Stereoselective synthesis of atropisomeric korupensamines A and B utilizing planar chiral arene chromium complex

Naphthyl tetrahydroisoquinoline alkaloids, atropisomeric korupensamines A and B and ent-korupensamine B, were synthesized by syn-selective cross-coupling of a planar chiral arene chromium complex with naphthylboronic acid and subsequent axial isomerization or tricarbonylchromium migration to the inverted arene face as a key step. Palladium(0)-catalyzed cross-coupling of planar chiral arene chromium complex 12 with naphthylboronic acid 9 gave syn-biaryl coupling product 13. syn-Biaryl chromium complex 13 was heated in 1:1 mixture of di-n-butyl ether and 1,2-dichloroethane to give a face-inverted anti-biaryl chromium complex 14 without axial isomerization. Korupensamine A was synthesized from the syn-biaryl chromium complex 13 via o-formyl syn-biaryl chromium complex 10, and ent-korupensamine B was prepared from the face-inverted anti-biaryl chromium complex 14. On the other hand, difluoro-substituted syn-biaryl chromium complex 40 with a formyl group afforded anti-biaryl chromium complex 41 containing a rotated central bond by heating in xylene. The chromium-complexed fluorine atom was easily substituted with an isopropoxy group by nucleophilic substitution. Use of these reactions allowed (+)-2-bromo-3,5-difluorobenzaldehyde chromium complex (37) as a single chiral source to be converted to atropisomeric korupensamines A and B, respectively.     

Stereoselective synthesis of both enantiomers of N-aryl indoles with axially chiral N-C bonds

N-Aryl indoles with axially chiral N-C bonds were synthesized by stereoselective nucleophilic aromatic substitution reactions of planar chiral tricarbonyl(2,6-disubstituted-1-fluorobenzene)chromium complexes. The stereochemistry of the products is highly dependent on the position of the substituent in the indole. When indoles devoid of a substituent at the 2-position were used, N-aryl indole chromium complexes having anti orientation with respect to the tricarbonylchromium fragment were obtained diastereoselectively. In contrast, 2-substituted indoles gave the N-aryl indoles with syn orientation between the tricarbonylchromium fragment and the benzene ring of the indole. These results demonstrate that we have succeeded in synthesizing both enantiomers of N-aryl indoles utilizing an identical planar chiral arene chromium complex.     

Asymmetric synthesis of axially chiral benzamides and anilides utilizing planar chiral arene chromium complexes

Optically active axially chiral 2,6-disubstituted benzamides and anilides were stereoselectively prepared by utilizing planar chiral (arene)chromium complexes. Nucleophilic addition to enantiomerically pure planar chiral tricarbonyl(N,N-diethyl-2-methyl-6-formyl- (or 6-acyl)benzamide)chromium complex gave axially chiral 2-methyl-6-substituted N,N-diethyl benzamide chromium complexes with high selectivity. An alternative method for the preparation of axial chiral benzamides or anilides is an enantiotopic lithiation at the benzylic methyl of prochiral tricarbonylchromium complexes of N,N-diethyl-2,6-dimethylbenzamide and N-methyl-N-acyl-2,6-dimethylaniline with a chiral lithium amide followed by electrophilic substitution. The resulting axially chiral chromium-complexed benzamides and anilides were oxidized in air to give chromium-free axially chiral benzamides and anilides in enantiomerically enriched form without axial bond rotation at room temperature.     

Stereoselective synthesis of axially chiral N-C bonds in N-aryl indoles

[reaction: see text] N-Aryl indoles with axially chiral N-C bonds were synthesized by stereoselective nucleophilic aromatic substitution reactions of planar chiral arene chromium complexes. Stereoselective chromium tricarbonyl migration was achieved in the sterically hindered N-aryl indole chromium complex by refluxing in toluene.     

Gold(I)-catalyzed asymmetric synthesis of planar chiral arene chromium complexes

Gold(I)-catalyzed asymmetric cyclization of 1,3-dihydroxymethyl-2-alkynylbenzene chromium complexes gave planar chiral isochromene chromium complexes with high enantioselectivity. Enantiomeric excess of the cyclization products was largely affected by a combination of axially chiral diphosphine(AuCl)(2) precatalysts and silver salts. A system of segphos(AuCl)(2) with AgBF(4) resulted in the formation of the corresponding antipode.     

Circular dichroism of optically active organometallic derivatives of fullerenes C<Subscript>60</Subscript> and C<Subscript>70</Subscript>

Palladium and platinum complexes of fulleienes C₆₀ and C₇₀ containing the axially chiral ligand (—)-BITIANP (BITIANP is 2,2’-bis(diphenylphosphino)-3,3’-bi(benzo[b]thiophene)) and pynolidino[60]fullerene bearing a planar chiral organometallic π-complex substituent in the heteiocyclic ring were studied by circular dichroism (CD) spectroscopy.     

Simultaneous Induction of Axial and Planar Chirality in Arene–Chromium Complexes by Molybdenum‐Catalyzed Enantioselective Ring‐Closing Metathesis

The molybdenum‐catalyzed asymmetric ring‐closing metathesis of the various C_s‐symmetric (π‐arene)chromium substrates provides the corresponding bridged planar‐chiral (π‐arene)chromium complexes in excellent yields with up to >99 % ee. With a bulky and unsymmetrical substituent, such as N‐indolyl or 1‐naphthyl, at the 2‐positions of the η⁶‐1,3‐diisopropenylbenzene ligands, both biaryl‐based axial chirality and π‐arene‐based planar chirality are simultaneously induced in the products. The axial chirality is retained even after the removal of the dicarbonylchromium fragment, and the chiral biaryl/heterobiaryl compounds are obtained with complete retention of the enantiopurity.     

Asymmetric synthesis of anti- and syn-beta-amino alcohols by reductive cross-coupling of transition metal-coordinated planar chiral arylaldehydes with aldimines

Samarium iodide-mediated cross-coupling of N-tosyl ferrocenylideneamine with planar chiral ferrocenecarboxaldehydes or benzaldehyde chromium complexes gave diastereoselectively the corresponding anti-beta-amino alcohol derivatives in good yields, while N-tosyl benzylideneamine produced syn-beta-amino alcohols by coupling with planar chiral arylaldehydes. Dynamic kinetic resolution of a configurationally equilibrated reactive species generated from achiral N-tosyl ferrocenilideneamine and benzylideneamine by reduction with samarium iodide was observed in the cross-coupling with planar chiral arylaldehydes giving both antipodes of beta-amino alcohols depending on the planar chirality. The obtained anti-beta-amino alcohol with the ferrocene ring was utilized as a chiral ligand for catalytic asymmetric reduction of acetophenone.     

Asymmetric synthesis of beta-amino alcohols by reductive cross-coupling of benzylideneamine with planar chiral benzaldehydes

[reaction: see text] Samarium iodide mediated reductive cross-coupling of N-tosyl benzylideneamine with benzaldehydes or the corresponding chromium complexes gave syn-beta-amino alcohol derivatives. A dynamic kinetic resolution of a configurationally equilibrated reactive species occurred in the cross-coupling with planar chiral benzaldehyde chromium complexes.     

Reaction of α,β-unsaturated Fischer carbene complexes with allyl alkoxide

Optically enriched homo-binuclear Fischer chromium carbene complexes with planar chiral arene chromium complexes gave α-allyl β-arylpropionates up to 97% ee by reaction with allyl alkoxide and subsequent photo-oxidative demetalation. The chiral hetero-binuclear tungsten carbene complexes afforded anti α-allyl β-hydroxy β-arylpropionates as a major product up to 92/8 dr by the same reaction sequence. High diastereoselectivity in these reactions is contributed to the planar chirality of the arene chromium complex, even though the reaction was carried out under vigorous basic media. The reaction products, α-allyl β-arylpropionates were derived by 1,3-M(CO)₅ shift and subsequent [3,3]-sigmatropic rearrangement. Also, the corresponding chromium-uncomplexed α,β-unsaturated Fischer carbene complexes afforded α-allyl β-arylpropionates under the same conditions. Formation of β-allyl β-arylpropionates via 1,2-M(CO)₅ shift followed by [3,4]-sigmatropic rearrangement was not observed in both reactions of chromium-coordinated and the corresponding chromium-uncoordinated α,β-unsaturated Fischer carbene complexes with allyl alkoxide in the presence of base.     

Stereoselective [3+2+2] cycloaddition utilizing optically active binuclear Fischer carbene complexes with alkynes

The reaction of optically active α,β-unsaturated binuclear Fischer carbene complexes with alkynes gave planar chiral cycloheptatriene chromium complexes via [3+2+2] cycloaddition with high diastereoselectivity.     

Synthesis and use in palladium-catalyzed asymmetric allylic alkylation of new planar chiral chromium complexes of 1,2-disubstituted arenes having pyridine and aryl phosphine groups

Optically active (1,2-disubstituted arene)chromium tricarbonyl complexes 4–7 having pyridine and aryl phosphorus groups were synthesized from (o-disubstituted benzaldehyde)tricarbonylchromium. These chromium complexes have been used as chiral ligands in the asymmetric allylic alkylation of rac-1,3-diphenyl-2-propenyl acetate 8 catalyzed by (η³-allyl)palladium complex. The enantioselectivity increases as the number of electron-withdrawing substituents in the aryl phosphine increases. Significant solvent effects on the enantioselectivity were observed for 4 and 7. By the judicious choice of the planar chiral ligand, high enantioselectivities (90% R, 93% S at 0°C) were observed.     

Asymmetric Synthesis of Axially Chiral Anilides by Enantiotopic Lithiation of Tricarbonyl(N-methyl-N-acyl-2,6-dimethylanilide)chromium Complex

Axially chiral N-methylanilides were synthesized by enantioselective lithiation of prochiral tricarbonyl(N-methyl-N-pivaloyl-2,6-dimethylaniline)chromium (1) with the lithium amide of the 4-methylpiperazinylethylamine derivative 13 followed by electrophilic quenching up to 97% ee in good yields. The resulting axially chiral chromium-complexd anilides 2 were oxidized under air to give the axially chiral anilides 14 in enantiomerically active form without axial bond rotation at room temperature.     

Chromium arene complexes in organic synthesis

The complexation of an arene to a chromium tricarbonyl unit changes its chemical behavior, giving rise to unprecedented transformations. The electron-withdrawing effect of the unit allows efficient nucleophilic attack (S(N)Ar and dearomatization reactions), stabilizes negative charges in benzylic positions and activates C(Ar)-halogen bonds for cross-coupling reactions. In addition, the Cr(CO)(3) moiety exerts great facial control so it can be used as an auxiliary that can easily be removed. The 1,2- and 1,3-unsymmetrically disubstituted complexes are planar chiral and there are various ways to prepare them in enantiomerically pure form. Planar chiral chromium complexes are becoming useful intermediates and ligands for asymmetric catalysis. This mature field of organometallic chemistry has given rise to several synthetic applications of chromium arene complexes in the synthesis of natural products. This chemistry is overviewed in this tutorial review, giving special attention to the most recent and outstanding contributions in the area.     

Coordination properties of axially unfixed chiral dipyridine ligands towards metal and ammonium ions

New chiral dipyridine ligands with an axially unfixed 1,1′-biphenyl bridge were prepared via homocoupling of bromophenyl pyridines. The conformeric ratios of the free ligands in solution and their coordination properties towards metal ions were studied by NMR spectroscopy. X-Ray crystallography of the silver(I) and copper(I) complexes showed 1:1 metal to ligand complexes and S planar chirality. Interestingly, the biphenyl ligands show a 1:2 stepwise binding towards most ammonium ions tested with strong fluorescence enhancement, but a selectively 1:1 binding towards l-ornithine methyl ester hydrochloride with no fluorescence enhancement.     

Asymmetric synthesis of axially chiral benzamides and anilides by enantiotopic lithiation of prochiral arene chromium complexes

Axially chiral benzamides and anilides were prepared by enantiotopic lithiation at the distinguished benzylic methyl of prochiral tricarbonylchromium complexes of N,N-diethyl 2,6-dimethylbenzamide (1) and N-methyl-N-acyl 2,6-dimethylaniline (14 and 21) with a chiral lithium amide base followed by electrophilic substitution in good yields with high optical purity. The resulting axially chiral chromium-complexed benzamides and anilides were oxidized under air to give chromium-free axially chiral benzamides and anilides in an enantiomerically active form without axial bond rotation at room temperature.     

Gold(I)-catalyzed stereoselective cyclization of ortho alkynyl benzaldehyde chromium complexes with nucleophiles

Gold(I)-catalyzed cyclization of o-alkynyl benzaldehyde chromium complexes gave stereoselectively 1-anti- and syn-functionalized 1H-isochromene chromium complexes, respectively, depending on the nature of nucleophiles. Enantiomerically pure trans- and cis-1,3-dimethylisochromans were stereoselectively prepared from a single planar chiral o-(1-propynyl)benzaldehyde chromium complex.     

Inducing Axial Chirality in a Supramolecular Catalyst

A new type of ligand, which is able to form axially chiral, supramolecular complexes was designed using DFT calculations. Two chiral monomers, each featuring a covalently bound chiral auxiliary, form a bidentate phosphine ligand with a twisted, hydrogen‐bonded backbone upon coordination to a transition metal center which results in two diastereomeric, tropos complexes. The ratio of the diastereomers in solution is very temperature‐ and solvent‐dependent. Rhodium and platinum complexes were analyzed through a combination of NMR studies, ESI‐MS measurements, as well as UV‐VIS and circular dichroism spectroscopy. The chiral self‐organized ligands were evaluated in the rhodium‐catalyzed asymmetric hydrogenation of α‐dehydrogenated amino acids and resulted in good conversion and high enantioselectivity. This research opens the way for new ligand designs based on stereocontrol of supramolecular assemblies through stereodirecting chiral centers.     

Synthesis of axially chiral oxazoline–carbene coordinated palladium complexes with a N-phenyl framework

A family of tropos ligands bearing a N-heterocyclic carbene and a chiral oxazoline coordination group with a N-phenyl framework were easily prepared,and their coordination behavior with Pd(Ⅱ)acetate was performed,affording a series of axially chiral palladium complexes in good yields.     

Vicinal stereocontrol during nucleophilic addition to arene chromium tricarbonyl complexes: formal synthesis of (+/-)-erythro Juvabione

[reaction: see text] Vicinal stereocontrol during nucleophilic addition of tert-butyl lithiopropionate to eta(6)-anisole chromium tricarbonyl complexes with differing para substituents has been studied. Excellent vicinal double stereoinduction (>99:1) was observed when the para substituent was Si(CH(3))(3), and this has been applied to a stereoselective formal synthesis of (+/-)-erythro Juvabione. Asymmetric synthesis by chiral auxiliary directed nucleophilic addition is also discussed.