A bifunctional iminophosphorane squaramide catalyzed enantioselective synthesis of hydroquinazolines<i>via</i>intramolecular aza-Michael reaction to α,β-unsaturated esters

Su, Guanglong; Thomson, Colin; Yamazaki, Ken; Rozsar, Daniel; Christensen, Kirsten E.; Hamlin, Trevor A.; Dixon, Darren J.

doi:10.1039/d1sc00856k

Cited by 23 publications

(10 citation statements)

References 97 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, Hamlin and Dixon have recently reported an IMAMR with conjugated esters as Michael acceptors. [40] The authors developed a novel bifunctional iminophosphoranesquaramide organocatalyst XIX to cyclize aniline-derived ureas 34 in toluene at room temperature. In this manner, hydroquinazoline derivatives 35 were obtained in excellent yields with good enantiocontrol (62-90 % ee) (Scheme 14).…”

Section: P E R S O N a L A C C O U N T T H E C H E M I C A L R E C O R Dmentioning

confidence: 99%

Two Decades of Progress in the Asymmetric Intramolecular aza‐Michael Reaction

Sánchez‐Roselló

Escolano

Gaviña

et al. 2021

The Chemical Record

View full text Add to dashboard Cite

The asymmetric intramolecular aza-Michael reaction (IMAMR) is a very convenient strategy for the generation of heterocycles bearing nitrogen-substituted stereocenters. Due to the ubiquitous presence of these skeletons in natural products, the IMAMR has found widespread applications in the total synthesis of alkaloids and biologically relevant compounds. The development of asymmetric versions of the IMAMR are quite recent, most of them reported in this century. The fundamental advances in this field involve the use of organocatalysts. Chiral imidazolidinones, diaryl prolinol derivatives, Cinchone-derived primary amines and quaternary ammonium salts, and BINOL-derived phosphoric acids account for the success of those methodologies. Moreover, the use of N-sulfinyl imines with a dual role, as nitrogen nucleophiles and as chiral auxiliaries, appeared as a versatile mode of performing the asymmetric IMAMR.

show abstract

Section: P E R S O N a L A C C O U N T T H E C H E M I C A L R E C O R Dmentioning

confidence: 99%

Two Decades of Progress in the Asymmetric Intramolecular aza‐Michael Reaction

Sánchez‐Roselló

Escolano

Gaviña

et al. 2021

The Chemical Record

View full text Add to dashboard Cite

show abstract

“…However, the enantioselective addition of (pro)nucleophiles to unactivated α,β-unsaturated amides under metal-free catalysis remains an unsolved problem. In 2013, our group disclosed a new class of superbasic catalysts, the bifunctional iminophosphorane (BIMP), which has proven to be exceptionally active in catalyzing challenging enantioselective conjugate additions. − Recognizing the limitations in enantioselective conjugate additions to α,β-unsaturated amides and seeking the opportunity to test the capabilities of new BIMP catalyst systems on conjugate acceptors at the bottom end of Mayr’s electrophilicity scale (Figure ), we sought to realize the first nonmetal-catalyzed enantioselective conjugate addition reaction to α,β-unsaturated amides. We chose to exemplify this with the sulfa-Michael addition (SMA).…”

Section: Introductionmentioning

confidence: 99%

Bifunctional Iminophosphorane-Catalyzed Enantioselective Sulfa-Michael Addition to Unactivated α,β-Unsaturated Amides

et al. 2022

Self Cite

View full text Add to dashboard Cite

The first metal-free catalytic intermolecular enantioselective Michael addition to unactivated α,β-unsaturated amides is described. Consistently high enantiomeric excesses and yields were obtained over a wide range of alkyl thiol pronucleophiles and electrophiles under mild reaction conditions, enabled by a novel squaramide-based bifunctional iminophosphorane catalyst. Low catalyst loadings (2.0 mol %) were achieved on a decagram scale, demonstrating the scalability of the reaction. Computational analysis revealed the origin of the high enantiofacial selectivity via analysis of relevant transition structures and provided substantial support for specific noncovalent activation of the carbonyl group of the α,β-unsaturated amide by the catalyst.

show abstract

“…[27] In fact, triethylamine (Et 3 N), 1,4-Diazabicyclo[2.2.2]octane (DABOC), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) were used as achiral organosuperbases in many reactions. In recent decade, several types of chiral organosuperbases [28,29] including amidine, [30][31][32] guanidine, [33][34][35][36][37][38][39][40][41] cyclopropenimine, [42][43][44][45][46][47] iminophosphorane, [48][49][50][51][52][53][54][55][56] and azaphosphatrane [57][58][59][60] have been developed and used as catalysts for direct deprotonation of substrates with high pK a values in asymmetric Michael reaction, Mannich reaction, amination, oxidation, aldol reaction and [3 + 2] cycloaddition. Benzophenone-protected glycine t-butyl ester 1 a bearing not only high pK a but also bulky group was regarded as a challenging substrate for asymmetric Michael addition.…”

Section: Introductionmentioning

confidence: 99%

Chiral Cyclopropenimine‐catalyzed Asymmetric Michael Addition of Bulky Glycine Imine to α,β‐Unsaturated Isoxazoles

Bai

Cheng

Zheng

et al. 2022

Chemistry An Asian Journal

View full text Add to dashboard Cite

A highly efficient asymmetric Michael addition of bulky glycine imine to α,β‐unsaturated isoxazoles has been achieved by using 5 mol% of chiral cyclopropenimine as a chiral organo‐superbase catalyst under mild conditions. Michael adducts were obtained in excellent yields (up to 97%) and stereoselectivities (up to >99 : 1 dr and 98% ee). A significant solvent effect was found in these chiral organosuperbase catalyzed asymmetric Michael reactions. Gram‐scale preparation of Michael adducts and their transformations are realized to provide corresponding products without loss of stereoselectivities. The configurations of Michael adduct was determined by single‐crystal X‐ray diffraction analysis.

show abstract

A bifunctional iminophosphorane squaramide catalyzed enantioselective synthesis of hydroquinazolinesviaintramolecular aza-Michael reaction to α,β-unsaturated esters

Abstract: An efficient synthesis of enantioenriched hydroquinazoline cores via a novel bifunctional iminophosphorane squaramide catalyzed intramolecular aza-Michael reaction of urea-linked α,β-unsaturated esters, is described. The methodology exhibits a high degree of...

Cited by 23 publications

References 97 publications

Two Decades of Progress in the Asymmetric Intramolecular aza‐Michael Reaction

Two Decades of Progress in the Asymmetric Intramolecular aza‐Michael Reaction

Bifunctional Iminophosphorane-Catalyzed Enantioselective Sulfa-Michael Addition to Unactivated α,β-Unsaturated Amides

Chiral Cyclopropenimine‐catalyzed Asymmetric Michael Addition of Bulky Glycine Imine to α,β‐Unsaturated Isoxazoles

Contact Info

Product

Resources

About