Chiral chromium

Chiral salen chromium and cobalt complexes have been shown by Jacobsen et al. to catalyze an enantioselective cycloaddition reaction of carbonyl compounds with dienes [22]. The cycloaddition reaction of different aldehydes 1 containing aromatic, aliphatic, and conjugated substituents with Danishefsky s diene 2a catalyzed by the chiral salen-chromium(III) complexes 14a,b proceeds in up to 98% yield and with moderate to high ee (Scheme 4.14). It was found that the presence of oven-dried powdered 4 A molecular sieves led to increased yield and enantioselectivity. The lowest ee (62% ee, catalyst 14b) was obtained for hexanal and the highest (93% ee, catalyst 14a) was obtained for cyclohexyl aldehyde. The mechanism of the cycloaddition reaction was investigated in terms of a traditional cycloaddition, or formation of the cycloaddition product via a Mukaiyama aldol-reaction path. In the presence of the chiral salen-chromium(III) catalyst system NMR spectroscopy of the crude reaction mixture of the reaction of benzaldehyde with Danishefsky s diene revealed the exclusive presence of the cycloaddition-pathway product. The Mukaiyama aldol condensation product was prepared independently and subjected to the conditions of the chiral salen-chromium(III)-catalyzed reactions. No detectable cycloaddition product could be observed. These results point towards a [2-i-4]-cydoaddition mechanism. 

Jacobsen et al. took an important step towards the development of a more general catalytic enantioselective cycloaddition reaction of carbonyl compounds by introducing chiral tridentate Schiff base chromium(III) complexes 15 (Scheme 4.15)... 

The major developments of catalytic enantioselective cycloaddition reactions of carbonyl compounds with conjugated dienes have been presented. A variety of chiral catalysts is available for the different types of carbonyl compound. For unactivated aldehydes chiral catalysts such as BINOL-aluminum(III), BINOL-tita-nium(IV), acyloxylborane(III), and tridentate Schiff base chromium(III) complexes can catalyze highly diastereo- and enantioselective cycloaddition reactions. The mechanism of these reactions can be a stepwise pathway via a Mukaiyama aldol intermediate or a concerted mechanism. For a-dicarbonyl compounds, which can coordinate to the chiral catalyst in a bidentate fashion, the chiral BOX-copper(II)... 

A chiral nonracemic cyclic allyl iodide was shown to react with excess chromium(II) chloride and (4-methoxyphenylmethoxy)acetaldehyde to yield a single diastereomer, which was converted to la,25-dihydroxy vitamin D332. 

The stereoselectivities of reactions when both components are chiral, were also studied12. In matched pairs and, as well, in several mismatched combinations very high selcctivities of the same sense are observed. This indicates that the stereodirecting influence of the chromium reagents usually dominates (Table 3). 

In a rather different approach optically active chromium complexes of 2,3-dihydro-1 H-in-denone are used as chiral enolate precursors. These chiral complexes react with 3-buten-2-one in benzene using l,5-diazabicyclo[4.3.0]non-5-ene as the base. The diastereomeric ratio of the product is the same irrespectively of whether the exo- or the Noisomer of the chromium... 

Asymmetric versions of the cyclopropanation reaction of electron-deficient olefins using chirally modified Fischer carbene complexes, prepared by exchange of CO ligands with chiral bisphosphites [21a] or phosphines [21b], have been tested. However, the asymmetric inductions are rather modest [21a] or not quantified (only the observation that the cyclopropane is optically active is reported) [21b]. Much better facial selectivities are reached in the cyclopropanation of enantiopure alkenyl oxazolines with aryl- or alkyl-substituted alkoxy-carbene complexes of chromium [22] (Scheme 5). 

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). 

A similar tandem Dotz-Mitsunobu reaction has been reported starting from a l,6-methano[10]annulene carbene complex, but no conclusion could be reached on the influence of the chiral information regarding the stereoselective course of the reaction since the chromium fragment could not be kept coordinated to the benzannulation product [47]. 

The inherent plane of chirality in the metal carbene-modified cyclophane 45 was also tested in the benzannulation reaction as a source for stereoselectivity [48]. The racemic pentacarbonyl(4-[2.2]metacyclophanyl(methoxy)carbene)-chromium 45 reacts with 3,3-dimethyl-1-butyne to give a single diastereomer of naphthalenophane complex 46 in 50% yield the sterically less demanding 3-hexyne affords a 2 1 mixture of two diastereomers (Scheme 30). These moderate diastereomeric ratios indicate that [2.2]metacyclophanes do not serve as efficient chiral tools in the benzannulation reaction. 

Table 3 Reaction of chromium alkoxycarbenes with chiral heterocyclic imines ...

Photodriven reactions of Fischer carbenes with alcohols produces esters, the expected product from nucleophilic addition to ketenes. Hydroxycarbene complexes, generated in situ by protonation of the corresponding ate complex, produced a-hydroxyesters in modest yield (Table 15) [103]. Ketals,presumably formed by thermal decomposition of the carbenes, were major by-products. The discovery that amides were readily converted to aminocarbene complexes [104] resulted in an efficient approach to a-amino acids by photodriven reaction of these aminocarbenes with alcohols (Table 16) [105,106]. a-Alkylation of the (methyl)(dibenzylamino)carbene complex followed by photolysis produced a range of racemic alanine derivatives (Eq. 26). With chiral oxazolidine carbene complexes optically active amino acid derivatives were available (Eq. 27). Since both enantiomers of the optically active chromium aminocarbene are equally available, both the natural S and unnatural R amino acid derivatives are equally... 

The intramolecular cyclization route to p-lactams still provides interest. P-Amino esters (obtained by a Reformatsky-type reaction of an imine and bromoacetates derived from chiral alcohols) are cyclized by the action Grignard reagents to 4-substituted P-lactams with impressive e.e. <96TL4095>. A similar approach through a Reformatsky-type reaction uses tricarbonyl(Ti -benzaldimine)chromium complexes and ultrasound <96T4849>. 3-Methyl-azetidin-2-ones (obtained from 3-amino-2-methylpropionates) have been resolved and their... 

Recently, Lacour, Sauvage and coworkers were able to show that the association of chiral [CuL2] complexes (L=2-R-phen,6-R-bpy and2-iminopyridine) with TRISPHAT 8 leads to an NMR enantiodifferentiation, which allows the determination of the kinetics of racemization of the complexes (bpy=2,2 -bipyri-dine phen=l,10-phenanthroline) [119]. This type of application has recently been reported in conjunction with chiral sandwich-shaped trinuclear silver(l) complexes [122]. Several reports, independent from Lacour s group,have confirmed the efficiency of these chiral shift agents [123-127]. Finally, TRISPHAT can be used to determine the enantiomeric purity of (r] -arene)chromium complexes. These results broaden the field of application of 8 to chiral neutral, and not just cationic, species [114,128,129]. 

Mulzer J, Ohler E (2004) Olefin Metathesis in Natural Product Syntheses. 13 269-366 Muniz K (2004) Planar Chiral Arene Chromium (0) Complexes as Ligands for Asymetric Catalysis. 7 205-223 Murai S, see Kakiuchi F (1999) 3 47-79... 

The chiral bimetallic complex 1653 reacts with TMSOTf 20 in the presence of excess styrene, via 1654, to give the cyclopropane complex 1655 in high yield [38]. The chromium can be readily removed from 1655 by treatment with I2 in Et20. Analogously, the complex 1656 reacts with styrene in 90% yield, via 1657, to give MegSiOH 4 and phenylcyclopropane 1658 [39] (Scheme 10.17). 

The chiral diol 17 derived from tartaric acid is exploited in the titanium-catalyzed asymmetric pinacol coupling in the presence of Zn and MesSiCl to give the corresponding diol in 11-71 ee % [44], The chiral salen ligands 18-20 are used in the titanium-catalyzed enantioselective coupling reaction, which achieves the higher selectivity [45-47]. The chromium complex with TBOxH (21) efficiently catalyzes the asymmetric coupling reaction of both aromatic and aliphatic aldehydes [48]. 

A short review of heterobond cleavage and sequential reactions of 1,2-thiazetidinones (P-sultams) has appeared <99PS193>. The first data for optically active P-sultams 33 have been reported. The precursor of 33 was the sulfonamide 32 which was obtained by use of a chiral tricarbonyl(r 6-arene)chromium(0) complex <99T14089>. 

Chromium carbene complexes have also been known to react with imine equivalents to afford /3-lactam derivatives234. Furthermore, [3 + 2]-cycloaddition of an alkenylchromium carbene 133 with imines proceeded to afford 3-pyrroline derivatives 134 in the presence of a Lewis acid catalyst (Equation (21)),235 where GaClj or Sn(OTf)2 were efficient promoters. Alkenylcarbenes bearing chiral auxiliaries afforded the desired cycloadduct in optically pure form. 

Two methods have been developed to provide enantiomerically enriched cycloadducts using the chromium-mediated [6 + 2]- and [6 + 4]-cycloadditions one involving a chiral resolution and the other involving the attachment of a chiral auxiliary to the triene. The lipase resolution method provides access to either enantiomer of the chromium complex, albeit with moderate enantiomeric excesses (Scheme 34).119 The [6 + 4]- and [6 + 2]-reactions of chiral substrates such as 116 which are available by the attachment of a removable chiral auxiliary (R ) to the triene moiety are highly diastereoselective (Equation (17)).120... 

Although disubstituted alkynes are used successfully as two-carbon components in chromium-mediated and -catalyzed [6 + 2]-reactions, the use of terminal alkynes produces a [6 + 2 + 2]-reaction (Section 10.13.3.7). Buono and co-workers have discovered that when a cobalt catalyst is employed, several monosubstituted alkynes can be used in [6 + 2]-cycloadditions with cycloheptatriene (Scheme 35). The use of a chiral BINOL-phosphoramidite cobalt complex affords an enantioselective [6 + 2]-cycloaddition reaction (Equation (18)).121... 

Salzer et al. prepared a set of planar-chiral diphosphine ligands based on the arene chromium tricarbonyl backbone (Fig. 36.3) [21]. The straightforward four-step synthetic route allowed the preparation of 20 ligands of this family. These ligands were tested in Ru- and Rh-catalyzed enantioselective hydrogenation of various substrates, including the standard C=C substrates (dimethyl itaconate, methyl-2-acetamidocinnamate, methyl-2-acetamidoacrylate) as well as MEA-imine (l-(methoxymethyl)ethylidene-methylethylaniline) and ethyl pyruvate. Moderate conversions and ee-values were obtained. 

Schaus et al.41 have also reported an asymmetric hetero Diels-Alder reaction of Danishefsky s diene 10042 with aldehyde 101 catalyzed by chromium(III) complex 99 bearing a similar chiral salen ligand. Product 102 is obtained in moderate to good yield and stereoselectivity (Scheme 5-31 and Table 5-5). 

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