Diastereoselectivity conversion

Among early and group III transition metals, the yttrocene catalysts have been studied in greatest detail. However, related metallocenes show great promise as catalysts for reductive cyclization. Neodymocene-catalyzed cyclization of 1,5- and 1,6-dienes 14a and 15a proceeds readily in the presence of silane to afford cyclopentanes 14b and 15b.37 Lutetocenes and samarocenes also catalyze silane-mediated cyclization of 1,5-diene 14a to cyclopentane 14b.38 39 In the case of the samarium-based metallocenes, the feasibility of borane-mediated cyclization has been established, as demonstrated by the highly diastereoselective conversion of phenyl-substituted diene 16a to cyclopentane 16b (Scheme ll).40... 

Intramolecular Mannich reactions have also been used in the synthesis of piperidines. An intramolecular Mannich reaction was applied as the key step in the synthesis of the piperidine A ring of cylindrospermopsin <07SL1446> and in the high yielding diastereoselective conversion of 3-amino acids to 2,6-yy -disubstituted piperidinones <07JOC10287>. 

In their synthesis of the cA-octahydronaphthalene nucleus 471 of superstolide A (Fig. 11 -39), Roush and co-workers demonstrated the use of Keck s original catalytic allylation procedure to effect the diastereoselective conversion of aldehyde 472 to the 1,3-vyn diol 473 (79% yield, selectivity=94 6) (Scheme 11-37) [313]. This transformation constitutes a mismatched reaction since the 3-anti diol is favored under substrate-controlled allylation (see Section 11.3 for a discussion of 1,3-stereo-induction) [93]. 

The reduction of iV-diphenylphosphinyl imines of substituted cycloalkanones with lithium tri-sw-butylborohydride (L-Selectride) provides highly diastereoselective conversions to protected axial primary amines in 83-96% yield17. The reduction of cyclohexylidene diphenylphos-phinyl imines with sodium borohydride is less diastereoselective17. 

All biotransformations mentioned above represent enantioselective reductions. In contrast, the reduction of the cyclic chiral acylsilane vac-225 with growing cells of Kloeckera corticis (ATCC 20109) into a 1 1 mixture of (S,R)-226 and (jR,S)-226 is an example of a diastereoselective conversion (yield of reduction product 95%, diaster-eomeric excess 90% de)19,283. 

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... 

The stereochemical course of the highly diastereoselective conversion of -keto y -hydroxy phosphine oxides (45) and related silylated derivatives (44) into cyclopropyl ketones, predominantly isomer (47), by treatment with Bu OK-Bu OH has been determined and used to synthetic advantage. ... 

The synthesis of the epoxide 48 is described in Scheme 15.15 in three steps, starting with a diastereoselective allylation of the lithium (Z)-enolate of 50 followed by a diastereoselective conversion of 51 to iodohydrin 52 via NIS-mediated cyclic iodoimidate formation and hydrolysis. Finally a base-mediated conversion of 52 to the epoxide 48 was accomplished, with all three steps giving excellent yields [29]. 

The hydroboration-oxidation of olefins is one example of this approach. The process involves a stereospecific ty -addition of H and OH across the olefin r-bond. This reaction sequence is regioselective with unsymmetri-cal olefins. The diastereoselective conversion of E-olefin 177 to 178, and the isomeric Z-olefin 179 to 180, illustrates this process. Note that this discussion applies to relative control of stereochemistry. Whereas use of an enantioselective hydroborating agent might afford 178 and 180 as single enantiomers (or enriched in one enantiomer), 177 would still provide 178 and the diastereomeric olefin (179) would provide the diastereomeric alcohol (180).20... 

Scheme 1.7 Diastereoselective methylation of 3-hydroxybutanoate 18 - an example of a diastereoselective conversion of a lithium enolate with a chiral skeleton.

However, diastereoselective transformations like this are not to be discussed within this monograph, as they do not fulfill the criteria of asymmetric synthesis, according to Marckwald s definition (in today s language) this would mean [...] those reactions, or sequences of reactions, which produce chiral nonracemic substances from achiral compounds with the intermediate use of chiral nonracemic materials, but excluding a separation operation [35]. Thus, diastereoselective conversions not included for that reason in this book are, for example, aldol additions, Mannich reactions, and Michael additions of enolates to ketones, imines, and cx,P-unsaturated carbonyl compounds, respectively, with any chiral skeleton. For such stereoselective enolate reactions that are not asymmetric syntheses, the reader is referred to the literature, which treated this topic in a comprehensive manner [36]. 

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