Search for Chiral Catalysts Through Ligand Diversity: Substrate‐Specific Catalysts and Ligand Screening on Solid Phase

Abstract

An efficient strategy in the search for chiral catalysts is ligand optimization on solid support. This diversity approach provides unique opportunities for the identification of substrate‐specific catalysts and leads to the discovery of ligands with unusual properties that might have otherwise escaped detection. Thus, addition of TMSCN to cyclopentene oxide with ligands 1 or 2, which are very similar, results in opposite enantioselectivities (see reaction on the right; TMS = trimethylsilyl).

Facile Enantioselective Ring‐Opening Reaction of meso Epoxides with Anilines Using (S)‐(–)‐BINOL‐Ti Complex as a Catalyst

“…[1,2] A number of valuable products could be synthesized when reagents such as trialkylsilyl azide, [3][4][5][6] trimethylsilyl cyanide, [7][8][9][10] aryllithium, [11] halides [12][13][14] and alkylamines, [15] alcohols/phenols, [16,17] thiols, [18,19] as well as carboxylic acid [20] were used as nucleophiles for ring-opening reactions of epoxides. A catalytic asymmetric ring opening of meso-epoxide with aromatic amines is of particular interest because it has wider applications in the synthesis of pharmaceutically active compounds.…”

Catalytic Asymmetric Epoxide Ring‐opening Chemistry

“…Oguni discovered that the addition of trimethylsilyl cyanide to epoxides was catalyzed by titanium tetraisopropoxide and was accelerated in the presence of achiral tridentate Schiff-base ligands [43]. Building on this result, Snapper and Hoveyda used a combinatorial approach [44] and solidphase assembly [45] to identify an effective chiral catalyst for this transformation. After three generations of catalyst optimization, they identified a catalyst system based on ligand 13 and titanium for the desymmetrization of three representative meso-epoxides in the presence of TMSCN in moderate enantioselectivities and yields (Scheme 7.21).…”

“…The method was also applied to both s-cis and s-trans cyclic allylic epoxides (Schemes 7. 45 respectively), and in one case was applied in the generation of an all-carbon quaternary center in high enantiomeric excess. In addition, multigram, enantioselective syntheses of trans-4-methylcyclohex-2-en-1-ol and 4-methylcyclohex-2-en-1-one were developed [91].…”

Catalytic Enantioselective Ring-Opening Reaction of meso-Epoxides with ArSeH Using a (Salen)Ti(IV) Complex

“…Over past several decades, various nucleophiles such as RNH 2 [2,3], ROH [4], TMSCN [5], RN 3 [6], and RSH [7,8] have been widely investigated in the reaction catalyzed by various chiral catalysts to obtain 1,2-amino alcohols, 1,2-diol monoethers, 1,2-cyano alcohols, 1,2-azidoalcohols, as well as 1,2-mercaptoalcohols, respectively [9,10]. Chiral organoselenium compounds have been employed as useful ligands, catalysts, or intermediates in various asymmetric transformations such as diethylzinc addition to aldehydes, asymmetric hydrosilylation, and 1,4-addition of Grignard reagents to enones [11][12][13].…”