Chromium compounds reactions, enantioselectivity

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)... 

In a further development of the norbornene/anihne OHA reaction, Salzer and coworkers used planar chiral arene-chromium-tricarbonyl-based diphosphines for the in situ formation of cis-trans mixtures of complexes 9 and 10 that gave enanti-oselectivities of 51% and 70%, respectively, at 333 K and with a 40-fold excess of naked fluoride , but activities were very low. In the same paper complex 6 was shown to be superior in both activity and enantioselectivity (64% ee) to the corresponding Josiphos compound 5 [15]. The activated N-H bond of benzamide was also stereoselectively added across the double bond of norbornene to afford N-benzoyl-e%o-aminonorbornane in up to 50% yield and 73% ee in the presence of 0.5mol% [IrCl((R)-MeO-bipheb)]2 at 373 K [16]. 

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. 

The enantioselective lithiation of anisolechroimum tricarbonyl was used by Schmalz in a route towards the natural product (+)-ptilocaulin [88,89]. In situ hthiation of 125 with ent-83 gave enf-126 in an optimised 91% ee (reaction carried out at -100°C over 10 min). A second, substrate-directed lithiation with BuLi alone, formation of the copper derivative, and a quench with crotyl bromide, gave 135. The planar chirality and reactivity of the chromium complex was then exploited in a nucleophilic addition of dithiane, which generated the ptilocaulin precursor 136 (Scheme 35). The stereochemistry of compound 126 has also been used to direct dearomatising additions, yielding other classes of enones [90]. 

As with atropisomeric biaryls, axial chirality in atropisomeric amides maybe introduced by stereochemical control in the atroposelective reactions of planar chiral complexes [115]. Enantioselective lithiation was reported in this context by Uemura, who showed that the achiral complexes 195,198,201 and 204 are de-protonated enantioselectively by treatment with chiral lithium amide bases (Scheme 50) [116-118]. The stereogenic C-C and C-N axes in these compounds are orientated such that the larger NR2 and acyl groups, respectively, are directed away from the chromium. A range of chiral lithium amides was investigated, and by careful selection it was possible to obtain products 196,199,202 and 205... 

On an alternative pathway, internal Cannizzaro reactions afford mandelic acid-type compounds from phenylglyoxal derivatives [152-156]. Copper complexes [153, 154], chromium perchlorate [154], cobalt Schiff s bases [155] and yttrium chloride [156] have been applied as catalysts. An asymmetric version [Eq. (7)] has been developed using phenylglyoxal (14) as substrate and a combination of Cu(OTf)2 and (S,S)-Ph-box 16 as the chiral catalyst [154]. After 24 h at room temperature isopropyl man-delate (15) was obtained with an enantioselectivity of 28% ee. 

The same resolution can be efficiently carried out on structurally more complex compounds that are optically active for the helical structure of the molecule, i.e., bis(hydroxymethyl) thiaetherohelicene [160]. In this way, a nearly optically pure helical molecule can be obtained (Scheme 33). This method has been successfully applied also to resolution of organometallic compounds and a few interesting results are shown in Scheme 34. Tiicarbonyl [(ir (6)-cycloheptatriene)chromium(0)] and ferrocenyl alcohols have been examined as substrates of the lipase-catalyzed acylation, and the reaction can be accomplished in a highly enantioselective manner [161,162]. 

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