHYL)-2-CYCLOHEXENE. The effectiveness of a silyl hydride in providing a means for erythro-directed reduction of a p-keto amide is applied in a route to ERYTHRO-1 -(3-HYDROXY-2-METHYL-3-PHENYL-PROPANOYLJPIPERIDINE. This is followed by an asymmetric synthesis based on a chiral bicyclic lactam leading to (R)-4-ETHYL-4-ALLYL-2-CYCLOHEXEN-1-ONE. The stereoselectivity with which acetoxy migration can operate to an adjacent radical center is reflected in the one-step reaction that gives rise to 1,3,4,6-TETRA-O-ACETYL-2-DEOXY-a-D-GLUCOPYRANOSE. 

Asymmetric intramolecular Wittig reaction. Trost and Curran2 have examined eight readily available optically active phosphines in a stereoselective synthesis of the ilikctone (2), a useful intermediate to several natural products. Of these, CAMP is dearly the most efficient phosphine for this purpose (equation I). 

Fig. 9. Nicolaou s asymmetric total synthesis stereoselective intramolecular Diels-Alder reaction.

In summary, the C-H insertion chemistry of rhodium carbenoids is a very powerful method for transformation of C-H bonds. Highly regioselective and stereoselective reactions are possible and several classes of chiral catalyst are capable of very high asymmetric induction. The chemoselectivity in this chemistry is exceptional, as illustrated by the numerous intermolecular and intramolecular reactions described in this overview. Most notably, this chemistry offers new and practical strategies for enantioselective synthesis of a variety of natural products and pharmaceutical agents. 

---