Chromium-arene complexes diastereoselective

Dotz has reviewed the use of chiral centers in either the alkyne or chromium carbene to control the facial selectivity of the chromium arene complex. Examples of these diastereoselective benzannulations exist with the controlling stereocenter in the alkyne, the chromate ester (or amide), or the unsaturated carbene. ... 

The chromium-templated coupling of alkenyl- or arylcarbene, aUcyne and carbonyl ligands generates arene tricarbonylchromium complexes as primary benzannulation products which - based on their unsymmetric substitution pattern - bear a plane of chirality. Chiral arene complexes are powerful reagents in stereoselective synthesis however, the preparation of pure enantiomers is a lengthy and often tedious procedure, and thus diastereoselective benzannulation appears to be an attractive alternative. In order to lure the chromium fragment to one or the other face of the arene formed, chiral information may be incorporated in the carbene complex or the aUcyne. 

This chapter will be divided into two distinct parts. Firstly, general methods for making Ti -arene chromium tricarbonyl complexes will be discussed. Particular attention will be paid to complexes bearing sulfinyl substituents and protocols for their synthesis will be given. The second part will deal with enantiopure or enriched complexes. Examples of diastereoselective syntheses of optically pure 1,2-disubstituted complexes with amino and hydroxyl groups at the two benzylic positions will be presented. 

Let s now look at a recent approach to the problem. It is actually a study wherein the problem was used to learn something about the stereochemical course of a new reaction. The Pearson group was studying reactions of ester enolates with arene chromium tricarbonyl complexes. As part of this study, the reaction of anisole derivatives (85) with the enolate derived from terf-butyl propionate was examined. The result was formation of a chromium tricarbonyl complex of a l-methoxy-l,3-cyclohexadiene of type 86. Conversion of the chromium-diene complex into a cyclohexenone would provide material that could serve as an intermediate in a juvabione syntheses if the reaction took place with good diastereoselectivity. 

A 1,2 or 1,3 unsymmetrically disubstituted arene is prochi-ral and therefore the corresponding chromium tricarbonyl compounds are chiral. (Substituted arene) complexes with amine, carboxyl, and formyl groups at the ortho position are resolved into optically active chromium complexes through corresponding diastereomeric adducts (eq 25). Biocatalysts also perform the kinetic resolution of racemic chromium complexes (eq 26). The optically active chromium complexes can be prepared by di-astereoselective ortho lithiation of the chiral benzaldehyde or acetophenone acetal complexes, and diastereoselective chromium complexation of the chiral ort/io-substituted benzaldehyde am-inals (eq 27). Catalytic asymmetric cross-coupling of meso (1,2-haloarene)chromium complex produces chiral monosubstituted complexes. The chiral (arene)chromium complexes can be used as ligands in asymmetric reactions. ... 

Due to the inherent unsymmetric arene substitution pattern the benzannulation reaction creates a plane of chirality in the resulting tricarbonyl chromium complex, and - under achiral conditions - produces a racemic mixture of arene Cr(CO)3 complexes. Since the resolution of planar chiral arene chromium complexes can be rather tedious, diastereoselective benzannulation approaches towards optically pure planar chiral products appear highly attractive. This strategy requires the incorporation of chiral information into the starting materials which may be based on one of three options a stereogenic element can be introduced in the alkyne side chain, in the carbene carbon side chain or - most general and most attractive - in the heteroatom carbene side chain (Scheme 20). 

The same chiral auxiliary has also been used for the stereoselective synthesis of arene-chromium complexes treatment of an aromatic aminal with chromium hexacarbonyl gives the corresponding complex with high diastereomeric excess. This protocol was recently applied in a total synthesis of (—)-lasubine (eq 4). A successful application of 1,2-diaminocyclohexane (as its IR,2R enantiomer) as a chiral auxiliary is illustrated by the di-astereoselective alkylation of the potassium enolate of bis-amide (3) with electrophiles such as benzyl bromide to give bis-alkylated products with excellent diastereoselectivity (eq 5). Lower levels... 

Alkyllithium addition to the (ti -arene) dicarbonylchromium imine chelates has been examined. Treatment of optically pure chelate (41) with methyllithium provides amine (42) with an enantiomeric excess of 94% (Scheme 5). No diastereoselectivity was reported for alkyllithium additions to (arene)tri-carbonylchromium complex (40). In the absence of additional examples, the generality of this chromium chelate methodology for asymmetric amine synthesis cannot be assessed. 

Similarly, chromium-complexed benzylic cations are also stabilized and organic reactions based on the benzylic cation species have been developed. For example, planar chiral o-substituted benzaldehyde dimethylacetal chromium complexes 4 were treated with 3-buten-l-ol in the presence of TiCl4 to give tet-rahydropyran derivatives with high diastereoselectivity (Eq. 5) [5]. The chromium-complexed benzylic oxonium ion 6 would be also generated and subsequent intramolecular cyclization afforded the cyclization product 7. Furthermore, the chromium-complexed benzyl alcohol derivative having electron-rich arene ring at the side chain produced tetrahydroisoquinoline skeleton by treatment with Lewis acid with stereochemical retention at the benzylic position (Eq. 6) [6]. 

Similarly, the planar chiral tricarbonylchromium complexes of ortho substituted benzaldimines are useful for a variety of stereoselective cycloaddition reactions. For example, the benzaldimine chromium complexes gave aza-Diels-Alder product, 2,3-dihydro-4-pyridinone chromium complexes with high diastereoselectivity by reaction with Danishefsky s diene (Eq. 18) [11,17,18]. The high diastereoselectivity of the cycloadducts is also based on the preferred antz-conformation of the starting benzaldimine chromium complexes as well as the planar chiral benzaldehyde chromium complexes. The cycloaddition of imines having arene chromium complex at the remote position with Danishefsky s diene underwent smoothly in good yields, but the diastereoselectivity was low (Eq. 19) [17]. 

Similarly, ketene generated from acid chloride by treatment with triethyl-amine reacted with tricarbonylchromium-complexed benzaldimines to afford P-lactam derivatives via [2+2] cycloaddition with high diastereoselectivity. Thus, the cycloaddition of benzaldimine chromium complexes with ketenes generated from acid chloride at 0 °C in the presence of triethylamine afforded czs-p-lactam as a single diastereomer 27 (Eq. 20) [19]. Remote positioned imine having the planar chiral arene chromium complex was also reacted with ketene to afford p-lactam complex as diastereomeric mixture (Eq. 21) [19]. 

An intramolecular cycloaddition of aza-diene 41 with arene chromium complex in the presence of Lewis acid afforded the chromium-complexed tetrahyd-roquinoline derivatives in good yields with high diastereoselectivity (Eq. 29)... 

Diels-Alder reaction with cyclopentadiene gave the corresponding adduct (Eq. 31) [28]. (Dihydronaphthalene)chromium complex gave addition product by reaction with diazomethane with high diastereoselectivity [29]. The acrylate having chiral arene chromium complex underwent Diels-Alder reaction with high selectivity in the presence of Lewis acid (Eq. 32) [30]. 

One of the first eye-catching synthetic applications of arene-chromium chemistry was the synthesis of the sp/ro-sesquiterpenes ( )-acorenone and ( )-acorenone B (rac-7) disclosed by Semmelhack and Yamashita in 1980 [14]. These authors twice exploited the meta-selective nucleophile addition to anisole-Cr(CO)3 derivatives (Scheme 1). Starting from complex rac-1, such a reaction is first used for the regioselective introduction of an acyl sidechain to give 2 after oxidative workup. A few steps later, the nitrile rac-4 (obtained from rac-3 by complexation and separation of the diastereomeric products by preparative HPLC) is deprotonated to form the spiro addition product rac-5, from which the enone rac-6 is obtained after protonation and hydrolysis of the initially formed dienol ether. The final conversion of rac-6 into acorenone B (rac-7) efficiently proceeds over five steps and involves a diastereoselective hydrogenation of an exo-methylene group. 

The synthesis of planar-chiral arene chromium complexes has been reviewed several times and has also been discussed in an earlier article [9,10]. Apart from stereoselective complexation reactions, diastereoselective and enantioselective... 

As a consequence of the unsymmetric substitution pattern encountered in the arene ring (OH versus OR) formed upon benzannulation the chromium complexes bear a plane of chirality. Complexes of this type are powerful reagents in stereoselective synthesis, and approaches directed towards diastereoselective benzannulation will be addressed in section 2.1 of this review. 

The chromium complex 46 of benzaldehyde imine is also a good substrate for asymmetric conjugate addition of organolithium reagents, where the reaction was mediated by a stoichiometric amount of chiral diether 18 in toluene to give, following propargylic electrophile incorporation, the cyclohexadienal 48 in up to 93% ee (Scheme 13) [38]. SAMP [(S)-l-amino-2-(methoxymethyl)pyrrolid-ine] hydrazones were used effectively in diastereoselective nucleophilic additions to (arene)Cr(CO)3 complexes [39]. 

Planar chiral compounds usually (and for the purpose of this review, always) contain unsymmetrically substituted aromatic systems. Chirality arises because the otherwise enantiotopic faces of the aromatic ring are differentiated by the coordination to a metal atom - commonly iron (in the ferrocenes) or chromium (in the arenechromium tricarbonyl complexes). Withdrawal of electrons by the metal centre means that arene-metal complexes and metallocenes are more readily lithiated than their parent aromatic systems, and the stereochemical features associated with the planar chirality allow lithiation to be diastereoselective (if the starting material is chiral) or enantioselective (if only the product is chiral). 

The use of chiral tricarbonyl (Ti -arene) chromium complexes in the highly stereoselective synthesis is well demonstrated. Baldoli et al. have amply demonstrated the application of this strategy in the synthesis of titled compounds. Known chiral ortfto-substituted benzaldehyde tricarbonyl chromium complexes were exposed to lithium acetylide in THE to furnish diastereoselective adducts in good yields (Scheme 21.9). 

Miscellaneous Reactions. In addition to the key reactions above, DDQ has been used for the oxidative removal of chromium, iron, and manganese from their complexes with arenes and for the oxidative formation of imidazoles and thiadia-zoles from acyclic precursors. Catal)ftic amounts of DDQ also offer a mild method for the oxidative regeneration of carbonyl compounds from acetals, which contrasts with their formation from diazo compounds on treatment with DDQ and methanol in nonpolar solvents. DDQ also provides effective catalysis for the tetrahydropyranylation of alcohols. Furthermore, the oxidation of chiral esters or amides of arylacetic acid by DDQ in acetic acid provides a mild procedure for the synthesis of chiral a-acetoxy derivatives, although the diastereoselectivity achieved so far is only 65-67%. ... 

If an ortho- or meia-disubstituted benzene derivative with a stereogenic centre on one of the side chains is used, complexation may occur with significant diastereoselectivity. This results from delivery of the chromium tricarbonyl group to one of the diastereotopic faces of the arene unit it is, in general, facilitated by lower temperature conditions for the complexation step. A spectacular example is represented in Scheme 6.2. ... 

Chiral starting materials offer a diastereoselective version producing enantio-enriched planar chiral benzannulation products. Chiral arene chromium complexes are attractive reagents for stereoselective synthesis but the conventional methods to obtain them in optically pure form are tedious [27]. The chiral information can be introduced in the alkyne side chain as demonstrated for bulky a-chiral propargylic ethers 13 that result in very high diastereoselectivities for the annulation of chromium alkenylcarbene 12 (Scheme 11.7) [28]. 

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