In memoriam A. I. Meyers 3 ), who paved the way for the use of heterocycles in stereoselective organic synthesis 4 )Reaction of 2-phenylacetaldehyde with the Me 3 Si ether of diphenyl-prolinol, with removal of H 2 O, gives a crystalline enamine (1). The HBF 4 salts of the MePh 2 Si ether of diphenyl-prolinol and of 2-(tertbutyl)-3-methyl-and 5-benzyl-2,2,3-trimethyl-1,3-imidazolidin-4-one react with cinnamaldehyde to give crystalline iminium salts 2, 3, and 4. Single crystals of the enamine and of two iminium salts, 2 and 3, were subjected to X-ray structure analysis (Figs. 1, 2, and 6), and a 2D-NMR spectrum of the third iminium salt was recorded (Fig. 7). The crystal and NMR structures confirm the commonly accepted, general structures of the two types of reactive intermediates in organocatalysis with the five-membered heterocycles, i.e., D, E (Scheme 2). Fine details of the crystal structures are discussed in view of the observed stereoselectivities of the corresponding reactions with electrophiles and nucleophiles. The structures 1 and 2 are compared with those of other diphenyl-prolinol derivatives (from the Cambridge File CSD; Table 1) and discussed in connection with other reagents and ligands, containing geminal diaryl groups and being used in enantioselective synthesis (Fig. 4). The iminium ions 3 and 4 are compared with N-acylated imidazolidinones F and G (Figs. 9, 12, and 13, and Table 3), and common structural aspects such as minimalization of 1,5-repulsion (the A 1,3 -effect), are discussed. The crystal structures of the simple diphenyl-prolinol · HBF 4 salt ( Fig. 3) and of Boc-and benzoyl-(tert-butyl)methyl-imidazolidinone (Boc-BMI and Bz-BMI, resp.; Figs. 10 and 11) are also reported. Finally, the crystal structures are compared with previously published theoretical structures, which were obtained from high-level-oftheory DFT calculations (Figs. 5 and 8, and Table 2). Delicate details including pyramidalization of trigonal N-atoms, distortions around iminium C¼N bonds, shielding of diastereotopic faces, and the pinteraction between a benzene ring and a Me group match so well with, and were actually predicting the experimental results that the question may seem appropriate, whether one will soon start considering to carry out such calculations before going to the laboratory for experimental optimizations. 2000 5 ) In this expanding field of organic chemistry, we have to refer to selected reviews and a few seminal original articles [1], and the enumeration of reactions given here cannot be complete. 6 ) Besides proline itself, derivatives such as a-methyl-proline, proline amides, a tetrazole [1r], sulfonylimides, and (aminomethyl)-pyrrolidines [1m] have been used as catalysts. 7 ) See also the use of chiral H-bond donors [1j], of Brønsted acids [1t], and of heterocyclic carbenes [1p] as catalysts. 8 ) See summary of a 1990 review article entitled Organic Synthesis -Where now? [2]. 9 ) Cf. the title In the Golden Age of Organocatalysis [1c]; Asymmetric Organocatalysis: From Infancy to Adolescence [1u]...
