1.Consecutive Cycloaddition/S(N)Ar/Reduction/Cyclization/Oxidation Sequences: A Copper-Catalyzed Multicomponent Synthesis of Fused N-Heterocycles.
Jia FC, Xu C, Zhou ZW, Cai Q, Li DK, Wu AX1. Org Lett. 2015 Jun 5;17(11):2820-3. doi: 10.1021/acs.orglett.5b01242. Epub 2015 May 21.
A highly efficient multicomponent domino protocol has been developed for the synthesis of 5-phenyl-[1,2,3]triazolo[1,5-c]quinazolines from simple and readily available (E)-1-bromo-2-(2-nitrovinyl)benzenes, aldehydes, and sodium azide. This elegant domino process involved consecutive [3 + 2] cycloaddition, copper-catalyzed S(N)Ar, reduction, cyclization, and oxidation sequences. Notably, sodium azide acted as a dual nitrogen source in the construction of this novel fused N-heterocycle.
2.Asymmetric synthesis of 3-substituted tetrahydro-2-benzazepines.
Quick MP1, Fröhlich R, Schepmann D, Wünsch B. Org Biomol Chem. 2015 Jul 14;13(26):7265-81. doi: 10.1039/c5ob00731c. Epub 2015 Jun 9.
The enantiomerically and diastereomerically pure tricyclic oxazolidine cis-10 was prepared in a five step synthesis starting with 1-bromo-2-iodobenzene. Me3SiCN and allylSiMe3 reacted with cis-10 in the presence of TiCl4 to form the nitrile (3S)-11 and the allyl derivative (3S)-12 with high diastereoselectivity. The hydrogenolytic removal of the chiral auxiliary failed, since the endocyclic benzyl-N-bond was cleaved simultaneously. Therefore the N-(hydroxyethyl)amide of (3S)-12 was transformed into the enamide 27, which was hydrolyzed to afford the secondary amide 28. The enamide strategy to remove the chiral auxiliary from (3S)-11 led to complete racemization due to fast deprotonation in α-position of the cyano moiety. Two pairs of enantiomers 30a-b/ent-30a-b with prototypical σ substituents at the N-atom were prepared. The low σ1 affinity of the tetrahydro-2-benzazepines (ent-30b, Ki = 407 nM) is attributed to the short distance between the two lipophilic aromatic moieties.
3.Selective Access to 3-Cyano-1H-indoles, 9H-Pyrimido[4,5-b]indoles, or 9H-Pyrido[2,3-b]indoles through Copper-Catalyzed One-Pot Multicomponent Cascade Reactions.
Li B1, Guo S1, Zhang J1, Zhang X1, Fan X1. J Org Chem. 2015 Jun 5;80(11):5444-56. doi: 10.1021/acs.joc.5b00239. Epub 2015 May 18.
Novel and selective synthetic approaches toward indole derivatives via copper-catalyzed one-pot multicomponent cascade reactions of 1-bromo-2-(2,2-dibromovinyl)benzenes with aldehydes and aqueous ammonia are presented. Intriguingly, the concentration of ammonia, the molar ratio of reagents, and the structural features of the aldehyde substrate serve as key factors in controlling the selective formation of 3-cyano-1H-indoles, 9H-pyrimido[4,5-b]indoles, or 9H-pyrido[2,3-b]indoles. Compared with literature procedures, the synthetic approaches reported herein have advantages such as readily available starting materials, mild reaction conditions, and divergent reaction patterns toward different products with easily tunable selectivity.
4.Amino-functionalized (meth)acryl polymers by use of a solvent-polarity sensitive protecting group (Br-t-BOC).
Ritter H1, Tabatabai M1, Herrmann M1. Beilstein J Org Chem. 2016 Feb 10;12:245-52. doi: 10.3762/bjoc.12.26. eCollection 2016.
We describe the synthesis of bromo-tert-butyloxycarbonyl (Br-t-BOC)-amino-protected monomers 2-((1-bromo-2-methylpropan-2-yl)oxycarbonylamino)ethyl (meth)acrylate 3a,b. For this purpose, 2-isocyanatoethyl (meth)acrylate 1a,b was reacted with 1-bromo-2-methylpropan-2-ol (2a). The free radical polymerization of (Br-t-BOC)-aminoethyl (meth)acrylates 3a,b yielded poly((Br-t-BOC)-aminoethyl (meth)acrylate) 6a,b bearing protected amino side groups. The subsequent solvolysis of the Br-t-BOC function led to the new polymers poly(2-aminoethyl (meth)acrylate) 8a,b with protonated free amino groups. The monomers and the resulting polymers were thoroughly characterized by (1)H NMR, IR, GPC and DSC methods. The kinetics of the deprotection step was followed by (1)H NMR spectroscopy. The solvent polarity and neighboring group effects on the kinetics of deprotection are discussed.