Stereodivergent approach

A stereodivergent approach to 2,5-disubstituted dihydrofurans that makes use of a stereoselective Ir-catalyzed allylic etherification of Cu-alkoxides followed by an RCM has been reported by Hartwig and Shu (Scheme 39). Due to the catalyst-controlled stereoselectivity in the allylic etherification step, both the cis- and the /ra r-epimer are made accessible depending on which enantiomer of the phosphoramidite ligand is employed <2004AGE4794>. 

An intriguing stereodivergent approach to both enantiomers of slaframine, devised by Carretero and Gdmez Arrayds, commenced with the reductive amination of (/J)-glyceraldehyde acetonide 50 with the diethyl acetal of 4-aminobutanal (Scheme 7) (48). The secondary amine product 51 was transformed in three steps into a 1 1 diastereomeric mixture of a, 3-un5atuiated y-hydroxysulfones 52,... 

The epimeric (+)-a-allokainic acid was constructed by the unsaturated imide/ alkyne alkylative coupling of 9 with trimethylaluminum in 73% yield and 97 3 diastereoselectivity (Scheme 8.11) [33]. This was followed by silyl to carbonate protecting group transposition, stereoselective aUylic reduction, and removal of protecting groups to afford (+)-a-allokainic acid. The complementary nature of these two stereodivergent approaches allowed access to both epimeric natural products. 

Aoyagi Y, Jain RP, Williams RM (2001) Stereocontrolled Asymmetric Synthesis of o -Hydroxy-/ -amino Acids. A Stereodivergent Approach. J Am Chem Soc 123 3472... 

It is also worth mentioning that the stereochemical outcome of reactions A and B can be reversed by forcing the chiral aldehydes to adopt a different reacting conformation. Thus, different stereoisomers arising from stereodivergent reaction courses can be obtained from the same substrate, greatly expanding the applicability of this approach. 

Liebeskind s second-generation approach to the stereocontrolled synthesis of 2,3,6-trisubstituted piperidines was based on the use of a range of molybdenum-containing scaffolds that were not only general and efficient precursors for the regjo- and stereodivergent preparation of the targets, but could also be obtained in enantiomerically pure form. This impressive... 

The strength of the Paterson approach is clearly due to the fact that this method is highly efficient for aldol additions of ketones with a chiral skeleton to chiral or achiral aldehydes, in the course of which the diisopinocampheylborane eno-lates exhibit distinct stereocontrol. An illustrative example thereof is shown in Scheme 4.67 by the stereodivergent aldol addition of enantiomerically pure ketone... 

In a stereodivergent and highly stereoselective approach (Scheme 31), piperidine 122 was transformed into either diol 149 (with a nitrogen atom masked as trifluoroacetate during the catal3rtic osmylation), or its diastereoisomer 148 (directing role of the nitrogen atom in the formation of osmate 146). ... 

Kumar V, Ramesh NG. A Glycal approach towards an efficient and stereodivergent synthesis of polyhydroxypyrroli-dines. Tetrahedron 2006 62(8) 1877 1885. 

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