The catalytic asymmetric 1,3-dipolar cycloaddition (1,3-DC) has now become one of the most established methods for the stereoselective synthesis of five-membered heterocycles having contiguous stereogenic centers, concurrent with the development of chiral Lewis acids and organocatalysts.[1] As a reaction mode for 1,3-DCs, normal-electron-demand (NED) 1,3-DCs proceed by the interaction of a catalytically activated LUMO of electron-deficient alkenes with the HOMO of the 1,3-dipoles; alternatively, the inverse-electron-demand (IED) 1,3-DCs are facilitated by the interaction of the LUMO of an acid-activated 1,3-dipole and the HOMO of electron-rich alkenes. Although synchronous development of both features in the realm of asymmetric catalysis would be highly desirable to produce a diverse array of cycloadducts, IED 1,3-DCs are far less developed to date and remain a challenge in contrast to the sophistication and diversification of their NED counterparts. [2, 3, 5h-j, 11a] We recently succeeded in shedding light on the as of yet unexplored utility of C,N-cyclic azomethine imines 1 in the titanium/binolate catalyzed NED 1,3-DC using enals as dipolarophiles (Scheme 1). [4,5] As the next step of the study, we set out to investigate the asymmetric IED 1,3-DC of these 1,3-dipoles, [6] coupled with the fact that the related methods for catalytic asymmetric di-and tetrahydroisoquinoline syntheses by the nucleophilic addition to (dihydro)isoquinoline derivatives are still far from established in terms of the generality and selectivity. [7] We report herein the investigation toward this end using vinyl ether as a conventional electron-rich dipolarophile and the axially chiral dicarboxylic acid originally developed in our group as a chiral Brønsted acid catalyst, [8] which succeeded in attaining a remarkably broad substrate scope to give a variety of C1-chiral tetrahydroisoquinolines with excellent enantioselectivity irrespective of the position and electronic nature of the substituents. In addition, unique Lewis acid catalyzed functionalizations of the cycloadducts were disclosed in which tetrahydroisoquinolines with additional chiral stereocenter at the C1 side chain could be generated stereoselectively. This accomplishment prompted us to introduce a new concept called the IED umpolung 1,3-DC, which gives cycloadducts regioisomeric to the products of the previously reported titanium/binolate-catalyzed NED 1,3-DC starting from the same enals. This tactic could be realized by the umpolung nature of enals imposed by the formation of the corresponding N,N-dialkylhydrazones, [9] also known as vinylogous azaenamines (Scheme 1).A clue to the development of asymmetric IED 1,3-DCs of C,N-cyclic azomethine imines with vinyl ether was provided from our early observation that these 1,3-dipoles easily form stable protonated salts in the presence of a hydrobromic acid.[4] This fact naturally led us to the use of a chiral Brønsted acid, which has recently emerged as a powerful tool for numerous stereoselective organic transformations....
Upon heating with p-chloranil in CHCl 3 , 5,10,15-tris(pentafluorophenyl)corrole (1H) underwent regioselective oxidative coupling reaction at the 3,3¤-position to give dimer 2H and trimer 3H. Oxidation of 2H with p-fluoranil gave tetramer 4H and hexamer 6H. The crystal structures have been revealed for 2H, cobalt(III) complexed trimer 3Co¢py 6 , and tetramer 4Co¢py 8 .In the last decade, we have explored a variety of porphyrin arrays on the basis of Ag(I)-promoted oxidative mesomeso coupling reaction of 5,15-diaryl Zn(II)porphyrin, 19 which include extremely long linear arrays, 2 helical arrays, 3 threedimensional windmill arrays, 4 cyclic arrays, 5 supramolecular porphyrin boxes, 6 highly conjugated porphyrin tapes, 7 and an antiaromatic porphyrin sheet. 8 As such, this simple synthetic method that allows a direct porphyrinporphyrin connection has been demonstrated quite useful for construction of novel multiporphyrinic architectures of attractive properties and functions. 9A similar synthetic method that permits a direct corrole corrole linkage should have analogous synthetic potentials and thus be highly desirable. Corrole, a one-meso-carbon-contracted porphyrin analogue bearing a direct pyrrolepyrrole linkage, is a unique 18³ aromatic macrocycle stabilizing higher oxidation states of some metal ions.10 The chemistry of corroles has recently been boosted by the development of facile synthetic methods of 5,10,15-triaryl-substituted corroles, 1113 but still remains rather unexplored as compared to those of porphyrins. In particular, studies on covalently linked corrole oligomers have been limited compared with an extensive lineup of porphyrin counterparts. Guilard et al. reported a series of face-to-face porphyrincorrole hybrids as well as corrole dimers as a promising model of a four-electron reduction catalyst of oxygen to water, 14 and Smith et al. reported aromatic-bridged corrole dimers and corroleporphyrin hybrids.15 Gross et al. reported that directly 3,3¤-linked corrole dimers 2a and 2b were formed during the metalation of 5,10,15-tris(pentafluorophenyl)corrole 1H with Co(OAc) 2 and triphenylphosphine or Cu(OAc) 2 ¢H 2 O (Chart 1).16 Cavaleiro et al. found that corrole free base 1H underwent oxidative coupling reaction in a low yield. 17 We explored a rational synthetic route to doubly ¢,¢-linked corrole dimers through a singly 2,2¤-linked corrole dimer on the basis of Pd-catalyzed oxidative coupling reaction of 2-borylated corrole followed by oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ).18 Quite unexpectedly, an oxidized form of doubly ¢,¢-linked corrole dimer exists as a neutral biradical that is stable under air and water.Here, we wish to report a very simple yet effective synthetic method for direct coupling of 1H. Results and DiscussionCorrole 1H has been most frequently used, due to its easy availability and chemical stability. Synthesis of 1H has been achieved by solvent-free protocols 11,19 or via a dipyrromethane route 13 and a tetrapyrrane route. 20 In all these procedures, ...
Highly stereoselective 1,3-dipolar cycloadditions of methacrolein and nitrones could be realized by the use of bis-titanium chiral Lewis acid catalyst. Key to the success is the introduction of bulky N-substituent on nitrone to attenuate the undesired Lewis acid-nitrone complexation.
The catalytic asymmetric 1,3-dipolar cycloaddition (1,3-DC) has now become one of the most established methods for the stereoselective synthesis of five-membered heterocycles having contiguous stereogenic centers, concurrent with the development of chiral Lewis acids and organocatalysts. [1] As a reaction mode for 1,3-DCs, normal-electron-demand (NED) 1,3-DCs proceed by the interaction of a catalytically activated LUMO of electron-deficient alkenes with the HOMO of the 1,3-dipoles; alternatively, the inverse-electron-demand (IED) 1,3-DCs are facilitated by the interaction of the LUMO of an acid-activated 1,3-dipole and the HOMO of electron-rich alkenes. Although synchronous development of both features in the realm of asymmetric catalysis would be highly desirable to produce a diverse array of cycloadducts, IED 1,3-DCs are far less developed to date and remain a challenge in contrast to the sophistication and diversification of their NED counterparts. [2, 3, 5h-j, 11a] We recently succeeded in shedding light on the as of yet unexplored utility of C,N-cyclic azomethine imines 1 in the titanium/binolate catalyzed NED 1,3-DC using enals as dipolarophiles (Scheme 1). [4,5] As the next step of the study, we set out to investigate the asymmetric IED 1,3-DC of these 1,3-dipoles, [6] coupled with the fact that the related methods for catalytic asymmetric di-and tetrahydroisoquinoline syntheses by the nucleophilic addition to (dihydro)isoquinoline derivatives are still far from established in terms of the generality and selectivity. [7] We report herein the investigation toward this end using vinyl ether as a conventional electron-rich dipolarophile and the axially chiral dicarboxylic acid originally developed in our group as a chiral Brønsted acid catalyst, [8] which succeeded in attaining a remarkably broad substrate scope to give a variety of C1-chiral tetrahydroisoquinolines with excellent enantioselectivity irrespective of the position and electronic nature of the substituents. In addition, unique Lewis acid catalyzed functionalizations of the cycloadducts were disclosed in which tetrahydroisoquinolines with additional chiral stereocenter at the C1 side chain could be generated stereoselectively. This accomplishment prompted us to introduce a new concept called the IED umpolung 1,3-DC, which gives cycloadducts regioisomeric to the products of the previously reported titanium/binolate-catalyzed NED 1,3-DC starting from the same enals. This tactic could be realized by the umpolung nature of enals imposed by the formation of the corresponding N,N-dialkylhydrazones, [9] also known as vinylogous azaenamines (Scheme 1).A clue to the development of asymmetric IED 1,3-DCs of C,N-cyclic azomethine imines with vinyl ether was provided from our early observation that these 1,3-dipoles easily form stable protonated salts in the presence of a hydrobromic acid. [4] This fact naturally led us to the use of a chiral Brønsted acid, which has recently emerged as a powerful tool for numerous stereoselective organic transformations....
General Information. Infrared (IR) spectra were recorded on a Shimadzu IRPrestige-21 spectrometer. 1 H NMR spectra were measured on a JEOL JNM-FX400 (400 MHz) spectrometer. Data were reported as follows: chemical shifts in ppm from tetramethylsilane as an internal standard in CDCl 3 , integration, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad), and coupling constants (Hz). 13 C NMR spectra were measured on a JEOL JNM-FX400 (100 MHz) spectrometer with complete proton decoupling. Chemical shifts were reported in ppm from the residual solvent as an internal standard. High performance liquid chromatography (HPLC) was performed on Shimadzu 10A instruments at 254 nm using 4.6 mm x 25 cm Daicel Chiral Coulmns. High-resolution mass spectra (HRMS) were performed on Brucker microTOF. Optical rotations were measured on a JASCO DIP-1000 digital polarimeter. For thin layer chromatography (TLC) analysis throughout this work, Merck precoated TLC plates (silica gel 60 GF 254 , 0.25 mm) were used. The products were purified by flash column chromatography silica gel 60 (Merck, 230-400 mesh) or preparative thin layer chromatography silica gel (Merck, PLC 60 F 254 . 0.5 mm).In experiments requiring dry solvent, CH 2 Cl 2 , toluene and THF were purchased from Kanto Chemical Co. Inc. as "Dehydrated" and further purified by passing through neutral alumina under nitrogen atmosphere. Enals were distilled prior to use. Other commercially available reagents were used as received.The relative and absolute configuration of 2 and the relative configuration of 6 were unambiguously assigned by X-ray crystallographic analysis of 2h, 6c', 6f' and 6i'. The stereochemistries of other cycloadducts were tentatively assigned by analogy. Br CHO 2-(2-Bromoethyl)-3-methylbenzaldehydePrepared with 1-methoxy-5-methylisochroman (1.05 g, 5.86 mmol), Bu 4 NBr (1.89 g, 5.86 mmol) and TMSBr (1.55 mL, 11.7 mmol). The crude material was purified by column chromatography on silica gel (eluting with hexane/CH 2 Cl 2 = 3:1) to give the title compound as a colorless oil (9.39 g, 4.13 mmol, 71% yield).
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