Categories: C-C Bond Formation > Nitrogen-containing molecules > Synthesis of amines >
Synthesis of Homoallylamines
A general and mild CuCl-TBAT-catalyzed allylation of aldehydes, ketones, and imines was developed using allyltrimethoxysilane as the allylating reagent. Mechanism studies indicated that the copper alkoxide, allylfluorodimethoxysilane, and allyltrimethoxysilane are essential to promote the reaction efficiently.
S. Yamasaki, K. Fujii, R. Wada, M. Kanai, M. Shibasaki, J. Am. Chem. Soc., 2002, 124, 6536-6537.
Stoichiometric KOtBu in THF enables an efficient transition metal-free approach for the generation of N-unsubstituted imines from azides. Trapping with allyl nucleophile provides N-unsubstituted homoallylic amines. Further, an enantio- and diastereoselective synthesis of homoallylic amines from benzyl azide has also been exemplified.
S. Pramanik, R. R. Reddy, P. Ghorai, J. Org. Chem., 2015, 80, 3656-3663.
Triallylborane-amine adducts can be used as stoichiometric allylating agents for efficient aminoallylation reactions of carbonyl compounds in methanol. Moreover, copper catalysis enables a diastereoselective allylation of Ellman’s imine.
N. Y. Kuznetsov, R. M. Tikhov, T. V. Strelkova, Y. N. Bubnov, Org. Lett., 2018, 20, 3549-3552.
A Rh-catalyzed asymmetric allylation of aliphatic aldimines provides optically active 1-alkyl homoallylic amines in good yields and very good ee under mild, aqueous reaction conditions. The preparation of indolizidine and piperidine alkaloids demonstrates the usefulness of this method.
W.-S. Li, T.-S. Kuo, M.-C. Hsieh, M.-K. Tsai, P.-Y. Wu, H.-L. Wu, Org. Lett., 2020, 22, 5675-5679.
Sulfonimines derived from nonenolizable aldehydes can be effectively allylated to the corresponding homoallylic sulfonamides with allylic bromides promoted by indium or zinc. The stereoselectivity and regioselectivity of the reactions were examined.
W. Lu, T. H. Chan, J. Org. Chem., 2000, 65, 8589-8594.
A combination of a photoredox and a palladium catalyst catalyzes a dehydrative coupling reaction of alkyl amines with allylic alcohols to provide a range of homoallylic amines.
Y. Masuda, M. Ito, M. Murakami, Org. Lett., 2020, 22, 4467-4470.
BF3·Et2O promotes an interrupted Schmidt rearrangement/Hosomi-Sakurai reaction of N-tosyl vinyl azides via denitrogenative fragmentation, generation of a stabilized carbocation, which further undergoes nucleophilic addition by allyl/propargylsilanes for C-C bond formation. The reaction provides various homoallylic/allenylic amines in good yields under mild reaction conditions with well-defined functional-group tolerance.
G. Fang, Z. Liu, S. Cao, H. Yuan, J. Zhang, L. Pan, Org. Lett., 2018, 20, 7113-7116.
A palladium complex catalyzes two transformations in one pot: formation of allylsilane from allyl trifluoroacetate using hexamethyldisilane and subsequent imine allylation. A three-component reaction was developed where preformed imines were replaced with aldehydes and anisidine. Under these reaction conditions various aldehydes react smoothly to afford homoallylic amines.
R. E. Grote, E. R. Jarvo, Org. Lett., 2009, 11, 485-488.
An asymmetric Rh-catalyzed 1,2-allylation of N-Ts- and N-Ns-aldimines with potassium allyltrifluoroborates generates enantioenriched homoallylic amines in very good yields with very good enantioselectivities. Using subsituted allyltrifluoroborates, high diastereoselectivity is achieved. Reactions of both potassium (E)- and (Z)-crotyltrifluoroborates provide the same diastereomer.
P. F. Chiang, W.-S. Li, J.-H. Jiang, T.-S. Kuo, P.-Y. Wu, H.-L. Wu, Org. Lett., 2018, 20, 158-161.
Readily accessible N-(aryloxy)imines undergo efficient allylation to afford a wide range of homoallylic primary amines following hydrolytic workup. Deprotonation of N-(aryloxy)imines generates a delocalized 2-azaallyl anion-type nucleophile that engages in dearomative unselective allylation followed by [1,3]- or concerted [3,3]-sigmatropic shifts to provide the desired products.
L. M. Mori-Quiroz, S. S. Londhe, M. D. Clift, J. Org. Chem., 2020, 85, 14827-14846.
An enantioselective synthesis of homoallylamides through reactions of stable and easily accessible (pinacolato)allylborons with aryl-, heteroaryl-, alkyl-, or alkenyl-substituted N-phosphinoylimines is promoted by 1-5 mol % of readily accessible NHC-Cu complexes, derived from C1-symmetric imidazolinium salts. Allyl additions deliver the desired products in very good yield and enantiomeric ratio.
E. M. Vieira, M. L. Snapper, A. H. Hoveyda, J. Am. Chem. Soc., 2011, 133, 3332-3335.
An iridium-catalyzed asymmetric umpolung allylation of imines provides 1,4-disubstituted homoallylic amines via a sequence involving an intermolecular regioselective allylation of 2-azaallyl anions followed by a 2-aza-Cope rearrangement. The reaction utilizes easily available reagents and catalysts, tolerates a substantial scope of substrates, and readily leads to various enantioenriched, 1,4-disubstituted homoallylic primary amines.
J. Liu, C.-G. Cao, H.-B. Sun, X. Zhang, D. Niu, J. Am. Chem. Soc., 2016, 138, 13103-13106.
The catalytic use of a sodium amide enables a formal allylic C(sp3)-H bond activation of alkenes under mild conditions. Subsequent C-C bond formations with imines have proceeded in high yields with complete regioselectivity and excellent geometric selectivity.
W. Bao, H. Kossen, U. Schneider, J. Am. Chem. Soc., 2017, 139, 4362-4365.
A highly α-regioselective prenylation of imines enables the conversion a wide range of substrates including N- and C-aryl aldimines, N-alkyl aldimines, C-alkyl aldimines, and N- and C-aryl ketimines. The approach uses prenyl bromide as prenyl source and inexpensive zinc as mediator as well as environmentally benign 1,3-dimethyl-2-imidazolidinone (DMI) as solvent.
L.-M. Zhao, S.-Q. Zhang, H.-S. Jin, L.-J. Wan, F. Dou, Org. Lett., 2012, 14, 886-889.
Aromatic aldehydes can be converted to α-amino anion equivalents via amination with 2,2-diphenylglycine and subsequent decarboxylation. These in situ generated α-imino anions are highly reactive for Pd-catalyzed allylation to give homoallylic amines in high yields with excellent regioselectivity.
L. Ding, J. Chen, Y. Hu, J. Xu, X. Gong, D. Xu, B. Zhao, H. Li, Org. Lett., 2014, 16, 720-723.
A highly efficient three-component coupling reaction between thioformamides and organolithium and Grignard reagents was developed. The generality of the process has been demonstrated by using various combinations of reactants and reagents.
T. Murai, F. Asai, J. Am. Chem. Soc., 2007, 129, 780-781.
A mild and chemoselective double allylboration of nitriles and acid anhydrides to form bis-allyl amines and esters, respectively, can be achieved through the use of potassium allyltrifluoroborate in the presence of boron trifluoride etherate at room temperature. The reaction with an operationally stable and robust potassium organotrifluoroborate reagent avoids the use of metals.
T. R. Ramadhar, J. Bansagi, R. A. Batey, J. Org. Chem., 2013, 78, 1216-1221.
Homoallylic α-amino esters and amines were prepared via a Pd(II)-catalyzed coupling of 1,2-nonadiene and boronic acids with ethyl iminoacetate or aliphatic, aromatic, and heteroaromatic imines.
C. D. Hopkins, H. C. Malinakova, Org. Lett., 2006, 8, 5971-5974.
The combination of dirhodium(II)/Xantphos catalyzes a three-component reaction of readily accessible amines, diazo compounds, and allylic compounds to afford various architecturally complex and functionally diverse α-quaternary α-amino acid derivatives in good yields with high atom and step economy.
B. Lu, X. Liang, J. Zhang, Z. Wang, Q. Peng, X. Wang, J. Am. Chem. Soc., 2021, 143, 11799-11810.
An asymmetric vinylogous Mannich reaction of α,α-dicyanoolefins and N-Boc aldimines is promoted by a simple chiral bifunctional thiourea-tertiary amine organocatalyst. The reaction was highly efficient, regio-, and stereoselective at room temperature for a broad range of substrates.
T.-Y. Liu, H.-L. Cui, J. Long, B.-J. Li, Y. Wu, L.-S. Ding, Y.-C. Chen, J. Am. Chem. Soc., 2007, 129, 1878-1879.
Pd-catalyzed asymmetric allylic alkylation of nitroalkanes and monosubstituted allylic substrates affords products with two adjacent chiral centers in excellent regio-, diastereo-, and enantioselectivities. Products can be transformed to optically active homoallylamines, 2,3-disubstituted tetrahydropyridines, and α,β-disubstituted amino acid derivatives.
X.-F. Yang, W.-H. Yu, C.-H. Ding, Q.-P. Ding, S.-L. Wan, X.-L. Hou, L.-X. Dai, P.-J. Wang, J. Org. Chem., 2013, 78, 6503-6509.