ABSTRACT
An efficient asymmetric synthesis of 11-ß-HSD inhibitor 1 has been accomplished in five linear steps and 53% overall yield, starting from the readily available 3-chloro-1-phenylpropan-1-one. The key feature of the synthesis includes an asymmetric methallylation of 3-chloro-1-phenylpropan-1-one catalyzed by the highly effective organocatalyst (S)-3,3'-F2-BINOL under solvent-free and metal-free conditions.
Subject(s)
11-beta-Hydroxysteroid Dehydrogenases/antagonists & inhibitors , Naphthols/chemical synthesis , Propane/analogs & derivatives , 11-beta-Hydroxysteroid Dehydrogenases/chemistry , Catalysis , Ketones/chemistry , Naphthols/chemistry , Propane/chemical synthesis , Propane/chemistry , StereoisomerismABSTRACT
A general, scalable, and highly diastereoselective aziridination of N-tert-butanesulfinyl ketimino esters is described. The methodology has been utilized to provide straightforward access to previously unobtainable, biologically relevant α-quaternary amino esters and derivatives starting from readily available precursors.
Subject(s)
Aza Compounds/chemistry , Aziridines/chemical synthesis , Aziridines/chemistry , Catalysis , Esters , Molecular Structure , StereoisomerismABSTRACT
A practical and efficient synthesis of a complex chiral atropisomeric HIV integrase inhibitor has been accomplished. The combination of a copper-catalyzed acylation along with the implementation of the BI-DIME ligands for a ligand-controlled Suzuki cross-coupling and an unprecedented bis(trifluoromethane)sulfonamide-catalyzed tert-butylation renders the synthesis of this complex molecule robust, safe, and economical. Furthermore, the overall synthesis was conducted in an asymmetric and diastereoselective fashion with respect to the imbedded atropisomer.
Subject(s)
HIV Integrase Inhibitors/chemical synthesis , HIV Integrase/chemistry , HIV/enzymology , Acylation , Catalysis , Copper/chemistry , HIV Integrase/metabolism , HIV Integrase Inhibitors/chemistry , Humans , Ligands , Stereoisomerism , Sulfonamides/chemistryABSTRACT
A highly concise and convergent synthesis of HCV polymerase inhibitor Deleobuvir (BI 207127, 1) was achieved, featuring efficient Pd-catalyzed one-pot borylation-Suzuki coupling where TFP was identified as the unique ligand effective for these transformations.
Subject(s)
Acrylates/chemical synthesis , Acrylates/pharmacology , Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacology , Benzimidazoles/chemical synthesis , Benzimidazoles/pharmacology , Acrylates/chemistry , Antiviral Agents/chemistry , Benzimidazoles/chemistry , Catalysis , Hepacivirus/drug effects , Hepacivirus/enzymology , Ligands , Molecular Structure , Palladium/chemistryABSTRACT
A solvent- and metal-free process has been developed for the direct methallylboration of ketones employing the stable B-methallylborinane 1, which was accelerated by tertiary alcohols. In the presence of 2.0 equiv of readily available tertiary alcohols such as tert-amyl alcohol, the methallylation products were prepared at room temperature in excellent yields. The salient features of the described process include simple operation, high efficiency, and mild reaction conditions.
Subject(s)
Alcohols/chemistry , Alcohols/chemical synthesis , Boranes/chemistry , Ketones/chemistry , Molecular StructureABSTRACT
A practical one-pot and regiospecific three-component process for the synthesis of 2,3-disubstituted indoles from 2-bromoanilides was developed via consecutive palladium-catalyzed Sonogashira coupling, amidopalladation, and reductive elimination.
Subject(s)
Amides/chemistry , Anilides/chemistry , Hydrocarbons, Brominated/chemistry , Indoles/chemical synthesis , Palladium/chemistry , Catalysis , Cyclization , Indoles/chemistry , Molecular Structure , Organometallic Compounds/chemistry , Oxidation-ReductionABSTRACT
Carbamoyl anions, generated from N,N-disubstituted formamides and lithium diisopropylamide, add with high diastereoselectivity to chiral N-sulfinyl aldimines and ketimines to provide α-amino amides. The methodology enables the direct introduction of a carbonyl group without the requirement of unmasking steps as with other nucleophiles. The products may be converted to α-amino esters or 1,2-diamines. Iterative application of the reaction enabled the stereoselective synthesis of a dipeptide. Spectroscopic and computational studies support an anion structure with η(2) coordination of lithium by the carbonyl group.
Subject(s)
Amides/chemistry , Amides/chemical synthesis , Imines/chemistry , Chemistry Techniques, Synthetic , Dipeptides/chemical synthesis , Dipeptides/chemistry , Models, Molecular , Molecular Conformation , Stereoisomerism , Substrate SpecificityABSTRACT
(S)-3,3'-F2-BINOL has been synthesized for the first time and demonstrated as a highly active organocatalyst for asymmetric methallylation of ketones. Up to 98:2 enantioselectivity and 99% yield were obtained with 5 mol % catalyst loading. The catalyst (S)-3,3'-F2-BINOL could be easily recovered and reused.
Subject(s)
Ketones/chemistry , Naphthols/chemistry , Catalysis , Molecular Structure , StereoisomerismABSTRACT
A general, efficient, and highly diastereoselective method for the synthesis of structurally and sterically diverse P-chiral phosphine oxides was developed. The method relies on sequential nucleophilic substitution on the versatile chiral phosphinyl transfer agent 1,3,2-benzoxazaphosphinine-2-oxide, which features enhanced and differentiated P-N and P-O bond reactivity toward nucleophiles. The reactivities of both bonds are fine-tuned to allow cleavage to occur even with sterically hindered nucleophiles under mild conditions.
Subject(s)
Cyclic P-Oxides/chemical synthesis , Phosphines/chemical synthesis , Cyclic P-Oxides/chemistry , Ligands , Molecular Structure , Phosphines/chemistry , StereoisomerismABSTRACT
A series of novel P-chiral monophosphorus ligands exhibit efficiency in asymmetric Suzuki-Miyaura coupling reactions, enabling the construction of an array of chiral biaryl products in high yields and excellent enantioselectivities (up to 96% ee) under mild conditions. The carbonyl-benzooxazolidinone moiety in these chiral biaryl products allows facile derivatization for further synthetic applications. A computational study has revealed that a π-π interaction between the two coupling partners can enhance the enantioselectivity of the coupling reaction.
Subject(s)
Benzoxazoles/chemistry , Organophosphorus Compounds/chemistry , Palladium/chemistry , Catalysis , Combinatorial Chemistry Techniques , Ligands , Molecular Structure , Organophosphorus Compounds/chemical synthesis , StereoisomerismABSTRACT
A process has been designed and demonstrated for the asymmetric synthesis of sulfinamides using quinine as auxiliary. A variety of chiral sulfinamides including N-alkyl sulfinamides with diverse structure were prepared in good yields and excellent enantioselectivity starting from easily available and inexpensive reagents. The auxiliary quinine could be recovered and recycled.
Subject(s)
Quinine/chemistry , Sulfonamides/chemical synthesis , Sulfonium Compounds/chemical synthesis , Indicators and Reagents/chemistry , Molecular Structure , Stereoisomerism , Sulfonamides/chemistry , Sulfonium Compounds/chemistryABSTRACT
An operationally simple copper-BINAP-catalyzed, highly enantioselective propargylation of ketones is presented. The methodology was developed as an enantioselective process for methyl ethyl ketone and shown to be applicable to a wide variety of prochiral ketones. The resulting homopropargyl adducts are versatile latent carbonyls from which γ-butyrolactones, ß-hydroxy methyl ketones, and ß-hydroxycarboxylates are readily obtained.
Subject(s)
Boronic Acids/chemistry , Butanones/chemistry , Copper/chemistry , Ketones/chemistry , Naphthalenes/chemistry , Catalysis , Pargyline/chemistryABSTRACT
A one-pot process has been developed for the synthesis of 8-arylquinolines via Pd-catalyzed borylation of quinoline-8-yl halides and subsequent Suzuki-Miyaura coupling with aryl halides using n-BuPAd(2) as ligand. Yields of up to 98% were obtained.
Subject(s)
Hydrocarbons, Halogenated/chemistry , Palladium/chemistry , Quinolines/chemical synthesis , Catalysis , Ligands , Molecular Structure , Quinolines/chemistryABSTRACT
A new chiral sulfinyl transfer auxiliary derived from readily available phenylglycine was developed. This auxiliary is utilized to synthesize a diverse array of alkyl- and arylsulfinamides and sulfinylferrocenes in high yields and excellent ee's. The desired products are produced in a one-pot sequence from the oxathiazolidine 2-oxide by two sequential nucleophilic additions that proceed in a stereospecific manner.
Subject(s)
Amides/chemical synthesis , Ferrous Compounds/chemical synthesis , Glycine/chemistry , Sulfhydryl Compounds/chemical synthesis , Amides/chemistry , Ferrous Compounds/chemistry , Glycine/analogs & derivatives , Metallocenes , Molecular Structure , Stereoisomerism , Sulfhydryl Compounds/chemistryABSTRACT
A general and efficient zinc-alkoxide-catalyzed allylation of a diverse array of ketones with allyl boronates is presented. The methodology is effective with 2 mol % of catalyst and with relatively short reaction times. Studies of the key exchange process are presented, which support a cyclic transition state for the boron to zinc exchange.
Subject(s)
Allyl Compounds/chemistry , Boron Compounds/chemistry , Ketones/chemistry , Zinc/chemistry , Catalysis , Combinatorial Chemistry Techniques , Molecular StructureABSTRACT
A superior, mild, high-yielding one-pot process for rapid access to oxo anilides has been developed that involves three cascade reactions: iodine-magnesium exchange, regiospecific ortho N-Fries rearrangement, and in situ trapping of the formed aniline anion. Coupled with McMurry cyclization, the two-step process allows ready synthesis of strained 1,2,3-trisubstituted indoles regioselectively.
Subject(s)
Anilides/chemistry , Indoles/chemical synthesis , Iodine/chemistry , Magnesium/chemistry , Anions , Indoles/chemistryABSTRACT
[Structure: see text] A practical one-pot, regiospecific three-component process for the synthesis of 2,3-disubstituted indoles was developed via consecutive Pd-catalyzed Sonogashira coupling, amidopalladation, and reductive elimination.