Memory of Chirality—A New Principle in Enolate Chemistry

Abstract

We discuss a new principle, memory of chirality, which was recently introduced in the field of asymmetric synthesis. Memory of chirality is a phenomenon in which the chirality of the starting material is preserved in a reactive intermediate for a limited time. Examples are discussed, including the enantioselective alkylation of a ketone and amino acid derivatives.

Benzylic Metallation of Thiobenzamides and Thionaphthamides

“…Achievements with axial chirality have been spectacular [20,21] for binaphthyl derivatives (Binol, Binap etc.). Very recently, another molecule type, aromatic amides or esters, has been explored by some groups, those of Fuji, [22,23] Clayden, [7,24Ϫ28] Curran, [29Ϫ31] Simpkins [32,33] and Taguchi. [34,35] To the best of our knowledge, no report deals with the use of thioamides for atroposelective synthesis.…”

Principles, Concepts and Strategies of Stereoselective Synthesis

“…39,40 The conversion from the R-to the S-enantiomer in the phenylalanine molecule would require the breaking of a bond followed by the formation of new bond; therefore, it possesses a static (absolute) chirality. In contrast, the conversion of b-phenylpropionic acid into its mirror image can be possible just by bond rotation.…”

“…10 Fuji and Kawabata also proposed a term dynamic chirality because the chiral properties of such molecules are time and temperature dependent. 39,40 For example, 2,2'-dimethylbiphenyl possesses a dynamic chirality because rotation around a CÀC single bond is restricted (rotation barrier ¼ 18 kcal/mol).…”

“…Later the same authors generalized their definition of MOC as "the chirality of the starting material is preserved in a reactive intermediate for a limited time". 39 Matrumura et al defined the memory of chirality as a phenomenon in which "the chirality of a starting material having a chiral sp 3 -carbon is preserved in the reaction product even though the reaction proceeds at the chiral carbon as a reaction center through reactive intermediates such as carbanions, singlet monoradicals, biradicals, or carbenium ions". 42 Carlier et al 43 in their review described this process as follows: "[A] 'memory of chirality' reaction can be defined as a formal substitution at an sp 3 stereogenic center that proceeds stereospecifically, even though the reaction proceeds by trigonalization of that center, and despite the fact that no other permanently chiral elements are present in the system.…”

Diastereo- and Enantioselective Synthesis of Pyrrolo[1,4]benzodiazepines through Decarboxylative Photocyclization

“…The lifetime of these intermediates and their conformational flexibilty is decisive for the degree of stereoselectivity. Besides reactions with carbanions, [1] monoradicals, [2] or carbenium ions, [3] combination reactions of diradicals are promising due to the very low (if present at all) activation barriers. This approach was described recently by Giese and co-workers for the cyclization of photochemically generated 1,5-diradicals with singlet multiplicity.…”