Project description:We report the development of a catalytic method for the enantioselective addition of indoles to pyrone-derived electrophiles. Arylpyrrolidino-derived thioureas catalyze the addition with high stereoselectivity in the presence of catalytic quantities of an achiral Brønsted acid. The indole-pyrone adducts feature a quaternary stereocenter and represent an unusual class of indolines bearing structural resemblance to the hybrid natural product pleiocarpamine.
Project description:An enantioselective copper-catalyzed alkynylation of unstabilized cyclic iminium ions has been developed. Whereas such alkynylations typically utilize pyridinium, quinolinium and isoquinolinium intermediates, this method enables use of cyclic iminium ions unstabilized by resonance. With the use of a Lewis acid and copper catalyst, these iminium ions are generated in situ from readily available hemiaminal methyl ethers and transformed into highly enantioenriched α-alkynylated cyclic amines. A variety of terminal alkynes can be incorporated in high yields and enantiomeric excesses.
Project description:Asymmetric, catalytic reactions of oxocarbenium ions are reported. Simple, chiral urea and thiourea derivatives are shown to catalyze the enantioselective substitution of silyl ketene acetals onto 1-chloroisochromans. A mechanism involving anion binding by the chiral catalyst to generate a reactive oxocarbenium ion is invoked. Catalysts bearing tertiary benzylic amide groups afforded highest enantioselectivities, with the optimal structure being derived from enantioenriched 2-arylpyrrolidine derivatives.
Project description:γ- and δ-Oxoesters are easily available starting materials that have been sparingly used in some organocatalyzed reactions proceeding with a high enantioselectivity. In our experimentation we found that the use of these compounds as the enolizable (nucleophilic) component in organocatalyzed Mannich-type reactions using in situ-generated cyclic N-acyl iminium ions gave low diastereoselectivity and low to moderate values of enantioselectivity. This significant drop of facial selectivity with respect to simple aliphatic aldehydes has been rationalized by means of density functional theory (DFT) calculations.
Project description:An Ir-catalyzed asymmetric allylic alkylation of 3-substituted indoles is reported. The reaction provides indoline products containing multiple contiguous stereocenters with high site-, regio-, diastereo- and enantioselectivities in one step from a wide range of readily available starting materials. The key to this method is the high level of diastereocontrol enabled by an iridium catalyst derived from a N-aryl phosphoramidite ligand (Me-THQphos, 1c).
Project description:A new thiourea catalyst is reported for the enantioselective cationic polycyclization of hydroxylactams. Both the yield and enantioselectivity of this transformation were found to vary strongly with the identity of a single aromatic residue on a common catalyst framework, with more expansive and polarizable arenes proving optimal. Evidence is presented for a mechanism in which stabilizing cation-pi interactions are a principal determinant of enantioselectivity.
Project description:On the big screen: A chiral biphenol catalyst screening protocol was developed for the rapid identification of enantioselective nucleophilic boronate reactions with acyl imines (see scheme). The approach successfully identified a unique catalyst for the reaction of aryl, vinyl, and alkynyl boronates. Mechanistic studies demonstrate boronate ligand exchange with the catalyst is necessary for activation towards nucleophilic addition.
Project description:The new chiral amino thiourea catalyst 3d promotes the highly enantioselective cyanosilylation of a wide variety of ketones. The hindered tertiary amine substituent plays a crucial role with regard to both stereoinduction and reactivity, suggesting a cooperative mechanism involving electrophile activation by thiourea and nucleophile activation by the amine.
Project description:Masked acyl cyanide (MAC) reagents are shown to be effective umpolung synthons for enantioselective Michael addition to substituted enones. The reactions are catalyzed by chiral squaramides and afford adducts in high yields (90-99%) and with excellent enantioselectivities (85-98%). The addition products are unmasked to produce dicyanohydrins that, upon treatment with a variety of nucleophiles, provide γ-keto acids, esters, and amides. The use of this umpolung synthon has enabled, in enantiomerically enriched form, the first total synthesis of the prenylated phenol (+)-fornicin C.