Lewis acid promoted Mannich type reactions of α,α-dichloro aldimines with potassium organotrifluoroborates

Stas, Sara; Tehrani, Kourosch Abbaspour

doi:10.1016/j.tet.2007.06.003

Cited by 29 publications

(15 citation statements)

References 42 publications

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“…For more sterically hindered primary amines (e.g. tert ‐butyl and p ‐methoxybenzylamine) a more difficult procedure[8a] that makes use of TiCl 4 is needed (Method B). Imines 7 synthesized via these methods were generally pure enough to use as such in the next steps.…”

Section: Resultsmentioning

confidence: 99%

“…Polyhalogenated imines are a class of substrates that are interesting due to the increased electrophilicity of the C=N bond in comparison to non‐halogenated imines. Apart from additions of strong nucleophiles to the azomethine carbon (cyanation, Mannich‐type reactions), where the electrophilicity of the imine is of little importance, there are also examples of catalyzed nucleophilic additions to the azomethine carbon, in which enhanced electrophilicity is required . One‐pot nucleophilic addition to trichlorinated imines and sequential ring closing reactions often leads to interesting substrates, still bearing an electrophilic dichloromethylene group …”

Section: Introductionmentioning

confidence: 99%

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Synthesis of 3,3‐Dichloropiperidines and Further Functionalization via Pd‐Catalyzed Cross‐Coupling Reactions of the Dichloromethylene Moiety

et al. 2018

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A new synthetic methodology for the functionalization of the dichloromethylene moiety in 3,3‐dichloropiperidines via Pd‐catalyzed cross‐coupling reactions is reported. A range of 3,3‐dichloropiperidines was synthesized via a hydride induced cyclization of α,α,δ‐trichloroaldimines or an indium(III) triflate catalyzed alkynylation/cyclization procedure of α,α,δ‐trichloroaldimines. Subsequently, a dehydrochlorination followed by a cross‐coupling with the thus formed vinylic chloride was envisioned. The non‐alkynylated 3,3‐dichloropiperidines could be regioselectively eliminated and by careful choice of solvent and base both of the two regioisomeric vinyl chlorides could be exclusively formed. Palladium‐catalyzed Suzuki cross‐coupling of the thus formed 5‐chloro‐1,2,3,6‐tetrahydropyridines led to C3‐substituted 1,2,3,6‐tetrahydropyridines, which could be easily reduced to 3‐substituted piperidines, generating therapeutic agent (±)‐Preclamol for example. The 2‐alkynyl‐3,3‐dichloropiperidines were regioselectively eliminated giving the cyclic enamine, which was subsequently cross‐coupled in one‐pot. The presence of the alkynyl function, in this case, clearly directs elimination towards enamine structures. Hydrogenation of the resulting, unstable 2‐alkynyl‐3‐substituted‐1,2,3,4‐tetrahydropyridines, yields stable 2,3‐disubstituted piperidines.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis of 3,3‐Dichloropiperidines and Further Functionalization via Pd‐Catalyzed Cross‐Coupling Reactions of the Dichloromethylene Moiety

et al. 2018

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“…Since it has been proven [11] that fluorinated alcohols can have magnificent effects on the efficiency, regioselectivity, and stereoselectivity of several chemical transformations, further screening of the reaction conditions in CH 2 Cl 2 was performed using metal salts such as CuCl 2 , CuA C H T U N G T R E N N U N G (OTf) 2 , and AgOTf in the presence of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as an additive. We were gratified to observe that the yield of the desired product 3 a was increased to 37 % ( Table 1, entries 2-4) without the identifiable formation of any side products.…”

Section: Resultsmentioning

confidence: 99%

Lewis Acid Mediated Vinyl‐Transfer Reaction of Alkynes to N‐Alkylimines by Using the N‐Alkyl Residue as a Sacrificial Hydrogen Donor

Malakar

Stas

Herrebout

et al. 2013

Chemistry A European J

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A variety of N-alkyl-α,α-dichloroaldimines were vinylated by terminal acetylenes in the presence of Lewis acids such as In(OTf)3 or BF3 ⋅OEt2 and hexafluoroisopropanol (HFIP) as an additive. The reaction proceeds at ambient temperature and leads to geometrically pure allylic β,β-dichloroamines. This approach is complementary to previously reported transition-metal-catalyzed vinyl-transfer methods, which are not applicable to aliphatic imines and are restricted to imines that contain an electron-withdrawing nitrogen substituent. In the present approach, terminal alkynes were used as a source of the vinyl residue, and the N-alkyl moiety of the imine acts as a sacrificial hydrogen donor. The additional advantage of this methodology is the fact that no external toxic or hazardous reducing agents or molecular hydrogen has to be used. This new methodology nicely combines a C(sp(2) )C(sp) bond formation, hydride transfer, and an unusual cleavage of an unactivated CN bond, thereby giving rise to functionalized primary allylic amines. A detailed experimental study supported by DFT calculations of the mechanism has been done.

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“…Tetrabutylammonium bromide (VI) was dried in a desiccator over P 2 O 5 . Dibromofluoromethane [47], Schiff bases III [39,40], potassium trifluoroborates IX [48,49], and active lead [50] were prepared according to known procedures. Commercially available chemicals were used without preliminary purification, unless otherwise stated.…”

Section: Methodsmentioning

confidence: 99%

Monofluorinated aziridines in asymmetric synthesis of chiral fluorinated prop-2-yn-1-amines

et al. 2010

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Nonracemic C-fluoroaziridines were synthesized for the first time by reaction of fluorocarbene with N-diphenylmethylidene-substituted natural amino acid esters. The products were shown to be used in asymmetric synthesis of chiral fluorinated prop-2-yn-1-amines via one-pot process involving isomerization of 2-fluoroaziridines into α-fluoro imines and subsequent reaction with alkynyldifluoroborane generated in situ.Prop-2-yn-1-amines are widely used as medical agents for the treatment of various diseases [1-10] and as building blocks in the synthesis of polyfunctional nitrogen-containing organic compounds [11][12][13][14][15][16][17][18]. Development of convenient synthetic approaches to chiral prop-2-yn-1-amines [19][20][21][22][23][24][25] is an important problem, taking into account that the use of nonracemic drugs is one of the most important lines in modern medicine [26][27][28][29][30].We recently showed that fluorinated prop-2-yn-1-amines can readily be obtained by reaction of potassium arylethynyltrifluoroborates with 3-fluoro-2,2-diphenylaziridine in the presence of boron trifluorideether complex (Scheme 1) [31]. It was found that the formation of fluorinated prop-2-yn-1-amines from monofluoroaziridines involves Lewis acid-catalyzed isomerization of 2-fluoroaziridines into α-fluoro imines which then react with alkynyldifluoroborane. Acceleration of the process and reduction in the amount of by-products in the case of substrates containing a methoxycarbonylmethyl group (R = CH 2 CO 2 Me; A, R 1 = R 2 = H) was rationalized assuming formation of intermediate chelate A [31]. The formation of cyclic intermediate implies that addition of arylethynyl nucleophile at the C=N bond of substrates with a chiral carbon atom (C* in A, R 1 ≠ R 2 ) could occur with high diastereoselectivity due to rigidity of the transition state and proximity of the chiral center to the reaction center [32] (Scheme 1). Therefore, we presumed that the reaction sequence including isomerization of chiral aziridine and subsequent reaction of the imine thus formed with potassium alkynyltrifluoroborate should provide a simple and convenient synthetic route to chiral functionalized prop-2-yn-1-amines. The present article reports on our first results of asymmetric synthesis of fluorinated

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Lewis acid promoted Mannich type reactions of α,α-dichloro aldimines with potassium organotrifluoroborates

Cited by 29 publications

References 42 publications

Synthesis of 3,3‐Dichloropiperidines and Further Functionalization via Pd‐Catalyzed Cross‐Coupling Reactions of the Dichloromethylene Moiety

Synthesis of 3,3‐Dichloropiperidines and Further Functionalization via Pd‐Catalyzed Cross‐Coupling Reactions of the Dichloromethylene Moiety

Lewis Acid Mediated Vinyl‐Transfer Reaction of Alkynes to N‐Alkylimines by Using the N‐Alkyl Residue as a Sacrificial Hydrogen Donor

Monofluorinated aziridines in asymmetric synthesis of chiral fluorinated prop-2-yn-1-amines

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