Quaternary β^2,2-amino acid derivatives by asymmetric addition of isoxazolidin-5-ones to para-quinone methides

Abstract

Novel densely functionalized β2,2-amino acids were obtained in almost enantiopure form using down to 20 ppm of a chiral phase-transfer catalyst.

Isothiourea-Catalyzed Enantioselective α-Alkylation of Esters via 1,6-Conjugate Addition to para-Quinone Methides

“…While ortho-QMs have been used extensively in enantioselective catalysis [19], particularly as components in formal [4+2] cycloaddition reactions, the use of para-QMs has only recently received increased attention [19][20][21][22][23]. The majority of enantioselective organocatalytic methods that involve para-QMs have utilized Brønsted acid [24][25][26][27][28][29][30][31][32][33] or hydrogen bonding catalysts [34][35][36][37][38], with only a relatively small number of examples using Lewis base catalysis [39][40][41][42][43][44][45][46][47][48][49][50][51].…”

Enantioselective Synthesis of Acyclic Orthogonally Functionalized Compounds Bearing a Quaternary Stereocenter Using Chiral Ammonium Salt Catalysis

“…Our groups have been engaged in the design and use of chiral ammonium salt catalysts for (novel) asymmetric α-(hetero)functionalizations of prochiral C-nucleophiles for a while. [10,11] Based on the general high interest in acyclic compounds bearing a quaternary stereogenic center we now became interested in introducing the novel orthogonally functionalized α-cyanoacetates 3 as a versatile substrate for (chiral ammonium salt-catalyzed) asymmetric α-alkylations. [12] As outlined in Scheme 1, these starting materials should be accessible by alkylation of cyanoacetates 1 with the dioxolane-based electrophile 2 and asymmetric αalkylations with Csp 3 -based electrophiles 4 will give access to the highly functionalized chiral acyclic targets 5 then.…”

CF3‐Containing para‐Quinone Methides for Organic Synthesis

“…Interestingly, in 1985 already Umemoto and co-workers described the formation of a CF 3 -containing p-QM [11] and the intermediate formation of CF 3 -containing p-QMs was also observed in reactions of trifluoroethanol-containing phenols some years ago, [12] but apart from these two reports, such potentially useful building blocks have not been reported and utilized for further transformations until very recently, when we described the first synthesis of the CF 3 -QM 1a. [13,14] Starting from the bulk chemical 2, p-QM 1a could be obtained in two steps via a benzylic trifluoromethylation first, [15] followed by oxidation to the QM (Scheme 1C). [13,16] This compound was then successfully used in the asymmetric phase-transfer catalyst (PTC) controlled reaction with pronucleophile 3 to access the masked β 2,2 -amino acid derivative 4 with very high levels of stereoselectivity.…”

“…[13,14] Starting from the bulk chemical 2, p-QM 1a could be obtained in two steps via a benzylic trifluoromethylation first, [15] followed by oxidation to the QM (Scheme 1C). [13,16] This compound was then successfully used in the asymmetric phase-transfer catalyst (PTC) controlled reaction with pronucleophile 3 to access the masked β 2,2 -amino acid derivative 4 with very high levels of stereoselectivity. [13] Considering this very promising initial application of the novel building block 1a, we now became interested in investigating this novel quinone methide-platform more systematically (Scheme 1B).…”

“…[13,16] This compound was then successfully used in the asymmetric phase-transfer catalyst (PTC) controlled reaction with pronucleophile 3 to access the masked β 2,2 -amino acid derivative 4 with very high levels of stereoselectivity. [13] Considering this very promising initial application of the novel building block 1a, we now became interested in investigating this novel quinone methide-platform more systematically (Scheme 1B). Besides utilizing 1a for a variety of different transformations, we also wanted to install alternative groups R at the phenol part, and we became interested in determining the electrophilicity parameter E for at least one (stable) derivative.…”