Systems asymmetric variant

An asymmetric variant of this reaction was developed using chiral Pd complex 111 with either silanes or disiloxanes [66-68]. Both relative and absolute stereochemistries were controlled in this system and good yields (60-85%) were obtained after oxidation (Eq. 18). Formation of the silane-containing product was inhibited by the presence of water due to competitive formation of the palladium hydrides and silanols [68]. The use of disiloxanes as reductants, however, provided expedient oxidation to the alcohol products without decreasing the isolated yields enantioselectivity was 5-15% lower in this more robust system [66]. Benzhydryldimethylsilane proved to be a good compromise between high yield and facile oxidation [66]. Palladium com-... 

A very simple yet elegant method for efficient epoxidation of aromatic and aliphatic alkenes was presented by Beller and coworkers [63, 64], FeCl3 hexahydrate in combination with 2,6-pyridinedicarboxylic add and various organic amines gave a highly reactive and selective catalyst system. An asymmetric variant (for epoxidations of trans-stilbene and related aromatic alkenes) was published recently [65] using N-monosulfonylated diamines as chiral ligands (Scheme 3.7). 

The first reports on iron-catalyzed aziridinations date back to 1984, when Mansuy et al. reported that iron and manganese porphyrin catalysts were able to transfer a nitrene moiety on to alkenes [90]. They used iminoiodinanes PhIN=R (R = tosyl) as the nitrene source. However, yields remained low (up to 55% for styrene aziridination). It was suggested that the active intermediate formed during the reaction was an Fev=NTs complex and that this complex would transfer the NTs moiety to the alkene [91-93]. However, the catalytic performance was hampered by the rapid iron-catalyzed decomposition of PhI=NTs into iodobenzene and sulfonamide. Other reports on aziridination reactions with iron porphyrins or corroles and nitrene sources such as bromamine-T or chloramine-T have been published [94], An asymmetric variant was presented by Marchon and coworkers [95]. Biomimetic systems such as those mentioned above will be dealt with elsewhere. 

A Pd-catalyzed oxidative cyclization of phenols with oxygen as stoichiometric oxidant in the noncoordinating solvent toluene has been developed for the synthesis of dihydrobenzo[ ]furans (Equation 136). Asymmetric variants of this Wacker-type cyclization have been reported by Hayashi and co-workers employing cationic palladium/2,2 -bis(oxazolin-2-yl)-l,l -binaphthyl (boxax) complexes <1998JOC5071>. Stoltz and co-workers have reported ee s of up to 90% when (—)-sparteine is used as a chiral base instead of pyridine <2003AGE2892, 2005JA17778>. Attempts to effect such a heteroatom cyclization with primary alcohols as substrates, on the other hand, led to product mixtures contaminated with aldehydes and alkene isomers, which is in contrast to the reactions with the Pd(ii)/02 system in DMSO <1995TL7749>. 

Recently, the asymmetric variants of the Stetter [114-118], crossed-benzoin [114, 117-120], and transeslerification [121] reactions have attracted great interest as asymmetric nucleophilic acylation processes. A prerequisite for asynunetric catalysis is the availability of a chiral catalyst. Introduction of chirahty into the thiamin framewoik follows the same principles as that for the related imidazoUum systems, mainly the introduction of a chiral centre next to the nitrogen atom of the thiazole ring [117]. 

In 1999, Cozzi and Umani-Ronchi described a diastereoselective intermolecular pinacol coupling of aromatic and aliphatic aldehydes in the presence of a catalytic quantity of TiCl4(THF)2/Schiff base (Eq. 3.38) [60]. Manganese is employed as the stoichiometric reductant with the Cozzi/Umani-Ronchi system, zinc generally affords a lower yield of the diol. The reaction is believed to proceed via a pathway analogous to that illustrated in Fig. 3-5. The observations of Cozzi and Umani-Ronchi that the Schiff base affects reaction diastereoselectivity and increases the reaction rate bode well for studies of asymmetric variants. In an initial investigation, these workers obtained 10% ee in a reductive dimerization of benzaldehyde (Eq. 3.39). 

There has been significant interest in the development of a catalytic asymmetric Pauson-Khand type reaction because of its vast potential in organic synthesis. A boom in research activity in this field has focused in two areas - the development of catalytic Pauson-Khand type cyclizations and of stoichiometric syntheses of optically active cyclopentenones via the Pauson-Khand reaction, including a recent report of the first intramolecular catalytic asymmetric Pauson-Khand type cyclization. In this review, the existing catalytic systems will be briefly surveyed followed by a detailed analysis of the asymmetric variant. The stoichiometric syntheses of optically active cyclopentenones will also be discussed. 

Another important development in the area of catalytic Pauson-Khand type cy-clizations has been the discovery of other transition metal carbonyl complexes which are capable of effecting the catalytic synthesis of cyclopentenones. Two recent reports from Murai and Mitsudo detailed a Ru3(CO)i2-catalyzed enyne cyclocarbonylation, Eqs. (10) and (11) [34,35]. While this protocol allowed for the cyclization of a variety of l,6-enynes,the cyclizations of terminal alkynes as well as 1,7-enynes were problematic. The feasibility of using Cp2Ti(CO)2 as a catalyst for the intramolecular Pauson-Khand type cyclization of a variety of 1,6-and 1,7-enynes (vide infra) has also been demonstrated [36]. Based on the wide array of transition metals that are capable of effecting stoichiometric Pauson-Khand type cyclizations (vide supra), the development of more catalytic systems is to be expected this should greatly facilitate the search for catalytic asymmetric variants. 

The nitroaldol (Henry) reaction involves the addition of nitronates to aldehydes and ketones to give a P-nitroalcohol. These products are usefrd synthetic building blocks as the nitro group can be transformed into a range of other functional groups, and this has stimulated some recent research into the development of a catalytic asymmetric variant. Some of the catalyst systems used in the asymmetric aldol rection have been successfully employed in the catalytic asymmetric nitroaldol process. 

More recently, Beller and coworkers have shown that the ruthenium complex 6 (Fig. 7.9) is an effective epoxidation catalyst, for a variety of olefins, with 3 equiv. of 30% H2O2 at very low catalyst loadings (0.005 mol%). A tertiary alcohol such as fert-amyl alcohol was used as a cosolvent. Based on its high activity and broad scope this system appears to have considerable synthetic potential, which may be adapted to afford effective asymmetric variants in the future. Indeed, a truly effective catalyst, with broad scope, for asymmetric epoxidation with aqueous hydrogen peroxide, preferably in the absence of organic solvents, is still an important and elusive goal in oxidation chemistry. 

In 1977, Trost published the first example of an asymmetric variant of the Tsuji-Trost reaction, termed the asymmetric allylic alkylation reaction (AAA). Much of the subsequent development of the AAA reaction can be attributed to the dedicated work of Trost and co-workers.There was a substantial time lag however, in the development of processes where high enantioselectivities were realized in a predictable fashion. This was due, in part, to the fact that chiral, asymmetrically pure ligands must create a chiral environment on the opposite face of the allyl fragment to the metal centre (a stereoelectronic requirement, vide infra)P This obviously represents a significant design challenge in the production of effective ligand systems. 

An asymmetric variant of this reaction can be carried out introducing a camphor-derived 1-azabutadiene ligand. Enantiomeric excess values of up to 86% can be achieved with this system to obtain planar chiral iron complexes. The photolytically induced reaction of pentacarbonyliron with prochiral cyclohexa-1,3-dienes can also be run enantioselectively using a chiral 1-azabutadiene catalyst. Quantitative yields and ee values up to 86% are possible under these conditions. Cyclic 1,4-dienes can also be complexed by pentacarbonyliron under concomitant rearrangement to the 1,3-diene... 

Axial Chirality. For a system with four groups arranged out of the plane in pairs about an axis, the system is asymmetric when the groups on each side of the axis are different. Such a system is referred to as an axial chiral system. This structure can be considered a variant of central chirality. Some axial chiral molecules are allenes, alkylidene cyclohexanes, spiranes, and biaryls (along with their respective isomorphs). For example, compound 7a (binaphthol), which belongs to the class of biaryl-type axial chiral compounds, is extensively used in asymmetric synthesis. Examples of axial chiral compounds are given in Figure 1-5. 

Zhou and Hartwig recently discovered the beneficial effect of added potassium hexamethyldisilazanide (KHMDS) base for the asymmetric addition of aniUnes to norbornenes, thereby widening the synthetic scope of the original CMM system (see Table 6.2) [17]. [IrCl(COE)2]2 and two equivalents of variants of the Segphos and Biphep Ugands first presumably form complexes 8, 11, and 12 in situ (see Chart 1) and then in combination with co-catalytic KHMDS generate the catalytically active species (see Table 6.2 and Section 6.4 for a discussion of the mechanism). 

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