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Synthesis of allylic amines


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Tsuji-Trost Reaction

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The use of aqueous ammonia is essential for a palladium-catalyzed allylic amination for the preparation of primary amines. It is noteworthy that ammonia gas did not react at all. The first catalytic asymmetric synthesis using aqueous ammonia as a nitrogen source has also been demonstrated.
T. Nagano, S. Kobayashi, J. Am. Chem. Soc., 2008, 131, 4200-4201.

Phosphinoamide-scaffolded heterobimetallic palladium-titanium complexes are highly effective catalysts for allylic aminations of allylic chlorides with hindered secondary amine nucleophiles. Various sterically bulky secondary amines are efficiently allylated in high yields with low catalyst loadings. Piperidine and pyrrolidine products are also efficiently generated via intramolecular aminations.
W. K. Walker, D. L. Anderson, R. W. Stokes, S. J. Smith, D. J. Michaelis, Org. Lett., 2015, 17, 752-755.

A simple Re2O7-catalyzed direct dehydrative coupling between π-activated alcohols with electron-deficient amines has been achieved under mild and open flask conditions. The protocol alows the conversion of allylic, benzylic, and propargylic alcohols. The mechanistic proof for the SN1-type process has also been provided.
B. G. Das, R. Nallagonda, P. Ghorai, J. Org. Chem., 2012, 77, 5577-5583.

Iridium catalysts derived from a phosphoramidite containing a biphenolate group, one distal chiral substituent at nitrogen and a large achiral cycloalkyl group were shown to react in all cases examined with nearly the same rates, regioselectivities, and enantioselectivities as catalysts derived from the previously reported, more elaborate ligands.
A. Leitner, S. Shekhar, M. J. Pouy, J. F. Hartwig, J. Am. Chem. Soc., 2005, 127, 15506-15514.

Palladium-catalyzed isomerization of readily accessible racemic, branched aromatic allylic esters to terminal allylic esters, followed by sequential iridium-catalyzed allylic substitution, gave branched allylic amines, ethers, and alkyls in good yield with high regioisomeric and enantiomeric selectivity.
S. Shekhar, B. Trantow, A. Leitner, J. F. Hartwig, J. Am. Chem. Soc., 2006, 128, 11770-11771.

The allylic amination and etherification of a broad range of allylic carbonates occurred in high yields and with high regioselectivities and enantioselectivities with an activated metallacyclic iridium catalyst containing a bis-naphthethylamino group.
A. Leitner, C. Shu, J. F. Hartwig, Org. Lett., 2005, 7, 1093-1096.

An iridium-catalyzed enantioselective allylic amination of (E)-cinnamyl and terminal aliphatic allylic carbonates using chiral phosphoramidites as ligands provided branched secondary and tertiary allylic amines in high yields with excellent regio- and enantioselectivity. Reactions in THF displayed the most suitable balance of rate and enantioselectivity.
T. Ohmura, J. F. Hartwig, J. Am. Chem. Soc., 2002, 124, 15164-15165.

An efficient aerobic linear allylic C-H amination under palladium(II)/bis-sulfoxide/Brønsted base catalysis operates under operationally simple conditions (1 equiv of olefin, 1 atm O2 or air) with reduced catalyst loadings while providing higher turnovers and product yields than systems employing stoichiometric benzoquinone (BQ) as the terminal oxidant.
C. P. Pattillo, I. I. Strambeanu, P. Calleja, N. A. Vermeulen, T. Mizuno, M. C. White, J. Am. Chem. Soc., 2016, 138, 1265-1272.

A direct catalytic amination of allylic alcohols without the use of activating reagents is promoted by the combination of platinum and the large bite-angle ligand DPEphos. The use of the DPEphos ligand was essential for obtaining high catalyst activity and high monoallylation selectivity of primary amines, allowing the formation of various monoallylated products in good yield.
M. Utsunomiya, Y. Miyamoto, J. Ipposhi, T. Ohshima, K. Mashima, Org. Lett., 2007, 9, 3371-3374.

A ligand-free copper-catalyzed hydroamination of allenes with cyclic secondary amines or anilines derivatives provides (E)-allylamines under smooth conditions with total regio- and stereoselectivity.
R. Blieck, J. Bahri, M. Taillefer, F. Monnier, Org. Lett., 2016, 18, 1482-1485.

A rhodium-catalyzed regioselective amination of tertiary allylic trichloroacetimidates with unactivated aromatic amines is a direct and efficient approach to the preparation of α,α-disubstituted allylic aryl amines in good yield and with excellent regioselectivity. This method enables the conversion of unactivated primary and secondary amines and the preparation of reverse prenylated indoles in two steps.
J. S. Arnold, G. T. Cizio, H. M. Nguyen, Org. Lett., 2011, 13, 5576-5579.

The use of a carbodicarbene-based pincer ligand scaffold enables a site-selective Rh(I)-catalyzed intermolecular hydroamination of 1,3-dienes with aryl and alkyl amines. Transformations proceed in the presence of 1.0-5.0 mol % Rh complex at 35 - 120 °C; allylic amines are obtained in up to 97% yield and with >98:2 site selectivity.
M. J. Goldfogel, C. C. Roberts, S. J. Meek, J. Am. Chem. Soc., 2014, 136, 6227-6230.

A combination of N-bromoimide and DBU enables allylic amination reactions of alkenes, in which both internal and external nitrogen nucleophiles can be installed directly. Dual activation of NBS or NBP by DBU leads to more electrophilic bromine and more nucleophilic nitrogen atoms simultaneously. This protocol provides a complementary access to allylic amination under mild conditions.
Y. Wei, F. Liang, X. Zhang, Org. Lett., 2013, 15, 5186-5189.

A gold(I)-catalyzed decarboxylative amination of allylic N-tosylcarbamates via base-induced aza-Claisen rearrangement in H2O allows the synthesis of substituted N-tosyl allylic amines in good yield, regioselectivity, and stereoselectivity. This transformation represents an efficient and environmentally benign protocol for the synthesis of N-tosyl allylic amines.
D. Xing, D. Yang, Org. Lett., 2010, 12, 1068-1071.

An oxidative decarboxylation of β,γ-unsaturated carboxylic acids mediated by PhI(OAc)2 gives the corresponding allylic acetates. In addition, a decarboxylative C-N bond formation was achieved. Mechanistic studies suggest an unique reactivity of hypervalent iodine reagents in this ionic oxidative decarboxylation.
K. Kiyokawa, S. Yahata, T. Kojima, S. Minakata, Org. Lett., 2014, 16, 4646-4649.

A rhodium-catalyzed regioselective amination of secondary allylic trichloroacetimidates with unactivated aromatic amines gives N-arylamines in high yields and regioselectivity, favoring the branched amination products. The presence of the trichloroacetimidate leaving group was found to be critical for successful regioselective amination reactions with unactivated aromatic amines.
J. S. Arnold, R. F. Stone, H. M. Nguyen, Org. Lett., 2010, 12, 4580-4583.

Reductive amination of aldehydes and ketones with the InCl3/Et3SiH/MeOH system is highly chemoselective and can be applied to various cyclic, acyclic, aromatic, and aliphatic amines. Functionalities including ester, hydroxyl, carboxylic acid, and olefin are tolerated.
O.-Y. Lee, K.-L. Law, C.-Y. Ho, D. Yang, J. Org. Chem., 2008, 73, 8829-8837.

A direct reaction between carbamates and achiral allylic carbonates to form branched, conveniently protected primary allylic amines with high regioselectivity and enantioselectivity occurs without base in the presence of a metalacyclic iridium catalyst containing a labile ethylene ligand.
D. J. Weix, D. Marković, M. Ueda, J. F. Hartwig, Org. Lett., 2009, 11, 2944-2947.

Hydroamination of substituted allenes with benzyl carbamate catalyzed by (NHC)AuCl and AgOTf in dioxane led to isolation of allylic carbamates in good yield as single regio- and diastereomers.
R. E. Kinder, Z. Zhang, R. A. Widenhoefer, Org. Lett., 2008, 10, 3157-3159.

A protocol for the dehydrative amination of alcohols in water using a water-soluble calix[4]resorcinarene sulfonic acid as a reusable multifunctional catalyst allows an environmentally benign synthesis of benzylic and allylic amines. The aqueous phase containing the catalyst can be readily recycled.
S. Shirakawa, S. Shimizu, Synlett, 2008, 1539-1542.

KF-Celite is an efficient, inexpensive, noncorrosive, and environmentally friendly catalyst for the allylation of anilines. By using only a 1/1.2 stoichiometric ratio of electrophilic reagent to aniline, monoallylated products are obtained in high isolated yields in very short reaction times.
V. Pace, F. Martínez, M. Fernández, J. V. Sinisterra, A. R. Alcántara, Org. Lett., 2007, 9, 2661-2664.

Iridium-catalyzed allylation of potassium trifluoroacetamide or the highly reactive ammonia equivalent lithium di-tert-butyliminodicarboxylate forms a range of conveniently protected, primary, α-branched allylic amines in high yields, high branched-to-linear regioselectivities, and high enantiomeric excess.
M. J. Pouy, A. Leitner, D. J. Weix, S. Ueno, J. F. Hartwig, Org. Lett., 2007, 9, 3949-3952.

A Pd-catalysed termolecular allenylation cascade followed by a Ru catalysed RCM process affords a diverse range of Δ3-aryl/heteroaryl substituted five-seven membered nitrogen and oxygen heterocycles.
H. A. Dondas, B. Clique, B. Cetinkaya, R. Grigg, C. Kilner, J. Morris, V. Sridharan, Tetrahedron, 2005, 61, 10652-10666.

Various allyl carbonates have been converted under Fe catalysis into essentially regio- and stereoisomerically pure allyl amines. Catalytic amounts of piperidinium hydrochloride as a buffer retard catalyst decomposition.
B. Plietker, Angew. Chem. Int. Ed., 2006, 45, 6053-6056.

A catalytic asymmetric synthesis of unprotected secondary allylic amines based on the aza-Claisen rearrangement of N-aryl- and N-alkyl-substituted trifluoroacetimidates has been developed, which provides the targeted products with excellent enantioselectivity.
Z.-q. Xin, D. F. Fischer, R. Peters, Synlett, 2008, 1495-1499.

COP-Cl catalyzes the rearrangement of (E)-allylic trichloroacetimidates to provide transposed allylic trichloroacetamides of high enantiopurity. This practical method for transforming prochiral allylic alcohols to enantioenriched allylic amines offers high functional group compatibility.
C. E. Anderson, L. E. Overman, J. Am. Chem. Soc., 2003, 125, 12412-12413.

Privileged allylic amine structures can be constructed in a regioselective, stereoselective, and diversity-oriented manner by a novel palladium-catalyzed four-component assembly based on allenylboronate platform. A short synthesis of rolipram is also demonstrated.
K. Tonogaki, K. Itami, J.-I. Yoshida, J. Am. Chem. Soc., 2006, 128, 1464-1465.

The synthesis and properties of different planar chiral 1-phosphino-2-sulfenylferrocene ligands are reported. Very high enantioselectivities were obtained in the palladium-catalyzed allylic substitution of 1,3-diphenyl-2-propenyl acetate with dimethyl malonate and nitrogen nucleophiles using readily available tert-butylsulfenyl derivatives.
O. G. Mancheno, J. Priego, S. Cabrera, R. G. Arrayas, T. Llamas, J. C. Carretero, J. Org. Chem., 2003, 68, 3679-3686.

A mild, gold(I)-catalyzed hydroamination of 1,3-dienes is reported. Various carbamates and sulfonamides add to conjugated dienes to affort protected allylic amines in good to high yields.
C. Brouwer, C. He, Angew. Chem. Int. Ed., 2006, 45, 1744-1747.

Bi(OTf)3/Cu(CH3CN)4PF6 efficiently catalyzes an intermolecular 1:1 hydroamination of 1,3-dienes with various carbamates, sulfonamides, and carboxamides to afford allylic amines in good yield.
H. Qin, N. Yamagiwa, S. Matsunaga, M. Shibasaki, J. Am. Chem. Soc., 2006, 128, 1611-1614.

An enantioselective alkoxycarbonylation-amination cascade process of terminal allenes with CO, methanol, and arylamines proceeds under mild conditions (r.t., ambient pressure CO) via oxidative Pd(II) catalysis using a chiral aromatic spiroketal-based diphosphine ligand and a Cu(II) salt as an oxidant to afford various α-methylene-β-arylamino acid esters in good yields with excellent enantioselectivity and high regioselectivity.
J. Liu, Z. Han, X. Wang, Z. Wang, K. Ding, J. Am. Chem. Soc., 2015, 137, 15346-15349.

A direct Fe-catalyzed synthesis of β-alkyl N-aryl aza Baylis-Hillman (ABH) adducts involves the formation of a C–N bond via a nitroso-ene reaction. This is a simple, fast, and best alternate method to overcome the substrate scope limitations of the ABH reaction. Various arylhydroxylamines reacted with esters, aldehydes, ketone, and nitriles to yield the corresponding products in good yields.
S. Murru, A. A. Gallo, R. S. Srivastava, J. Org. Chem., 2012, 77, 7119-7123.

A palladium-catalyzed allylic amination enables an asymmetric synthesis of α,α-disubstituted allylic N-arylamines from highly modular vinyl cyclic carbonates and unactivated aromatic amine nucleophiles. The catalytic process features minimal waste production, high asymmetric induction, and operational simplicity.
A. Cai, W. Guo, L. Martínez-Rodríguez, A. W. Kleij, J. Am. Chem. Soc., 2016, 138, 14194-14197.

A regio- and enantioselective amination of racemic tertiary allylic trichloroacetimidates with a variety of aniline nucleophiles in the presence of a chiral diene-ligated rhodium catalyst is a direct and efficient route to chiral α,α-disubstituted allylic N-arylamines in good yields with very good levels of regio- and enantioselectivity.
J. S. Arnold, H. M. Nguyen, J. Am. Chem. Soc., 2012, 134, 8380-8383.

A highly enantioselective and catalytic vinylation of aldehydes leads to allylic alcohols that are then transformed to the allylic amines via Overman's [3,3]-sigmatropic rearrangement of imidates. Oxidative cleavage of the allylic amines furnishes amino acids in good yields and excellent ee's. The scope and utility of this method are demonstrated by the synthesis of challenging allylic amines and their subsequent transformation to valuable nonproteinogenic amino acids, including both D and L configured (1-adamantyl)glycine.
Y. K. Chen. A. E. Lurain, P. J. Walsh, J. Am. Chem. Soc., 2002, 124, 12225-12231.

3-Pyrroline has been prepared from (Z)-1,4-dichloro-2-butene in three steps in an overall yield of 74%. The Delépine Reaction permitted the monoamination of the substrate in practically quantitative yields. The subsequent ring-closing reaction was less efficient.
S. Brandänge, B. Rodriquez, Synthesis, 1988, 347-348.

The synthesis of isomerically pure allylic amines, including farnesyl amine, is achieved in excellent yields using a modified Gabriel synthesis.
S. E. Sen, S. L. Roach, Synthesis, 1995, 756-758.


Catalytic access to thermodynamically less stable Z-alkenes have relied upon kinetic control of the reaction. A mild and simple orthogonal approach proceeds via photochemically catalyzed isomerization of the thermodynamic E-alkene to the less stable Z-isomer via a photochemical pumping mechanism.
K. Singh, S. J. Staig, J. D. Weaver, J. Am. Chem. Soc., 2014, 136, 5275-5278.