Diastereoselectivity hydrogen bonding

Scheldt and Chan have shown that NHC promoted homoenolate formation and addition to azomethine imines 37 generates pyridazinones 41 with high diastereoselectivity, via a proposed highly organised transition state 40 due to a key hydrogen bonding interaction (Scheme 12.6) [12]. 

Mandelate and lactate esters have been found to generate diastereoselectivity in reactions of hydroxy-substituted quinodimethanes generated by thermolysis of benzo-cyclobutenols.88 The reactions are thought to proceed by an exo TS with a crucial hydrogen bond between the hydroxy group and a dienophile carbonyl. The phenyl (or methyl in the case of lactate) group promotes facial selectivity. 

Table 21.5 Diastereoselective hydrogenation of alcohols with exocyclic double bond. 

Table 21.6 Diastereoselective hydrogenation of double bond in cyclic esters and carboxylic acids. 

The configuration of the product in diastereoselective hydrogenation -whether 1,2-syn or 1,2-anti - is related to the substitution pattern of the starting alkene. The allyl alcohol with a 1,1-disubstituted olefin unit affords the antiproduct, while the syn-product is formed from the allyl alcohol with a trisubsti-tuted olefmic bond (Table 21.8, entries 6-9). The complementarity in diastereoselective hydrogenation of di- and tri-substituted olefins may be rationalized based on the conformation analysis of the intermediary complex (Scheme 21.1)... 

During the course of the development of a new technical synthesis at Lonza for biotin (a water-soluble vitamin), the Rh-Josiphos-catalyzed diastereoselective hydrogenation of a tetrasubstituted C=C bond turned out to be a key step [40, 42, 81] (Fig. 37.19). 

In isopropyl alcohol, the erythro-isova t is formed predominantly. An increase in the polarity of the solvents results in a shift of the diastereoselectivity to the f/ r< o-isomcr and in methanol this becomes the main product. This example offers another possible influence of the solvent. An explanation of the determined diastereoselectivies can be different conformations preferred in the various solvents. In isopropyl alcohol the intramolecular hydrogen bonds can stabilize the conformation and the attack of hydrogen can occur only with the erythro-isovaer formation (Scheme 14.13). In a polar solvent, this possibility is much diminished and therefore the isomer is preferred. 

An important example of heterogeneous diastereoselective synthesis by catalytic way is the synthesis of prostaglandines (a family of compounds having the 20-carbon skeleton of the prostanoic acid) (Scheme 14.14). Naturally, these molecules are biosynthesized via a cyclooxygenase enzyme system that is widely distributed in mammalian tissues. Many of the synthetic routes [272] involve the diastereoselective hydrogenation of a carbonylic bond having a C=C double bond... 

Examples of the Bronsted-acid catalysts and hydrogen-bond catalysts are shown in Figure 2.1. We have recently reported the Mannich-type reaction of ketene silyl acetals with aldimines derived from aromatic aldehyde catalyzed by chiral phosphoric acid 7 (Figure 2.2, Scheme 2.6) [12]. The corresponding [5-amino esters were obtained with high syn-diastereoselectivities and excellent enantioselectivities. 

Urea 32, the bis-(mono-trifluoromethyl)phenyl derivative of urea catalyst 16 [178], was reported to operate as double hydrogen-bonding organocatalyst in the diastereoselective synthesis of y-butenolide products substituted at the y-position... 

Electron-poor allylic alcohols, studied by Adam and coworkers, were found to react r/treo-selectively, regardless of whether the hydroxy functionality is free or masked by alkyl or silyl groups (Scheme 35). This diastereoselectivity, for which the nature of the solvent had no significant influence, was attributed to stereoelectronic effects rather than intramolecular hydrogen bonding or steric strain. 

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