Enantioselective synthesis chromium complexes

The potential of Fischer carbene complexes in the construction of complex structures from simple starting materials is nicely reflected in the next example. Thus, the reaction of alkenylcarbene complexes of chromium and tungsten with cyclopentanone and cyclohexanone enamines allows the di-astereo- and enantioselective synthesis of functionalised bicyclo[3.2.1]octane and bicyclo[3.3.1]nonane derivatives [12] (Scheme 44). The mechanism of this transformation is initiated by a 1,4-addition of the C -enamine to the alkenylcarbene complex. Further 1,2-addition of the of the newly formed enamine to the carbene carbon leads to a metalate intermediate which can... 

An enantioselective approach to cytotoxic nor-calamenenes via electron-transfer-driven benzylic umpolung of an arene tricarbonyl chromium complex. Synthesis 2003, 1851-1855. 

Another landmark development in the area of hDA chemistry is the emergence of the tridentate chromium complexes 194 that can catalyze the reaction of njl-unsaturatcd aldehydes with vinyl ethers to afford dihydropyrans with high diastereo- and enantioselectivity (Equation 91) <2002AGE3059>. The same catalytic system can be used for the asymmetric synthesis of the 3,4-dihydropyran 195 from 3-boronoacrolein pinacolate and ethyl vinyl ether in quantitative yield (Equation 92) <2003JA9308, 2005JA1628>. 

The benzannulation affords arene-Cr(CO)3 complexes possessing a plane of chirality resulting from the unsymmetrical arene substitution pattern. This aspect is relevant to stereoselective synthesis, in which enantiopure arene tricarbonyl chromium complexes play a major role [56]. The benzannulation reaction avoids both harsh conditions incompatible with the retention of chiral information and the cumbersome separation of enantiomers, and is thus attractive for the diastereo- and enantioselective synthesis of arene complexes [17b, 57]. 

The third approach to obtain diarylmethylpiperazine derivatives uses the highly stereospecific chiral oxazaborolidine-catalyzed reduction, using catecholborane as the reductant of the 4-bromobenzophenone chromium tricarbonyl complex, as described by Corey and Helal [59], followed by the stereospecific displacement of the hydroxyl benzyl group by the /V-substituted-piperazine [44]. As outlined in Scheme 2, Delorme et al. [44] used this approach for the enantioselective synthesis of compound 31, (+)-4-[ (aS)-a-(4-benzyl-l-piperazinyl)benzyl]-lV,lV-diethylben-zamide. Lithiation of the readily available benzene chromium tricarbonyl with n-BuLi in the presence of TMEDA in THF at —78 °C, followed by addition of... 

Keywords Arene chromium complexes Arene ruthenium complexes Enantioselective total synthesis Planar-chiral metal complexes Natm-al products... 

As a consequence, arene-Cr(CO)3 complexes offer new and unique opportunities for the stereoselective multi-step synthesis of complex molecules. By focusing on applications in the enantioselective total synthesis of natural products (and relevant analogs), this review intends to highlight the state of the art of synthetic arene chromium chemistry. It will be shown that highly original and competitive overall syntheses can be achieved especially in those cases, where the whole strategy is based on arene chromium chemistry and the chemical and stereochemical effects of the Cr(CO)3 unit can be exploited in several subse-... 

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... 

Another applieation of photogenerated metal coordinated ketenes is based on the addition of protie nucleophiles and has been exploited in the synthesis of amino aeids and peptides. [66] As usual, the reactive intermediate is generated by photolysis of an aminoearbene complex 46, which may be a-alkylated in a previous step. The oxazolidine auxiliary applied successfully inducing asymmetry in the P-laetam formation, allowed an enantioselective synthesis of amino aeids. Sinee both enantiomers of the auxiliary may be obtained from the corresponding phenyl glycine enantiomer, natural (5) and non-natural R) amino acid esters 47 are accessible via this route (Scheme 25). A recent review on synthetical applications of chromium carbene photochemistry has been published, [li]... 

Considering the unique features that the Nozaki-Hiyama-Kishi reaction possesses and its undoubted potential in the synthesis of complex natural products, the development of an efficient enantioselective version to control the absolute stereochemical outcome for a range of processes was highly desirable. However, because of the difficulties such as ligand coordination and specificity combined with the tendency of chromium(II) to form dimers or clusters with polydentate ligands, considerable effort has been devoted to the development of enantioselective variants. These studies have resulted in the expansion of the NHK to now include an impressive array of carbon-carbon, bond-forming processes (Scheme 12.6). 

This is all very well but what about using dienes which are more typically electron rich (with one oxygen substituent instead of two) 255 in combination with normal aliphatic aldehydes 256 A catalyst that could achieve this would be very useful. One solution is a modification of the chromium salen complex which replaces half the salen with an adamantyl group and the other half with d.v-aminoindanol 209. The synthesis of this complex 258 is straightforward since commercially available compounds 257 and 209 are combined in high-yielding reactions and the complex itself is impressively enantioselective.58 The hexafluoroantimonate catalyst 260 was more enantioselective than the corresponding chloride 259. 

Umani-Ronchi adapted the Furstner protocol to achieve the first catalytic, enantioselective variant of this reaction. The chiral chromium salen complex was prepared from the in situ reduction of the anhydrous CrCb to CrCl2 with an excess of manganese metal, followed by complexation with the salen ligand 8 in the presence of catalytic triethylamine." Then the addition of allylic chloride (9) to aldehydes 10 to give the allylic alcohols 11 in moderate yields and in up to 95% ee. The same groups employed the same conditions for the addition of 2-butenyl bromides to aldehydes to achieve up to 83 17 syn/anti of allylic alcohol products and for the addition of 1,3-dichloropropene to aromatic aldehydes to obtain the syn chlorohydrin adduct in modest yield which were further converted to optically active vinyl epoxides. The [Cr(salen)]-catalyzed addition of propargyl halides to aromatic aldehydes allowed the synthesis of enantiomerically enriched homopropargyl alcohols in moderate yields with up to 56% ee. ... 

A more significant growth on enantioselective hetero Diels-Alder reactions has been pioneered by the Jacobsen group [44-46], The HD A reactions of less nucleophilic dienes than Danishefsky s diene were successfully realized by employing Jacobsen s chiral tridentate Schifif base chromium(lll) complex 1.42 [46-48], This powerfiil method has been utilized on multiple occasions in total synthesis. For example, Patterson and coworkers applied this concept to a synthesis of leucascandrolide A [49], Aliphatic aldehyde 1.40 coupled with diene 1.41 using Jacobsen s chromium catalyst furnished the 2,6-cw-tetrahydropyranone 1.43 with high stereoselectivity (Scheme 1,7),... 

The base-catalysed hydrophosphonylation of aldehydes or imines (Pudovik reaction) [58] as a convenient method was widely used for the synthesis of 1-hydrox-yalkylphosphonates. Since the pioneering work of Shibuya [50] and Spilling [51] was reported, much attention has been devoted to developing enantioselective catalysts for the synthesis of chiral 1 -hydroxy alkylphosphonates. Chiral aluminium complexes were shown to be more effective chiral catalysts [59-62]. Based on the success of using A1 (salen) and A1 (salcyen) as asymmetric catalysts, Al-Schiff base complexes [63, 64] have been developed to catalyze the asymmetric addition reaction of dial-kylphosphonates and aldehydes. Tridentate Schiff base metal complexes, such as vanadium, chromium, and iron [65], have been successfully applied in many asymmetric synthetic reactions. We noticed that Al(III) complexes could catalyse the asymmetric Pudovik reaction and these ligands could be easily synthesized [66-70]. 

In the 15 years since Fiirstner et al. developed the first NHK reaction using catalytic quantities of chromium, the subsequent stereoselective, catalytic variant has become a valuable tool in catalytic asymmetric synthesis. Many studies on the NHK reaction have focused on the application of ligands that have proven successful in a range of other catalytic asymmetric processes. For example, the salen- and oxazoline-derived ligands that have been applied have advanced the scope of the NHK reaction in terms of reactivity and asymmetric induction in a wide array of carbon-carbon forming processes. These processes now include allylation, crotylation, vinylation, methallylation, aUenylation, homoallenylation, and propargylation. Xia and Yamamoto s TBOxCr(III)Cl complex has afforded some of the highest levels of enantioselectivity in a series of allylation, crotylation, aUenylation, and more recent dienylation and alkynylation studies. 

Jacobsen reported that chiral chromium(III) complexes prepared from tri-dentate Schiff base ligands, such as 254, are catalysts for enantioselective cycloadditions of aldehydes and electron-rich dienes (Scheme 17.36) [126]. The synthetic potential of this powerful method was exploited in the elegant total synthesis of the antifungal agent ambrucitin (259) [127]. The synthesis sequence included the use of asymmetric hetero-Diels-Alder reactions to... 

Apart from aminolysis and olefin metathesis the photoactivation of aminocar-bene complexes offers another nonconventional entry into peptide synthesis. Irradiation into the hypsochromic MLCT-band of chromium aminocarbenes such as 201 generates a ketene-like intermediate 204 that is trapped by amino acid esters such as 202 or 205 to produce dipeptides 203 or 206 after enantioselective protonation (Scheme 11.49) [106]. This photochemical protocol generally combines good yields with high diastereoselectivities and is especially attractive for the incorporation of a-alkyl a-amino acid esters into peptides that may be hampered in conventional peptide synthesis methodologies due to steric hindrance [106c]. 

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