Double diastereofacial selectivity

To achieve high stereoselectivity applicable to any aldehyde in the cyclocondensation reaction the use of double diastereofacial selectivity has been investigated. These studies revealed an interesting relationship between the chiral catalyst used in the reaction and the chiral auxiliary. Contrary to the notion that the selectivity of a chiral diene and chiral dienophile are enhanced only in a matched pair, the interactivity of a chiral catalyst with a chiral diene where the two individual components have an opposite facial preference seems to give a high degree of asymmetric induction in the cyclocondensation reaction. ... 

A variety of methods are now available to control the relative and absolute stereochemistry of the cyclocondensation reaction of activated dienes with aldehydes. Chiral aldehydes that posses a high degree of diastereofacial selectivity with a variety of dienes can be used and the stereoselectivity controlled by the choice of diene, aldehyde and catalyst. Chiral dienes in combination with chiral catalysts can also be used in an unusual process of double diastereofacial selectivity. The resulting adducts can be purified and eliminated to give optically pure dihydropyrones. The chiral auxiliary can be isolated and reused if... 

Optical induction in the Euihfch-catalyzed reaction 2.5.4.22 Optical induction using a chiral aluminum catalyst 2.5.423 Double diastereofacial selectivity... 

Evidently, the intrinsic diastereofacial selectivity preference of 13 is too great for the chiral 2-butenylboronate to dominate the stereochemical course of this reaction. A second unsuccessful attempt at a demanding case of mismatched double diastereoselection has been reported by Burgess87. 

By way of comparison, the mismatched double asymmetric reaction of (5)-2-methylbu-tanal and E)- -methoxy-2-butenylboronate (5)-4 exhibits much greater selectivity. Dia-stereomers 9 (ca. 95%) and 7 (ca. 5%) are the only observed products, indicating that the diastereofacial selectivity of the 9/10 pair is >95 5. Here again, the small amount of 7 that was obtained (5 %) probably derives from the reaction of (S)-2-methylbutanal and the enantiomeric reagent (/ )-4, since (S)-4 is not enantiomerically pure (ca. 90% ee). 

The greater diastereofacial selectivity of 4 is also evident in the attempted mismatched double asymmetric reactions of 3 and 4 with aldehydes 11 and 15. which have greater intrinsic diastereofacial preferences than (S)-2-methylbutanal. 

The diastereofacial selectivity of this asymmetric [3C+2S] process is explained following a model similar to that described in Sect. 2.6.4.4 for the reaction of chiral alkenylcarbene complexes and 1,3-dienes. Thus, the proposed mechanism that explains the stereochemistry observed assumes a [4+2] cycloaddition reaction between the chromadiene system and the C=N double bond of the imine. The necessary s-cis conformation of the complex makes the imine... 

Murray and colleagues199 developed some 2,5-diketopiperazines as new chiral auxiliaries and examined their asymmetric induction in the Diels-Alder reactions of their A-acryloyl derivatives with several dienes. Some of their results with dienophile 320 have been summarized in Table 19 (equation 89). When the benzyl group on 320 was substituted by an isopropyl or /-butyl group, the diastereofacial selectivity dropped dramatically. It was proposed that tv-tt stacking between the phenyl group and the electron-poor double bond provided a more selective shielding of one face of the double bond in this special case. 

A and B are applicable to systems with R6 = H, whereas C has to be considered for cw-substi-tuted double bonds (R° 4= H)40. By far the most efficient and reliable alternative is depicted by model C40, which in many cases leads to high diastereofacial selectivities (>9 1). Therefore, it is necessary to introduce a dummy substituent, like trimethylsilyl or tributylstannyl, into the R6 position, which may be removed by protonolysis after the addition40. 

Based on the presumption that the enamine double bond would possess an ( -configuration, the diastereofacial selectivity can be explained by comparing two potential transition states A and B5 (Scheme 2.3e). Thus, a //-diol products... 

A double diastereotopic differentiation strategy on a phosphonoacetate template has been described. The approach utilizes Rh2(OAc)4-catalysed intramolecular cyclopropanation (ICP) employing the (R)-pantolactone auxiliary in the ester functionality of the phosphonoacetate (328).The olefinic diastereofacial selectivity is governed by inherent electronic and steric interactions in the reacting carbene intermediate, while the group selectivity is dictated by the chiral auxiliary. This approach is an effective method to access bicyclic P-chiral phos-phonates (329) (Scheme 87). ... 

Danishefsky, S J, Larson, E, Springer, J P, A totally synthetic route to lincosamine some observations on the diastereofacial selectivity of electrophilic reactions on the double bonds of various 5-(l-alkenyl)arabinopyranosides, J. Am. Chem. Soc., 107, 1274-1280, 1985. 

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