Stereoselective Mannich reaction of camphor titanium enolate

Trans-Stereoselectivity in the Reaction between Homophthalic Anhydride and Imines

“…Many mechanistic studies dealing with the TiCl 4 /amine system assume that the active enolates are neutral (CC−OTiCl 3 ) species and/or anionic (CC−OTiCl 4 − ) complexes . A recent paper has reported the presence of anionic titanium enolate complexes (CC−OTiCl 4 − ) in which the most stable form has significant biradical character.…”

Heterocycles 38. Biocatalytic Synthesis of New Heterocyclic Mannich Bases and Derivatives

“…-4-(2-phenylthiazol-4-yl) 89, 170.59, 167.23, 155.74, 140.24, 133.67, 130.05, 129.94, 129.29, 128.97, 128.43, 126.52, 116.90, 51.62, 45.81, 30.28, 23.60 02, 170.69, 167.56, 155.65, 138.78, 133.65, 130.92, 130.01, 129.33, 128.92, 128.47, 127.19, 123.78, 119.96, 116.83, 51.74, 45.89, 30.30, 23.64, 21.51. GC-MS: m/z found: 378 (M calculated for C22H22N2O2S: 378); m/z (%) = 379 (M + 1, 0.2), 378 (M, 1), 335 (14), 293 (24), 279 (6), 202 (11), 149 (2), 135 (5), 118 (8), 93 (12), 77 (10), 43 (100), 39 (10). -4-(2-p-tolylthiazol-4-yl) J = 23.7,16.5,11.5 Hz,2H),6.45 (t,J = 7.5 Hz,1H),3.10 (ddd,J = 24.6,16.5,7.5 Hz, 2H), 2.38 (s, 3H), 2.14 (s, 3H), 1.80 (s, 3H).…”

“…In this case, the formation of secondary products cannot be avoided, because of the lack of selectivity. Modern variants of the Mannich reaction have been proposed, either starting from pre-formed enolates [10], immonium salts [11], or by organometallic/organocatalytic methods [12]. Despite the notable successes achieved, the use of these chemical methods is generally limited by economical reasons, by the low stability of the intermediates and because of the toxicity of the solvents, intermediates and catalysts used.…”

Titanium Enolate Chemistry at the Beginning of the 21st Century

“…The last decade can be characterized by the growing interest in application of iminium salts as convenient electrophiles that allowed the Mannich reactions to be expanded beyond the classical range. Modern variants of the Mannich additions are represented by reactions of titanium(IV) enolates with stable iminium salts94 and in situ generated N ‐acyliminium ions92 and oxazolidine cations 93. Addition of prochiral titanium(IV) enolates to electrophilic N ‐acyliminium ion 60 led to target methylphenidate derivatives with high stereoselectivity and preferences for (2 R ,2′ R ) enantiomers over (2 R ,2′ S ) isomers.…”

“…The resulting Mannich adducts, important intermediates for a 1‐β‐methylcarbapenem synthesis, were formed with very high diastereoselectivity 96. Addition of D ‐camphor chlorotitanium(IV) enolates to reactive iminium salts, aminals, and N , O ‐acetals furnished adducts with very high exo diastereoselectivity 94…”