Chiral Chromium Research Articles

Asymmetric Propargylation of Benzaldehydes

The catalytic asymmetric Nozaki-Hiyama (NH) reaction provides direct access to useful chiral alcohols. Utilizing a novel chiral chromium catalyst, the authors report an efficient enantioselective propargylation of benzaldehyde derivatives, providing chiral homopropargyl alcohols with good yields and enantioselectivities.

ChemInform Abstract: Enantioselective Conjugate Addition of Diethylzinc to Chalcone Catalyzed by Chiral Tricarbonyl(arene)chromium/Nickel(II).

Abstract Enantioselective conjugate addition of diethylzinc to chalcone in the presence of Ni(acac)2 complexed with chiral tricarbonyl(1,2-disubstituted arene)chromium gave addition products with up to 78 % ee depending upon the amounts of Ni(II) and chiral arene chromium complexes.

Gold-catalyzed stereoselective reaction of tricarbonylchromium complexes of ortho-alkynyl benzaldehydes and benzaldimines with nucleophiles

Gold(I)-catalyzed reaction of ortho-alkynyl benzaldehyde tricarbonylchromium complexes with nucleophiles gave stereoselectively 1- anti- and syn-functionalized 1 H-isochromene chromium complexes depending on the nature of nucleophile. By reaction with alcohols, 1- anti-alkoxy 1 H-isochromene tricarbonylchromium complexes were obtained via gold benzopyrylium-type intermediates. On the other hand, carbon nucleophiles gave 1- syn-functionalized 1 H-isochromene chromium complexes via stereoselective addition of nucleophiles to the activated carbonyl group and following cyclization. Methoxy group of 1- anti-methoxy-1 H-isochromene chromium complex was substituted with carbon nucleophiles in the presence of Lewis acid to afford 1- anti-functionalized 1 H-isochromene chromium complexes. These methods can be applied to the synthesis of enantiomerically pure trans- and cis-1,3-dimethylisochromans starting from a single planar chiral chromium complex. Similarly, ortho-alkynyl benzaldimine tricarbonylchromium complexes gave stereoselectively 1- syn- and anti-functionalized dihydroisoquinoline chromium complexes by gold(I)-catalyzed reaction with nucleophile.

ChemInform Abstract: Catalytic Enantioselective Cycloadditions: A Readily Available Diels-Alder Catalyst.

Abstract A highly selective Diels–Alder catalyst has been prepared from a commercially available tetrahydronaphthalene diol. Stereocontrol is enhanced by introduction of a planar chiral arene chromium tricarbonyl group.

An Efficient Entry to Planar Chiral Organometallic Complexes via Pd-Catalyzed Asymmetric Hydrogenolysis

Planar chiral chromium- and ruthenium-based arene complexes were prepared with high levels of enantioselectivity via a Pd-catalyzed asymmetric hydrogenolysis reaction using a bulky chiral phosphoramidite ligand. Key elements for the efficiency of the process are the use of DABCO as borane-trapping reagent as well as substantial kinetic resolution, which was found to enhance the stereochemical outcome of the reaction.

Asymmetric Synthesis of Dienyl Alcohols

Addition reactions with allenyl metal reagents often suffer from regioselectivity issues and lead to isomeric mixtures. Although the reaction’s efficiency could be improved, the chiral chromium catalyst TBOxCrCl is unique in allowing to obtain single products in high enantioselectivity. Moreover, it avoids drawbacks associated with other methods (i.e., low regioselectivity, toxic reagents, lengthy starting material preparation).

Deeper Insight into the Mechanism of the Reaction of Photogenerated Metallaketenes and Imines

The reaction mechanism between Fischer carbene complexes and imines to produce beta-lactams has been studied by a combination of computational (DFT) and experimental methodologies. After the photogeneration of metalla-cyclopropanone species, the reaction initiates by 1,3-migration of the metal fragment from the former carbene carbon atom to the oxygen in the S o hypersurface. In spite of the endothermic nature of this rearrangement, it is biased by the more favorable HOMO(imine)-LUMO+1 interaction in the oxygen-coordinated ketene. This species reacts with the imine to yield metalla-zwitterions, which form the final products through a four electron conrotatory ring closure. The presence of the metal moiety during the whole reaction coordinate is demonstrated by the use of a chiral chromium(0) alkoxycarbene complex, which produces low but significant ee in the reaction with imines. The cis-trans stereoselection derives from the nucleophilic addition of the nitrogen atom of the imine to the oxygen-coordinated ketene, since there are no significant differences between the classical and the metallated processes in the electrocyclation step leading to the final 2-azetidinones.

Asymmetric, regio‐ and stereo‐selective alternating copolymerization of CO2 and propylene oxide catalyzed by chiral chromium Salan complexes

AbstractChiral chromium complexes of tetradentate N,N′‐disubstituted bis(aminophenoxide) (designated as Salan, a saturated version of Schiff‐base Salen ligand) in conjunction with an ionic quaternary ammonium salt can efficiently catalyze the copolymerization of CO2 with racemic propylene oxide (rac‐PO) at mild conditions to selectively afford completely alternating poly(propylene carbonate) (PPC) with ∼ 95% head‐to‐tail linkages and moderate enantioselectivity. These new catalyst systems predominantly exceed the previously much‐studied SalenCr(III) systems in catalytic activity, polymer enantioselectivity, and stereochemistry control. The chiral diamine backbone, sterically hindered substitute groups on the aromatic rings, and the presence of sp3‐hydridized amino donors and its N,N′‐disubstituted groups in chiral SalanCr(III) complexes all play significant roles in controlling polymer stereochemistry and enantioselectivity. Furthermore, a relationship between polycarbonate enantioselectivity and its head‐to‐tail linkages in relation to regioselective ring‐opening of the epoxide was also discussed on the basis of stereochemical studies of PPCs derived from the copolymerization of CO2 with chiral PO at various conditions. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 6102–6113, 2008

Asymmetric nitroaldol reaction catalyzed by a chromium(III)–salen system

Chiral chromium(III)–salen-type complexes derived from 1,2-diaminocyclohexane and 1,2-diphenylethylenediamine were found to catalyze the enantioselective Henry reaction. Various arylaldehydes, trans-cinnamaldehyde, and cyclohexanecarbaldehyde reacted with nitromethane in the presence of ( i-Pr) 2NEt and salen–CrCl (2 mol %) to give the corresponding adducts in 40–76% ee and in moderate to good yields.

Determination of the absolute configurations of chiral organometallic complexes via density functional theory calculations of their vibrational circular dichroism spectra: The chiral chromium tricarbonyl complex of N-pivaloyl-tetrahydroquinoline

The racemate of the chiral tricarbonyl-η 6-arene-chromium(0) complex, tricarbonyl-η 6- N-pivaloyl-tetrahydroquinoline-chromium(0), 1, has been synthesized and resolved using chromatography on a ( R, R)-Whelk-O1 column. The Absolute Configuration (AC) of 1 has been determined using vibrational circular dichroism (VCD) spectroscopy. The VCD spectrum of 1 has been predicted using the Stephens equation for vibrational rotational strengths, implemented using density functional theory (DFT) in the gaussian program. Using the B3PW91 functional and the 6-311++G (2d,2p) basis set, the predicted VCD spectrum of S- 1 is in excellent agreement with the experimental VCD spectrum of (+)- 1, leading unambiguously to the AC S-(+). It is concluded that VCD is a useful technique for determining the ACs of chiral organometallic complexes, given the use of optimum functionals and basis sets.

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.

Hydrolytic Kinetic Resolution of Epoxides Catalyzed by Chromium(III)‐endo,endo‐2,5‐diaminonorbornane‐salen [Cr(III)‐DIANANE‐salen] Complexes. Improved Activity, Low Catalyst Loading

AbstractThe hydrolytic kinetic resolution (HKR) of terminal epoxides, using chiral chromium(III)‐salen catalysts based on DIANANE (endo,endo‐2,5‐diaminonorbornane), was studied. A broad substrate scope was found for the chromium(III)‐DIANANE catalysts, and very low loadings (down to 0.05 mol %) were needed to achieve high enantiomeric purities of both the remaining epoxides and the product diols (up to >99 % ee). Besides monosubstituted epoxides, 2‐methyl‐2‐n‐pentyloxirane, which is an example for 2,2‐disubstituted epoxides, could be ring‐opened in an asymmetric fashion with water in the presence of an electronically tuned chromium(III)‐DIANANE complex.

Stereoselective Lewis Acid-Catalyzed α-Acylvinyl Additions

Silyloxyallenes derived from alpha-hydroxypropargylsilanes undergo efficient addition to aldehydes with catalytic amounts of Lewis acids. The allenes are accessed from the corresponding propargylsilanes in a base-catalyzed 1,2-Brook rearrangement/SE2' process. Enantioenriched propargylsilanes are synthesized by a new zinc-promoted addition of alkynes to acylsilanes in up to 74% ee. This work demonstrates that conversion to the silyloxyallenes occurs with minimal erosion in optical activity. The use of a chiral chromium(III) Lewis acid effects the catalytic asymmetric addition of racemic silyloxyallenes to aromatic aldehydes in up to 92% ee. The overall reaction is broad in scope and accommodates a wide variety of aromatic and aliphatic substituents on both the propargylsilane and aldehyde.

Chiral Chromium(III) Porphyrins as Highly Enantioselective Catalysts for Hetero‐Diels—Alder Reactions Between Aldehydes and Dienes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Catalytic asymmetric allylation of aldehydes using the chiral (salen)chromium(III) complexes

The enantioselective addition of allylstannanes to glyoxylates and glyoxals, as well as simple aromatic and aliphatic aldehydes, catalyzed by chiral (salen)Cr(III) complexes, has been studied. The reaction proceeded smoothly for the reactive 2-oxoaldehydes and allyltributyltin in the presence of small amounts (1–2 mol %) of (salen)Cr(III)BF 4 ( 1b) under mild, undemanding conditions. However, in the case of other simple aldehydes, the use of high-pressure conditions is required to obtain good yields. Classic chromium catalyst 1b, easily prepared from the commercially available chloride complex 1a, affords homoallylic alcohols usually in good yield and with enantiomeric purity of 50–79% ee. The stereochemical results are rationalized on the basis of the proposed model.

Chiral Chromium(III) Porphyrins as Highly Enantioselective Catalysts for Hetero‐Diels–Alder Reactions Between Aldehydes and Dienes

AbstractStarting from enantiomerically pure 5,10,15,20‐tetrakis[(1S,4R,5R,8S)‐1,2,3,4,5,6,7,8‐octahydro‐1,4 : 5,8‐dimethanoanthracene‐9‐yl]porphyrin, treatment with CrCl2 and subsequent air oxidation afforded the corresponding Cr(III) complex, with chloride as counterion, in 96% yield. Anion exchange with AgBF4 gave the corresponding tetrafluoroborate. These hitherto unknown chiral chromium porphyrins are efficient and highly enantioselective catalysts for the hetero‐Diels–Alder reaction of aliphatic, aromatic, and heteroaromatic aldehydes with dienes of varying electron density. In the case of 1‐methoxy‐3‐(trimethylsilyloxy)butadiene (“Danishefsky's diene”), enantiomeric excesses >90% were achieved in a number of cases, with furfural affording the highest ee (97%). Metal‐coordinating aldehydes such as pyridine‐2‐carbaldehyde do not inactivate the Cr(III) porphyrin catalyst. The cycloaddition of less electron‐rich dienes (such as 1‐methoxybutadiene) is effected as well, affording diastereoselectivities up to >99 : 1, and enantiomeric excesses >80%.

Enantiomeric Analysis of Planar Chiral (η6-Arene)chromium Tricarbonyl Complexes using NMR in Oriented Solvents

We investigate the analytical potential of proton-decoupled and proton-coupled carbon-13 NMR spectroscopy in chiral polypeptide liquid crystals for the enantiomeric discrimination of planar chiral (η6-arene)chromium tricarbonyl complexes. Experimental results obtained for chiral β-hydroxyamino alcohol and a series of chiral aldehydic complexes are reported and discussed in detail.

Asymmetric double ring-opening of a C2h-symmetric bis-epoxide: improved enantiomeric excess of the product through enantioselective desymmetrisation and ‘proof-reading’ steps

A new strategy in asymmetric synthesis is described in which the desymmetrisation of a C(2h)-symmetric molecule is followed by a subsequent enantioselective 'proof-reading' step. The double asymmetric ring-opening of the bis-epoxide (1R*,3R*,5S*,7S*)-4,8-dioxa-tricyclo[5.1.0.0(3,5)]octane with azidotrimethylsilane, catalysed by a chiral chromium Salen catalyst, was studied. The reaction involves the initial asymmetric ring-opening of the bis-epoxide to give the intermediate in moderate enantiomeric excess (ca. 50% ee); the second ring-opening step yields the required diazido diol, (1S,3S,4S,6S)-4,6-diazidocyclohexane-1,3-diol, in 72% yield and 70% ee. The origin of proof reading stems from the diversion of the minor enantiomer of the intermediate to a centrosymmetric by-product, a process which improves the enantiomeric excess of the required product. Using alternative conditions, the reaction was optimised to yield the required product in >98% ee.

Stereoselective [3,3]-Sigmatropic Rearrangement Promoted by the Metal [1,3]-Shift of Binuclear Fischer Carbene Complexes

Reaction of chiral homobinuclear Fischer chromium carbene complexes with allyl alcohol in the presence of NaH and the following oxidative demetalation gave alpha-allyl esters in up to 97% ee via [3,3]-sigmatropic rearrangement reaction promoted by the metal 1,3-shift. On the other hand, chiral heterobinuclear tungsten carbene complexes with arene chromium complexes afforded alpha-allyl-beta-hydroxy esters as a major product in up to 92/8 dr by the same reaction sequence.

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.