Synthesis of piperidines
A new efficient method for the N-heterocyclization of primary amines with diols catalyzed by a Cp*Ir complex was developed. A variety of five-, six-, and seven-membered cyclic amines were synthesized in good to excellent yields.
K.-I. Fujita, T. Fujii, R. Yamaguchi, Org. Lett., 2004, 6, 3525-3528.
A simple, one-pot preparation of cyclic amines via efficient chlorination of amino alcohols with use of SOCl2 obviates the need for the classical N-protection/O-activation/cyclization/deprotection sequence commonly employed for this type of transformation. The reaction pathways and the general scope of this method have also been investigated.
F. Xu, B. Simmons, R. A. Reamer, E. Corley, J. Murry, D. Tschaen, J. Org. Chem., 2008, 73, 312-315.
A one-pot synthesis of nitrogen-containing heterocycles from alkyl dihalides and primary amines and hydrazines occurs under microwave irradiation via a simple and efficient cyclocondensation in an alkaline aqueous medium.
Y. Ju, R. S. Varma, J. Org. Chem., 2006, 71, 135-141.
A ruthenium catalyzed, atom-economical domino redox isomerization/cyclization of easily available, linear aminopropargyl alcohols provides added-value nitrogen heterocycles in a single catalytic step and displays a broad scope and functional group tolerance.
B. M. Trost, N. Maulide, R. C. Livingston, J. Am. Chem. Soc., 2008, 130, 16502-16503.
The combination of chiral bicyclo[3.3.0]octadiene ligands, an active rhodium hydroxide complex, and neutral reaction conditions enabled a highly enantioselective rhodium-catalyzed arylation of aliphatic N-tosylaldimines in high yield. The application of this method is demonstrated by the enantioselective synthesis of chiral 2-aryl pyrrolidines and piperidines in a one-pot procedure.
Z. Cui, H.-J. Yu, F.-F. Yang, W.-Y. Gao, C.-G. Feng, G.-Q. Lin, J. Am. Chem. Soc., 2011, 133, 12394-12397.
Optically pure C2-symmetrical cyclic amines were efficiently synthesized from the corresponding diols obtained from an enantioselective borohydride reduction of diketones in the presence of a chiral β-ketoiminato cobalt(II) catalyst.
M. Sato, Y. Gunji, T. Ikeno, T. Yamada, Synthesis, 2004, 1434-1438.
Mild, rhodium-catalyzed hydroaminations of unactivated olefins with primary and secondary alkylamines form the corresponding five- and six-membered products in excellent yields. A variety of functional groups such as hydroxyl, halo, cyano, and carboalkoxyl groups were tolerated.
Z. Liu, J. F. Hartwig, J. Am. Chem. Soc., 2008, 130, 1570-1571.
HCl·DMPU induces the formation of (thiomethyl)methyl carbenium ion from DMSO under mild conditions. A subsequent reaction of this electrophile with homoallylic amines generates 4-chloropiperidines in good yields. The method applies to both aromatic and aliphatic amines. The reaction has a broad substrate scope and offers good chemical yields with high functional group tolerance and scalability.
R. Ebule, S. Mudshinge, M. H. Nantz, M. S. Mashuta, G. B. Hammond, B. Xu, J. Org. Chem., 2019, 84, 3249-3259.
The use of monodentate chiral spiro phosphoramidite ligands enables a highly enantioselective nickel-catalyzed intramolecular hydroalkenylation of easily accessible N- or O-tethered 1,6-dienes to provide very useful six-membered N- and O-heterocycles with high regioselectivity as well as excellent stereoselectivity under mild reaction conditions.
K. Li, M.-L. Li, Q. Zhang, S.-F. Zhu, Q.-L. Zhou, J. Am. Chem. Soc., 2018, 140, 7458-7461.
Use of a base-free Pd(DMSO)2(TFA)2 catalyst enables the synthesis of six-membered nitrogen heterocycles via a Wacker-type aerobic oxidative cyclization of alkenes. Various heterocycles, including morpholines, piperidines, piperazines and piperazinones, are accessible by this method.
Z. Lu, S. S. Stahl, Org. Lett., 2012, 14, 1234-1237.
A Pd-catalyzed reaction of vinyl iodides and N-tosylhydrazones assembles η3-allyl ligands through carbene insertion. Intramolecular trapping with nitrogen nucleophiles generates good yields of cinnamyl and pentadienyl amines like those found in alkaloid natural products.
A. Khanna, C. Maung, K. R. Johnson, T. T. Luong, D. L. Van Vranken, Org. Lett., 2012, 14, 3233-3235.
The combination of carbaboranylmercuric chloride as a bulky Lewis acid and silver triflate efficiently catalyzes a cycloisomerization of 1,3-dienes at room temperature to give allyl-substituted azacycles and cycloalkanes in excellent yields with very high regioselectivity.
H. Yamamoto, I. Sasaki, S. Shiomi, N. Yamasaki, H. Imagawa, Org. Lett., 2012, 14, 2250-2253.
The use of 5 mol % of AlCl3 as the catalyst and 2 equiv of a trimethylsilyl halide as the halide source enables aza-Prins cyclization of N-tosyl homoallylamine or Prins cyclization of homoallylic alcohol with carbonyl compounds to provide the corresponding trans-2-substituted-4-halopiperidines or cis-2-substituted-4-halotetrahydropyrans in high yields and satisfactory diastereoselectivity.
G.-Q. Liu, B. Cui, R. Xu, X.-M. Li, J. Org. Chem., 2016, 81, 5144-5161.
In the presence of 1.1 equiv of (Diacetoxyiodo)benzene (PIDA) and suitable halogen sources, a variety of olefins underwent haloamidation, haloetherification, and halolactonization to the corresponding 1,2-bifunctional cyclic skeletons in very good isolated yields. Subsequent mild nucleophilic substitution gives key intermediates for biologically interesting compounds in high yields.
G.-Q. Liu, Y.-M. Li, J. Org. Chem., 2014, 79, 10094-10109.
Iodocyclization of unsaturated tosylamides promoted by Oxone oxidation of KI afforded, in good yields, N-tosyl iodopyrrolidines and piperidines. A new, simple method for the conversion of alcohols to tosylamides is presented.
M. C. Marcotullio, V. Campagna, S. Sternativo, F. Costantino, M. Curini, Synthesis, 2006, 2760-2766.
A mild, effective gold(I)-catalyzed hydroamination of unactivated olefins to form protected nitrogen heterocycles has been developed. The substrate scope is broader than in reactions realized with late-transition-metal catalyst systems.
X. Han, R. A. Widenhoefer, Angew. Chem. Int. Ed., 2006, 45, 1747-1749.
Treatment of an N-4-pentenyl or N-5-hexenyl urea with a catalytic 1:1 mixture of a gold(I) N,N-diaryl imidazol-2-ylidine complex and AgOTf gave the corresponding nitrogen heterocycle in excellent yield via an intramolecular exo-hydroamination.
C. F. Bender, R. A. Widenhoefer, Org. Lett., 2006, 8, 5303-5305.
A mild and facile Pd-catalyzed intramolecular hydroamination of unactivated alkenes takes place at room temperature and tolerates acid-sensitive functional groups. The tridentate ligand on Pd effectively inhibits β-hydride elimination, thus the formation of hydroamination products is preferred over oxidative amination products.
F. E. Michael, B. M. Cochran, J. Am. Chem. Soc., 2006, 128, 4246-4247.
Hoveyda-Grubbs catalyst in combination with BF3·OEt2 efficiently promotes tandem cross metathesis intramolecular aza-Michael reaction between enones and unsaturated carbamates resulting in the creation of β-amino carbonyl units. The use of microwave irradiation dramatically accelerates the process, but also inverts the stereoselectivity in the addition process.
S. Fustero, D. Jiménez, M. Sánchez-Roselló, C. del Pozo, J. Am. Chem. Soc., 2007, 129, 6700-6701.
Key step of an eco-friendly and highly diastereoselective synthesis of substituted cis-2,6-piperidines and cis-2,6-tetrahydropyrans is an iron-catalyzed thermodynamic equilibration of 2-alkenyl 6-substituted piperidines and 2-alkenyl 6-substituted tetrahydropyrans allowing the isolation of enriched mixtures of the most stable cis-isomers.
A. Guérinot, A. Serra-Muns, C. Gnamm, C. Bensoussan, S. Reymond, J. Cossy, Org. Lett., 2010, 12, 1808-1811.
An asymmetric intramolecular hydroamination of allenes catalyzed by phosphinegold(I)-bis-p-nitrobenzoate complexes is applicable to the enantioselective formation of vinyl pyrrolidines and piperidines in high ee.
R. L. LaLonde, B. D. Sherry, E. J. Kang, F. D. Toste, J. Am. Chem. Soc., 2007, 129, 2452-2453.
The Au(I)-catalyzed intramolecular hydroamination of N-allenyl carbamates was effective for the formation of various cyclic amines. γ-Hydroxy and δ-hydroxy allenes underwent Au-catalyzed intramolecular hydroalkoxylation to form the corresponding oxygen heterocycles in good yield. 2-Allenyl indoles underwent Au-catalyzed intramolecular hydroarylation to form 4-vinyl tetrahydrocarbazoles in good yield.
Z. Zhang, C. Liu, R. E. Kinder, X. Han, H. Qian, R. A. Widenhoefer, J. Am. Chem. Soc., 2006, 128, 9066-9073.
tert-Butyl hypoiodite is a mild and powerful reagent for the cyclization of N-alkenylamides leading to various N-heterocycles. N-alkenylsulfonamides gave three- to six-membered saturated N-heterocycles in good yields, whereas alkenylbenzamide derivatives afforded N-, O- or N-, S-heterocycles.
S. Minakata, Y. Morino, Y. Oderaotoshi, M. Komatsu, Org. Lett., 2006, 8, 3335-3337.
An intramolecular anti-Markovnikov hydroamination of 1-(3-aminopropyl)vinylarenes occurred in the presence of [Rh(COD)(DPPB)]BF4 as catalyst to form 3-arylpiperidines in high yield. Reactants with substituents β to the amino group formed 3,5-disubstituted piperidines with high diastereomeric excess, whereas substituents in α and γ gave mostly enamines and isomerized starting materials.
A. Takemiya, J. F. Hartwig, J. Am. Chem. Soc., 2006, 128, 6042-6043.
A novel approach to 2,4-disubstituted piperidines involves the radical cyclization of 7-substituted-6-aza-8-bromooct-2-enoates. An enhancement in diastereoselectivity using tris(trimethylsilyl)silane instead of tributyltin hydride is discussed.
L. A. Gandon, A. G. Russel, T. Güveli, A. E. Brodwolf, B. M. Kariuki, N. Spencer, J. S. Snaith, J. Org. Chem., 2006, 71, 5198-5207.
A Pd-catalyzed, asymmetric 6-endo aminoacetoxylation of unactivated alkenes provides chiral β-acetoxylated piperidines with excellent chemo-, regio- and enantioselectivities under very mild reaction conditions using a designed pyridine-oxazoline (Pyox) ligand.
X. Qi, C. Chen, C. Hou, L. Fu, P. Chen, G. Liu, J. Am. Chem. Soc., 2018, 140, 7415-7419.
The combination of photoredox, cobaloxime, and amine catalysis mediates a radical cyclization of aldehydes with pendant alkenes to provide a variety of 5-, 6-, and 7-membered ring products with alkene transposition in good yields. The reaction exhibits wide functional group compatibility and occurs under mild conditions with extrusion of H2.
J. Li, J.-L. Tu, F. Liu, Org. Lett., 2020, 22, 7369-7372.
An intramolecular iodo-aldol cyclization of prochiral α-substituted enoate aldehydes and ketones produces hetero- and carbocycles containing quaternary centers adjacent to secondary or tertiary centers. The reactions occur in good yields and are highly trans-selective with hydroxyl and iodomethyl groups on opposite faces of the ring system.
F. Douelle, A. S. Capes, M. F. Greaney, Org. Lett., 2007, 9, 1931-1934.
An efficient method to activate hydroxyl groups of amino alcohols has been developed, which avoids the use of toxic reagents and tolerates various functional groups. This strategy has been applied to the synthesis of functionalized p-methoxyphenyl-protected azetidines, pyrrolidines, and piperidines.
R. M. de Figueiredo, R. Fröhlich, M. Christmann, J. Org. Chem., 2006, 71, 4147-4154.
A highly enantioselective rearrangement of β-amino alcohols was realized by using a catalytic amount of trifluoroacetic anhydride.
T.-X. Métro, D. G. Pardo, J. Cossy, J. Org. Chem., 2007, 72, 6556-6561.
Depending on the steric hindrance of the ligand, a regioselective palladium-catalyzed diamination of unactivated alkenes, provides either amino-functionalized piperidines or pyrrolidines. 6-Endo diamination occurred with a less sterically hindered quinox ligand to afford 3-aminopiperidines, while 5-exo diamination occurred with a bulky pyox ligand to give amino-substituted pyrrolidines.
X. Liu, C. Hou, Y. Peng, P. Chen, G. Liu, Org. Lett., 2020, 22, 9371-9375.
A borane catalyzed metal-free transfer hydrogenation of pyridines furnishes various piperidines in good yields with good cis-selectivities in the presence of ammonia borane as a hydrogen source. The ease in handling without requiring high pressure H2 makes this transfer hydrogenation practical and useful.
Q. Zhou, L. Zhang, W. Meng, X. Feng, J. Yang, H. Du, Org. Lett., 2016, 18, 5189-5191.
A mild, complete hydrogenation of aromatic rings catalyzed by heterogeneous 10% Rh/C proceeds at 80 °C in water under 5 atm of H2 pressure and is applicable to the hydrogenation of various carbon and heteroaromatic compounds such as alkylbenzenes, biphenyls, pyridines and furans.
Maegawa, A. Akashi, H. Sajiki, Synlett, 2006, 1440-1442.