874291-45-9

Upstream product

• 98-86-2 acetophenone 
• 343338-28-3 (S)-2-methylpropane-2-sulfinamide 

Downstream Products

• 1058227-17-0 ethyl diethoxymethyl-(S_S,R_C,R_P)-(+)-(1-(tert-butylsulfinylamino)-(1-phenylethyl))phosphinate 
• 1058227-35-2 ethyl diethoxymethyl-(S_S,R_C,S_P)-(+)-(1-(tert-butylsulfinylamino)-(1-phenylethyl))phosphinate 
• 1246465-10-0 (S)-N-((R)-1-(dibutylphosphoryl)-1-phenylethyl)-2-methylpropane-2-sulfinamide 
• 1246465-09-7 C₁₈H₃₂NO₂PS 
• 1246464-99-2 (S)-N-((R)-1-(diethylphosphoryl)-1-phenylethyl)-2-methylpropane-2-sulfinamide 
• 1316220-73-1 (2S,3S)-ethyl N-[tert-butyl-(S)-sulfinyl]-3-methyl-3-phenylaziridine-2-carboxylate 
• 1582803-13-1 (S)-N-((R)-4-fluoro-2-phenylpent-4-en-2-yl)-2-methylpropane-2-sulfinamide 
• 874291-44-8 2-methyl-N-(1-phenylethyl)propane-2-sulfinamide 
• 1360097-61-5 (S)-2-methyl-N-((R)-2-phenylpent-4-en-2-yl)propane-2-sulfinamide 

Relevant academic research and scientific papers

A Case Study in Catalyst Generality: Simultaneous, Highly-Enantioselective Br?nsted- And Lewis-Acid Mechanisms in Hydrogen-Bond-Donor Catalyzed Oxetane Openings

Generality in asymmetric catalysis can be manifested in dramatic and valuable ways, such as high enantioselectivity across a wide assortment of substrates in a given reaction (broad substrate scope) or as applicability of a given chiral framework across a variety of mechanistically distinct reactions (privileged catalysts). Reactions and catalysts that display such generality hold special utility, because they can be applied broadly and sometimes even predictably in new applications. Despite the great value of such systems, the factors that underlie generality are not well understood. Here, we report a detailed investigation of an asymmetric hydrogen-bond-donor catalyzed oxetane opening with TMSBr that is shown to possess unexpected mechanistic generality. Careful analysis of the role of adventitious protic impurities revealed the participation of competing pathways involving addition of either TMSBr or HBr in the enantiodetermining, ring-opening event. The optimal catalyst induces high enantioselectivity in both pathways, thereby achieving precise stereocontrol in fundamentally different mechanisms under the same conditions and with the same chiral framework. The basis for that generality is analyzed using a combination of experimental and computational methods, which indicate that proximally localized catalyst components cooperatively stabilize and precisely orient dipolar enantiodetermining transition states in both pathways. Generality across different mechanisms is rarely considered in catalyst discovery efforts, but we suggest that it may play a role in the identification of so-called privileged catalysts.

1,8-Diazabicyclo[5.4.0]undec-7-ene-mediated formation of N-sulfinyl imines

A facile and efficient method was developed for the preparation of a variety of aryl, heteroaryl, and alkyl N-sulfinyl imines using 1,8-diazabicyclo[5.4.0]undec-7-ene. In addition to tert-butanesulfinamide, the condensation is also effective with p-toluenesulfinamide. The reaction was performed at room temperature and produces the corresponding N-sulfinyl imines in excellent yields in the absence of acids, metals, and additives. This methodology is also useful for the preparation of N-sulfinyl imines on gram scale. A one-pot synthesis was developed using aryl and heteroaryl alcohols with both tert-butanesulfinamide and p-toluenesulfinamide at room temperature, resulting in the corresponding N-sulfinyl imines with good yields.

Stereoinvertive C–C Bond Formation at the Boron-Bound Stereogenic Centers through Copper-Bipyridine-Catalyzed Intramolecular Coupling of α-Aminobenzylboronic Esters

Enantiospecific intramolecular Suzuki–Miyaura-type coupling with α-(2-halobenzoylamino)benzylboronic esters to give 3-substituted isoindolinones is achieved by using copper catalysts with 2,2′-bipyridine-based achiral ligands. Enantioenriched α-aminobenzylboron reactants bearing a hydrogen atom at the boron-bound stereogenic carbons undergo stereoinvertive coupling in the presence of a 6-phenyl-2,2′-bipyridine ligand with high enantiospecificity. α-Aminobenzylboronates bearing fully substituted boron-bound stereogenic centers also gave the 3,3-disubstituted isoindolinones with stereospecific stereochemical inversion in the presence of simple 2,2′-bipyridine as a ligand.

Enantioselective Tail-to-Head Cyclizations Catalyzed by Dual-Hydrogen-Bond Donors

Chiral urea derivatives are shown to catalyze enantioselective tail-to-head cyclization reactions of neryl chloride analogues. Experimental data are consistent with a mechanism in which ?-participation by the nucleophilic olefin facilitates chloride ionization and thereby circumvents simple elimination pathways. Kinetic and computational studies support a cooperative mode of catalysis wherein two molecules of the urea catalyst engage the substrate and induce enantioselectivity through selective transition state stabilization.

Highly Enantioselective, Hydrogen-Bond-Donor Catalyzed Additions to Oxetanes

A precisely designed chiral squaramide derivative is shown to promote the highly enantioselective addition of trimethylsilyl bromide (TMSBr) to a broad variety of 3-substituted and 3,3-disubstituted oxetanes. The reaction provides direct and general access to synthetically valuable 1,3-bromohydrin building blocks from easily accessed achiral precursors. The products are readily elaborated both by nucleophilic substitution and through transition-metal-catalyzed cross-coupling reactions. The enantioselective catalytic oxetane ring opening was employed as part of a three-step, gram-scale synthesis of pretomanid, a recently approved medication for the treatment of multidrug-resistant tuberculosis. Heavy-atom kinetic isotope effect (KIE) studies are consistent with enantiodetermining delivery of bromide from the H-bond-donor (HBD) catalyst to the activated oxetane. While the nucleophilicity of the bromide ion is expected to be attenuated by association to the HBD, overall rate acceleration is achieved by enhancement of Lewis acidity of the TMSBr reagent through anion abstraction.

Transition-Metal-Free Hydrogen Autotransfer: Diastereoselective N-Alkylation of Amines with Racemic Alcohols

A practical method for the synthesis of α-chiral amines by alkylation of amines with alcohols in the absence of any transition-metal catalysts has been developed. Under the co-catalysis of a ketone and NaOH, racemic secondary alcohols reacted with Ellman's chiral tert-butanesulfinamide by a hydrogen autotransfer process to afford chiral amines with high diastereoselectivities (up to >99:1). Broad substrate scope and up to a 10 gram scale production of chiral amines were demonstrated. The method was applied to the synthesis of chiral deuterium-labelled amines with high deuterium incorporation and optical purity, including examples of chiral deuterated drugs. The configuration of amine products is found to be determined solely by the configuration of the chiral tert-butanesulfinamide regardless of that of alcohols, and this is corroborated by DFT calculations. Further mechanistic studies showed that the reaction is initiated by the ketone catalyst and involves a transition state similar to that proposed for the Meerwein–Ponndorf–Verley (MPV) reduction, and importantly, it is the interaction of the sodium cation of the base with both the nitrogen and oxygen atoms of the sulfinamide moiety that makes feasible, and determines the diastereoselectivity of, the reaction.

THERAPEUTIC COMPOUNDS AND METHODS OF USE THEREOF

The invention provides a compound of formula: or a salt thereof, wherein the variables RAA, n, ring A, ring B, R1a, R1b, R2, R3, R4, R5, R6, R7, R8, and R9 have the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions.

Improved Process for Preparation of tert-Butanesulfinyl Ketimines of Hindered Ketones under Nitrogen Flow

An improved process for tert-butanesulfinyl ketimines formation using titanium(IV) alkoxides is described. This new protocol gives better results especially for sterically hindered ketones compared to classical conditions where titanium(IV) isopropoxide i

Diastereoselective Hydrosilylation of N-(tert-Butylsulfinyl)imines Catalyzed by Zinc Acetate

An efficient zinc-catalyzed diastereoselective hydrosilylation of N-(tert-butylsulfinyl)imines has been developed that does not require the use of ligands or noble metals. A variety of N-(tert-butylsulfinyl)imines were reduced by this protocol in the presence of a catalytic amount of zinc acetate (5 mol-%) to provide the corresponding secondary amines in high yields with excellent diastereoselectivities (up to 98 % de). This experimentally simple catalytic procedure is easily applicable to the synthesis of both aromatic and aliphatic amines by using triethoxysilane as an efficient hydrogen source.

Triisopropyl borate mediated N-sulfinyl imine formation

Triisopropyl borate effects the condensation of aldehydes with sulfinamides to give N-sulfinyl imines. The reaction is amenable to 1°, 2°, and 3° alkyl aldehydes, as well as aryl, heteroaryl, and α,β-unsaturated aldehydes. In addition to tert-butanesulfin