Asymmetric synthesis of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates

Sharland, Jack C.; Wei, Bo; Hardee, David J.; Hodges, Timothy R.; Gong, Wei; Voight, Eric A.; Davies, Huw M. L.

doi:10.1039/d1sc02474d

Cited by 33 publications

(45 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, while complete reaction of diazo coupling partner 10-(S) occurred within 1 h at room temperature, 10-(R) required 5 h to react completely, presumably because of more effective coordination of its basic oxazoline nitrogen to the chiral catalyst to compete with coordination and reaction of the diazo carbon. 28 Straightforward sulfur oxidation and ester decarboxylation of sulfilimines 11 and 12 were next carried out. Attempts to cleave the N-acyl group under basic hydrolytic conditions led to competitive epimerization of the oxazoline stereocenter as well as methoxide S N Ar displacement of one of the fluorine substituents.…”

mentioning

confidence: 99%

Catalytic Enantioselective Sulfur Alkylation of Sulfenamides for the Asymmetric Synthesis of Sulfoximines

2022

View full text Add to dashboard Cite

Sulfoximines are increasingly incorporated in agrochemicals and pharmaceuticals, with the two enantiomers of chiral sulfoximines often having profoundly different binding interactions with biomolecules. Therefore, their application to drug discovery and development requires the challenging preparation of single enantiomers rather than racemic mixtures. Here, we report a general and fundamentally new asymmetric synthesis of sulfoximines. The first S-alkylation of sulfenamides, which are readily accessible sulfur compounds with one carbon and one nitrogen substituent, represents the key step. A broad scope for S-alkylation was achieved by rhodium-catalyzed coupling with diazo compounds under mild conditions. When a chiral rhodium catalyst was utilized with loadings as low as 0.1 mol %, the S-alkylation products were obtained in high yields and with enantiomeric ratios up to 98:2 at the newly generated chiral sulfur center. The S-alkylation products were efficiently converted to a variety of sulfoximines with complete retention of stereochemistry. The utility of this approach was further demonstrated by the asymmetric synthesis of a complex sulfoximine agrochemical.

show abstract

mentioning

confidence: 99%

Catalytic Enantioselective Sulfur Alkylation of Sulfenamides for the Asymmetric Synthesis of Sulfoximines

2022

View full text Add to dashboard Cite

show abstract

“…Likewise, heterocyclic analogues such as 2-vinylthiophene are suitable substrates, as are different enamine and enamide derivatives, which afford particularly high trans/cis ratios at the limits of detection (≥50:1). The scope also nicely extends to aliphatic alkenes, including functionalized compounds such as allyltrimethylsilane and allyl acetate, which lead to multifunctionalized compounds for further use as valuable building blocks in the life sciences. , The fact that terminal olefins react much faster than disubstituted π-bonds is likely rooted in the congested binding site about the active rhodium center of C10 . This selectivity is enabling in reactions with polyunsaturated substrates: compounds 2r–v derived from a 1,3-enyne, a silyloxydiene, myrcene, or ordinary 1,3-dienes respectively, illustrate this point.…”

Section: Resultsmentioning

confidence: 99%

From Serendipity to Rational Design: Heteroleptic Dirhodium Amidate Complexes for Diastereodivergent Asymmetric Cyclopropanation

et al. 2022

View full text Add to dashboard Cite

A heteroleptic dirhodium paddlewheel complex comprising three chiral carboxylate ligands and one achiral acetamidate ligand has recently been found to be uniquely effective in catalyzing the asymmetric cyclopropanation of olefins with α-stannylated (silylated and germylated) α-diazoacetate derivatives. A number of control experiments in combination with detailed computational studies provide compelling evidence that an interligand hydrogen bond between the −NH group of the amidate and the ester carbonyl group of the reactive rhodium carbene intermediate plays a quintessential role in the stereodetermining transition state. The penalty for distorting this array outweighs steric arguments and renders two of the four conceivable transitions states unviable. Based on this mechanistic insight, the design of the parent catalyst is revisited herein: placement of appropriate peripheral substituents allows high levels of diastereocontrol to be imposed upon cyclopropanation, which the original catalyst lacks. Because the new complexes allow either trans- or cis-configured stannylated cyclopropanes to be made selectively and in excellent optical purity, this transformation also marks a rare case of diastereodivergent asymmetric catalysis. The products are amenable to stereospecific cross coupling with aryl halides or alkenyl triflates; these transformations appear to be the first examples of the formation of stereogenic quaternary carbon centers by the Stille reaction; carbonylative coupling is also achieved. Moreover, tin/lithium exchange affords chiral lithium enolates, which can be intercepted with a variety of electrophilic partners. The virtues and inherent flexibility of this new methodology are illustrated by an efficient synthesis of two salinilactones, extremely scarce bacterial metabolites with signaling function involved in the self-regulatory growth inhibition of the producing strain.

show abstract

“…Since the seminal work of Grignard reagents addition to 2-alkenylquinolines reported by Hoffman, Farlow, and Fuson, alkenyl-substituted N -heteroarenes have been recognized as potential Michael acceptors . However, few studies on its use in the catalytic asymmetric cycloaddition have been described, presumably due to the low activation from the N -heteroaryl group and the potential deactivation of the catalysts caused by coordination of the Lewis basic nitrogen of the heteroarene to the metal cation. Wang and co-workers developed a chiral amine and a Brønsted acid cocatalyzed enantioselective [4 + 2] cycloaddition of vinylquinolines with dienals, but this transformation suffered from the formation of a mixture of diastereoisomers (Scheme a) .…”

mentioning

confidence: 99%

Enantioselective [3 + 2] Cycloaddition of Vinylcyclopropanes with Alkenyl N-Heteroarenes Enabled by Palladium Catalysis

et al. 2022

View full text Add to dashboard Cite

show abstract

Asymmetric synthesis of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates

Abstract: The dirhodium tetracarboxylate-catalysed asymmetric cyclopropanation has been applied to the enantioselective syntheses of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates.

Cited by 33 publications

References 64 publications

Catalytic Enantioselective Sulfur Alkylation of Sulfenamides for the Asymmetric Synthesis of Sulfoximines

Catalytic Enantioselective Sulfur Alkylation of Sulfenamides for the Asymmetric Synthesis of Sulfoximines

From Serendipity to Rational Design: Heteroleptic Dirhodium Amidate Complexes for Diastereodivergent Asymmetric Cyclopropanation

Enantioselective [3 + 2] Cycloaddition of Vinylcyclopropanes with Alkenyl N-Heteroarenes Enabled by Palladium Catalysis

Contact Info

Product

Resources

About