146337-04-4

Upstream product

• 86953-79-9 tert-butyl pyrrolidine-1-carboxylate 
• 106-95-6 allyl bromide 
• 24424-99-5 di-tert-butyl dicarbonate 
• 1257660-73-3 1-azido-6-heptene 
• 19206-69-0 allyl diphenyl phosphate 

Downstream Products

• 155394-39-1 1-(o-bromobenzoyl)-2-(prop-2-enyl)pyrrolidine 
• 222624-10-4 tert-butyl hepta-4,6-dienylcarbamate 
• 222624-02-4 2-allyl-5-tributylstannanyl-pyrrolidine-1-carboxylic acid tert-butyl ester 
• 194154-91-1 (+/-)-1-(tert-Butoxycarbonyl)pyrrolidine-2-acetic acid 
• 1613330-73-6 (±)-2-allyl-N-(4-methoxyphenyl)pyrrolidine-1-sulfonamide 
• 1613331-05-7 (±)-2-allyl-N-(4-chlorophenyl)pyrrolidine-1-sulfonamide 
• 1613331-06-8 (±)-2-allyl-N-benzylpyrrolidine-1-sulfonamide 
• 1613331-07-9 (±)-2-allyl-N-(4-methoxybenzyl)pyrrolidine-1-sulfonamide 

Relevant academic research and scientific papers

Catalytic Synthesis of N-Heterocycles via Direct C(sp3)-H Amination Using an Air-Stable Iron(III) Species with a Redox-Active Ligand

Coordination of FeCl3 to the redox-active pyridine-aminophenol ligand NNOH2 in the presence of base and under aerobic conditions generates FeCl2(NNOISQ) (1), featuring high-spin FeIII and an NNOISQ radical ligand. The complex has an overall S = 2 spin state, as deduced from experimental and computational data. The ligand-centered radical couples antiferromagnetically with the Fe center. Readily available, well-defined, and air-stable 1 catalyzes the challenging intramolecular direct C(sp3)-H amination of unactivated organic azides to generate a range of saturated N-heterocycles with the highest turnover number (TON) (1 mol% of 1, 12 h, TON = 62; 0.1 mol% of 1, 7 days, TON = 620) reported to date. The catalyst is easily recycled without noticeable loss of catalytic activity. A detailed kinetic study for C(sp3)-H amination of 1-azido-4-phenylbutane (S1) revealed zero order in the azide substrate and first order in both the catalyst and Boc2O. A cationic iron complex, generated from the neutral precatalyst upon reaction with Boc2O, is proposed as the catalytically active species.

Synthesis of Cyclic Guanidines Bearing N-Arylsulfonyl and N-Cyano Protecting Groups via Pd-Catalyzed Alkene Carboamination Reactions

Palladium-catalyzed carboamination reactions of N-allylguanidines bearing cleavable N-cyano or N-arylsulfonyl protecting groups are described. The reactions afford cyclic guanidine products in good yield, and transformations of substrates bearing internal alkenes proceed with high diastereoselectivity. Deuterium labeling studies indicate these transformations proceed via anti-aminopalladation pathways.

Diamine-free lithiation-trapping of N-Boc heterocycles using s-BuLi in THF

A diamine-free protocol for the s-BuLi-mediated lithiation-trapping of N-Boc heterocycles has been developed. In the optimized procedure, lithiation is accomplished using s-BuLi in THF at -30 °C for only 5 or 10 min. Subsequent electrophilic trapping or transmetalation-Negishi coupling delivered a range of functionalized pyrrolidines, imidazolidines, and piperazines in 43-83% yield.

Regio- and enantioselective control in the reactions of α-(N-Carbamoyl)alkylcuprates with allylic phosphates

α-(N-Carbamoyl)alkylcuprates (RCuCNLi or R2CuLi) react with allylic phosphates to afford homoallylic amines in good chemical yields. Regioselectivity is governed by steric factors in both the cuprate reagent and phosphate substrate and systems can be designed to give either the S N2′ or SN2 substitution product cleanly. Excellent enantioselectivities can be achieved with either a scalemic α-di[(N- carbamoyl)-alkyl]cuprate and an achiral phosphate or with a scalemic allylic phosphate and an achiral cuprate reagent.

Reactivity and Enantioselectivity in the Reactions of Scalemic Stereogenic α-(N-Carbamoyl)alkylcuprates

Stereogenic 2-(N-carbamoyl)pyrrolidinylcuprates prepared from scalemic (i.e., enantioenriched) N-Boc-2-lithiopyrrolidine and THF soluble CuCN·2LiCl react with vinyl iodides, vinyl triflates, β-iodo-α,β-enoates, propargyl mesylates, and allyl bromide to afford the substitution products with excellent enantioselectivity. Excellent enantiomeric ratios are obtained in the conjugate addition reactions with methyl vinyl ketone while low enantiomeric ratios can be achieved with acrylate esters using HMPA/TMSCl activation. Enantiomeric ratios vary with substrate substitution patterns and the observed enantioselectivities appear to be more a function of cuprate-electrophile reactivities than of the reaction type (e.g., substitution, conjugate addition). Low enantiomeric ratios are obtained with the α-(N-carbamoyl)benzylcuprates. The lithium-copper transmetalation and cuprate vinylation reactions proceed with retention of configuration.

The steric course of S(E)2 reactions of unstabilized α- aminoorganolithiums: Distinguishing between SET and polar mechanisms

The competing mechanisms that determine the steric course of electrophilic aliphatic substitution reactions (S(E)2) of configurationally stable, unstabilized α-aminoorganolithiums are compared. The steric course of the reaction of lithiated pyrrolidines and piperidines with electrophiles is variable, such as when comparisons are made between two electrophiles and a single organolithium, or between two organolithiums and a single electrophile. The possible pathways considered are single electron transfer (SET) and competing polar substitutions (S(E)2ret vs S(E)2inv). Catalysis of organolithium racemization by the electrophile was eliminated as a possible source of racemic products. When the products are completely racemic, our evidence suggests that SET is the most likely mechanism; when polar pathways are operative, stereoselectivities vary from 75 to 100%, and may be invertive or retentive at the carbanionic carbon, depending on the electrophile.

Synthesis of 7-azabicyclo[2.2.1]heptanes by anionic cyclization

Cyclizations of α-amino-organolithiums, derived by tin-lithium exchange, which proceed via a stereoselective two-electron process and totally regiospecific 5-exo-trig ring closure, have been extended to the preparation of the 7-azabicyclo[2.2.1]heptane ring system. Cyclization occurs from either the cis or the trans isomer of 5-allyl-2-tri-n-butylstannyl-N- benzylpyrrolidine to give only the exo product as a single diastereomer in isolated yields up to 83%.

Synthesis of new trialkylsilylmethyloxazinones via intramolecular trapping of β-silyl carbocations by an N-Boc group

N-BoC amino ethers 1a-e when treated with allyltrialkylsilanes in the presence of TiCl4 afford the expected allylation compounds 2a-e and/or the unprecedented silylated oxazinones 3a-e or 4a-e.

α-Lithioamine Synthetic Equivalents: Synthesis of Diastereoisomers from Boc Derivatives of Cyclic Amines

Sequences of α'-lithiations and electrophilic substitutions of Boc-pyrrolidines, Boc-piperidines, and Boc-hexahydroazepines that provide compounds which are substituted adjacent to nitrigen are reported, and the pathways of the reactions are discussed.By this methodology monosubstituted 2 and disubstituted 2,4, 2,6, and 2,5 Boc-piperidines are obtained as single or separable diastereoisomers consistent with equatorial lithiations and retentive electrophilic substitution in chair conformations.Both cis and trans 2,6-disubstituted diastereoisomers can be prepared, and control of diastereoselectivity is demonstrated by syntheses of solenopsin A, a 2,6-trans-disubstituted piperidine, and of Boc-dihydropinidine, a 2,6-cis-disubstituted piperidine.In the case of 3-methoxy-Boc-piperidine elimination of methoxide occurs upon lithiation, and with cis-2,4-disubstituted Boc-piperidines the electrophile is introduced with trans stereochemistry at C-6.These reactions are suggested to involve twist boat conformations consistent with an X-ray crystal structure of 2-methyl-6-(trimethylstannyl)-4-phenyl-N-Boc-piperidine.Boc-pyrrolidine lithiates more rapidly than Boc-piperidine, provides 2-substituted products with electrophiles, and on further lithiation-substitution gives 2,5-cis- and -trans substituted products.Boc-perhydroazepine provides 2-substituted products by the sequence and on further lithiation-substitution gives 2,7-trans-disubstituted products.

Electroorganic chemistry 139. Electroreductive decyanation of nitriles and its application to synthesis of α-alkylamines

Electroreduction of nitriles gave the corresponding decyanated products when Zn was used as the material of cathode in aprotic solvent (DMF or MeCN) containing Et4NOTs as a supporting electrolyte. Alkylation of amines at the α-position was effectively achieved by cyanation of amines at the α-position, and α-alkylation of the resultant α-amino nitriles followed by the electroreductive decyanation.