Pronounced Solvent and Concentration Effects in an Enantioselective Mukaiyama Aldol Condensation Using BINOL-Titanium(IV) Catalysts

Abstract

Recently we have reported reaction protocols for the catalytic asymmetric allylation (CAA reaction) of aldehydes using allylstannanes and chiral Lewis acid catalysts prepared from (R)-or (5>BINOL and Ti(0-i'-Pr)4.1 These procedures have proven remarkably efficient and especially convenient, since the chiral catalysts are prepared very simply in ca. 1 h from commercially available reagents. As the enantioselectivity exhibited in these reactions would appear to be derived solely from the structure of the chiral Lewis acid-aldehyde complex, it seemed obvious that other Lewis acid promoted reactions might be susceptible to enantioselective catalysis using the same procedures. We record herein the development of methodology using these catalysts for the catalytic enantioselective Mukaiyama aldol condensations2 of 1 -(ferf-butylthio)-1 -((trimethylsilyl)oxy)ethene with aldehydes to give /3-hydroxy thiol esters in high yields and with excellent enantiomeric excesses.3 In

Nonlinear Effects in Asymmetric Catalysis

“…Keck and Krishnamurthy [74] noticed a (+)-NLE in the catalyzed Mukaiyama aldol condensation of benzaldehyde with a ketene acetal [62; see Equation (17)]. The catalyst was prepared from binol and Ti(OiPr) 4 in the presence of molecular sieves.…”

The Transcriptional Coactivator p300 Plays a Critical Role in the Hypertrophic and Protective Pathways Induced by Phenylephrine in Cardiac Cells but Is Specific to the Hypertrophic Effect of Urocortin

“…We had difficulty reproducing the enantioselective reagent-controlled Carreira aldol conditions used by Simon et al [19] in their FK228 total synthesis. As an alternative, we explored Keck [20] conditions using BINOL as the catalyst, but both the chemical yield and enantioselectivity were poor. We then switched to a chiral auxiliary mediated aldol and used the Nagao thaiazolidinethione version [21] of the Evans auxiliary.…”

Titanium Binolate Catalyzed Aminolysis of meso Aziridines: A Highly Enantioselective and Direct Access to 1,2‐Diamines

“…In particular, the 6-phenyland 6-para-methoxyphenyl-6-azabicyclo[3.1.0]hexanes (1 c and 1 d, respectively) proved to be highly suitable substrates for this process and delivered, even using Ti(OiPr) 4 as the titanium source, trans-cyclopentane-1,2-diamines 3 g-l in excellent yields and enantioselectivities (up to > 99 % ee; Table 2, entries 8-12). Even the unsaturated meso-aziridine 1 e successfully underwent ring-opening with various anilines and furnished the corresponding 1,2-diamines 3 m-o in good yields and high enantioselectivities (Table 2, entries [13][14][15]. This process can also be applied to acyclic meso aziridines as was explicitly shown for N-phenyl-cis-2,3-dimethylaziridine (1 f) which upon reaction with aniline gave rise to (2S, 3S)-2,3-bisphenyl aminobutane (3 p) in 87 % yield and 90 % ee ( Table 2, entry 16).…”

“…[11] In particular, alkylations, [12] allylations, [13] aldol [14] and carbonyl-ene reactions [15] of aldehydes have been conducted in an asymmetric fashion using this catalyst system. It is remarkable, however, that the in situ preparation of the active chiral catalyst significantly differs from reaction to reaction with respect to titanium/binol stoichiometry, solvent, and the addition of water or molecular sieves.…”