Rhodium enantiomerically pure

A new chiral auxiliary based on a camphor-derived 8-lactol has been developed for the stereoselective alkylation of glycine enolate in order to give enantiomerically pure a-amino acid derivatives. As a key step for the synthesis of this useful auxiliary has served the rc-selective hydroformylation of a homoallylic alcohol employing the rhodium(I)/XANTPHOS catalyst (Scheme 11) [56]. 

An alternative approach to hydroboration has utilized a chiral B-H source with either achiral or chiral rhodium complexes.58 The enantiomerically pure reagent (21) is derived from ephedrine. Notably in the reactions with BINAP, a higher enantiomeric excess is produced from (R)-BINAP (6) compared to the Y-form (Scheme 13). 

Enantiomerically pure 2-alkylidenetetrahydrofurans were prepared by TiCl4 mediated reactions of 1,3-bis-silyl enol ethers with enantiomerically pure epichlorohydrin <06TA892>. Rhodium complexes as the one shown below reacted in solution in the presence of triethylphosphine to afford 2,2-disubstituted-5-methylenetetrahydrofurans in good yield <06JA9642>. 

Optically active aldehydes are important precursors for biologically active compounds, and much effort has been applied to their asymmetric synthesis. Asymmetric hydroformylation has attracted much attention as a potential route to enantiomerically pure aldehyde because this method starts from inexpensive olefins and synthesis gas (CO/H2). Although rhodium-catalyzed hydrogenation has been one of the most important applications of homogeneous catalysis in industry, rhodium-mediated hydroformylation has also been extensively studied as a route to aldehydes. 

Another interesting issue is the possibility of creating optically active compounds with racemic catalysts. The term chiral poisoning has been coined for the situation where a chiral substance deactivates one enantiomer of a racemic catalyst. Enantiomerically pure (R,R)-chiraphos rhodium complex affords the (iS )-methylsuccinate in more than 98% ee when applied in the asymmetric hydrogenation of a substrate itaconate.109 An economical and convenient method... 

Enantiomerically pure copper and rhodium complexes enable enantioselective catalysis of carbene-mediated reactions. Such reactions will be discussed more thoroughly in Section 4.2. Experimental Procedure 4.1.1 describes the preparation of an enantiomerically pure rhodium(II) complex which has proven efficient for catalysis of different types of carbene complex-mediated C-C-bond-forming reactions with high asymmetric induction. 

Enantiomerically pure rhodium(II) complexes have been shown to catalyze enantioselective, intramolecular C-H insertions. Because high enantioselectivities (> 97% ee [1092]) can be achieved, it can be inferred that in the transition state of these C-H insertions the catalyst is in close proximity to the reacting groups. With the same type of catalyst highly enantioselective (up to 93% ee) intermolecular C-H insertions can also be realized [1093]. 

Intramolecular carbene C-H insertion frequently leads to the formation of five-membered rings [967,990,1021,1113-1128], In particular l-diazo-2-alkanones tend to yield cyclopentanones exclusively when treated with rhodium(ll) carboxylates. The use of enantiomerically pure catalysts for diazodecomposition enables the preparation of non-racemic cyclopentane derivatives [1005,1052,1074,1092,1129]. Intramolecular 1,5-C-H insertion can efficiently compete with 1,2-C-H insertion... 

Few examples of preparatively useful intermolecular C-H insertions of electrophilic carbene complexes have been reported. Because of the high reactivity of complexes capable of inserting into C-H bonds, the intermolecular reaction is limited to simple substrates (Table 4.9). From the results reported to date it seems that cycloalkanes and electron-rich heteroaromatics are suitable substrates for intermolecular alkylation by carbene complexes [1165]. The examples in Table 4.9 show that intermolecular C-H insertion enables highly convergent syntheses. Elaborate structures can be constructed in a single step from readily available starting materials. Enantioselective, intermolecular C-H insertions with simple cycloalkenes can be realized with up to 93% ee by use of enantiomerically pure rhodium(II) carboxylates [1093]. 

For intermolecular cyclopropanations with unsubstituted diazoacetates the highest asymmetric inductions can be achieved with the copper(I) complexes of C2-symmetric, bidentate ligands developed by Pfaltz (e.g. 1) and Evans (2). The chiral rhodium(II) complexes known today do not generally lead to such high enantiomeric excesses as copper complexes in intermolecular cyclopropanations. For intramolecular cyclopropanations, however, chiral rhodium(II) complexes are usually superior to enantiomerically pure copper complexes [1374]. 

In particular the synthetic approach to dihydrofurans (first equation in Figure 4.23) represents a useful alternative to other syntheses of these valuable intermediates, and has been used for the preparation of substituted pyrroles [1417], aflatoxin derivatives [1418], and other natural products [1419]. The reaction of vinylcarbene complexes with dienes can lead to the formation of cycloheptadienes by a formal [3 + 4] cycloaddition [1367] (Entries 9-12, Table 4.25). High asymmetric induction (up to 98% ee [1420]) can be attained using enantiomerically pure rhodium(II) carboxylates as catalysts. This observation suggests the reaction to proceed via divinylcyclopropanes, which undergo (concerted) Cope rearrangement to yield cycloheptadienes. 

The kinetic resolution was systematically studied by using diastereomerically pure en-ynes and an enantiomerically pure rhodium(I) catalyst (Scheme 8.9). Each product was obtained in high yield ( 100% for the reacted 51-i-unreacted 50) and high enantiomeric purity. Furthermore, these results were validated by subjecting each enantiomer... 

All approaches to the design of enantiomerically pure rhodium(II) catalysts had depended on the attachment of enantiomerically pure ligands to the rhodium core. In collaboration with Professor Pascual Lahuerta of the University of Valencia, Spain, we undertook a complementary strategy, the preparation of rhodium(I I)-dimers (P)-56 and its enantiomer (M)-56, having backbone chirality [23]. Using the approach outlined above, we calculated that the transition state 52 should be favored over the transition state 53 by 4.2 kcal moU. ... 

For the synthesis of optically pure building blocks we mainly focused on the synthesis of protected noncoded (R)- and (S)-amino acids, as they can be synthesized reliably in enantiomerically pure form with a large variety of side chains using asymmetric hydrogenation of a-amino-a, 3-didehydroamino acids using cationic diphosphine rhodium catalysts.216,217 As a typical example of a reactophore we present a-alkynyl ketones, which is a representative bis-acceptor molecule. In Scheme 5 are depicted some of the many synthetic applications of acetylenic ketones in heterocyclic synthesis, which have great potential for combinatorial and parallel organic synthesis. 

The decahydroisoquinoline derivative NVP-ACQ090 (124) is a potent and selective antagonist at the somatostatin sst3 receptor. The asymmetric hydrogenation of allylic alcohol 125 with a rhodium catalyst that contained (S)-TMBTP produced (A )-126 (97.5% ee) (Scheme 12.50). The authors indicated that enantiomerically pure 124 could be obtained from material acquired by asymmetric hydrogenation and that the process is suitable for large-scale production.156... 

Evans et al. have recently demonstrated a highly enantioselective synthesis of allyl amines 52 from enantiomerically pure carbonates 51 catalyzed by rhodium complexes (Eq. (13)) [33], The reaction proceeds with excellent regioselectivities, and the allyl amines are isolated in high yields and with a high degree of conservation of the optical purity. The scope of this reaction is demonstrated by the synthesis of, e.g., optically active nitrogen-containing heterocycles. 

This possibility of intimate association of rhodium with the aromatic ring suggests further experiments. A logical extension of asymmetric syntheses involving prochir-al reactants is a kinetic resolution with related chiral reactants under similar conditions. In the one case of hydroboration-amination where this has been applied, it has proved to be very effective. The reactant was prepared directly by a Heck reaction on 1,2-dihydronaphthalene, and under the standard conditions of catalytic hydrobora-tion gave >45% of both enantiomerically pure recovered alkene with (after oxidative work-up) the alcohol of opposite hand, mainly as the trans-isomer. This procedure forms a simple and potentially useful route to pharmacologically active substances, demonstrated by the racemic synthesis shown [105] (Scheme 34). 

In recent years the synthesis of chiral and achiral tripodal phosphines and their application in homogeneous catalysis has been studied in more detail [2]. Enantiomerically pure tripodal ligands were synthesized from the corresponding trichloro compounds and chiral, cyclic lithio-phosphanes, e.g. 17, (Scheme 6) [21,22], Using a rhodium(I) complex of ligand 18, an enantiomeric excess of 89 % was obtained in the asymmetric hydrogenation reaction of methyl acetami-docinnamate (19). 

In asymmetric catalysis a prochiral substrate binds to an enantiomerically pure catalyst to generate a pair of diastereomeric intermediates. The energy difference and the rate of exchange between them controls the optical yield (e.e.) of the final product. In the case of a-aminocinnamic acid derivatives, the acyl auxiliary on the nitrogen is required to enable the substrate to form a chelate complex with rhodium.12 The mechanism of this reaction is shown in Fig. 22-3 the ligand in this case is DIPAMP (22-XV). 

This collection begins with a series of three procedures illustrating important new methods for preparation of enantiomerically pure substances via asymmetric catalysis. The preparation of 3-[(1S)-1,2-DIHYDROXYETHYL]-1,5-DIHYDRO-3H-2.4-BENZODIOXEPINE describes, in detail, the use of dihydroquinidine 9-0-(9 -phenanthryl) ether as a chiral ligand in the asymmetric dihydroxylation reaction which is broadly applicable for the preparation of chiral dlols from monosubstituted olefins. The product, an acetal of (S)-glyceralcfehyde, is itself a potentially valuable synthetic intermediate. The assembly of a chiral rhodium catalyst from methyl 2-pyrrolidone 5(R)-carboxylate and its use in the intramolecular asymmetric cyclopropanation of an allyl diazoacetate is illustrated in the preparation of (1R.5S)-()-6,6-DIMETHYL-3-OXABICYCLO[3.1. OJHEXAN-2-ONE. Another important general method for asymmetric synthesis involves the desymmetrization of bifunctional meso compounds as is described for the enantioselective enzymatic hydrolysis of cis-3,5-diacetoxycyclopentene to (1R,4S)-(+)-4-HYDROXY-2-CYCLOPENTENYL ACETATE. This intermediate is especially valuable as a precursor of both antipodes (4R) (+)- and (4S)-(-)-tert-BUTYLDIMETHYLSILOXY-2-CYCLOPENTEN-1-ONE, important intermediates in the synthesis of enantiomerically pure prostanoid derivatives and other classes of natural substances, whose preparation is detailed in accompanying procedures. 

Intermediate enolates derived from Michael-type processes can be isolated. For example, enantiomerically pure enolate (5 )-131 can be isolated, as is the case of the almost enantiomerically pure enolate (5 )-131, prepared by 1,4-addition of the phenyl-substituted borane 130 to enone 129, in the presence of a substoichiometric amount of the chiral rhodium mediator [Rh(OMe)(COD)]2-(5 )-BINAP (COD = 1,5-cyclooctadiene, equation 33). Protonation of (5 )-131 with methanol leads to cyclohexanone (5 )-132 in good yield with no loss of enantiomeric purity (equation 34). The protonation is presumably diastereoselective, taking place on the less hindered face of (5)-131, away from the neighbouring phenyl group, as can be inferred from the stereochemical outcome (133)... 

Rhodium-Catalyzed Asymmetric Hydrogenation of Olefins. MiniPHOS (1) can be used in rhodium-catalyzed asymmetric hydrogenation of olefinic compounds. The complexation with rhodium is carried out by treatment of 1 with [Rh(nbd)2]BF4in THF (eq 2). The hydrogenation of a-(acylamino)acrylic derivatives proceeds at room temperature and an initial H2 pressure of 1 or 6 atm in the presence of the 0.2 mol% MiniPHOS-Rh complex 2. The reactions are complete within 24—48 h to afford almost enantiomerically pure a-amino acids (eq 3). Itaconic acids, enamides, and dehydro-3-ami no acids can also be hydrogenated with excellent enantioselectivity (eq 4—6). 

Enantiomerically pure carboxylic acids are routinely obtained from N-acylsultams by Hydrogen Peroxide assisted saponification with Lithium Hydroxide in aqueous THF. 4 Alternatively, transesterification can be effected under neutral conditions in allyl alcohol containing Titanium Tetraisopropoxide, giving the corresponding allyl esters which can be isomerized/hydrolyzed with Wilkinson s catalyst (Chlorotris(triphenylphosphine)rhodium(I)) in Et0H-H20. This provides a convenient route to carboxylic acids containing base-sensitive functionality. Primary alcohols are obtained by treatment with L-Selectride (Lithium Tri-s-butylborohydride) in THF at ambient temperature. ... 

An enantiomerically pure aldehyde, (lR,2R,3R)-2,7,7-trimethylbicyclo[3.1.1]hep-tane-2-aldehyde, is produced from a-pinene by rhodium-catalyzed hydroformylation [79, 80]. Initially, reaction with ferrocene under acidic conditions leads to a 1 1 mixture of diastereoisomeric cations, but on standing for a few hours at room temperature, isomerization by rotation around the ferrocene — cationic carbon bond to the thermodynamically more stable cation (with configuration (R) at the cationic center) occurs (Fig. 4-11). An enantiomerically pure amine is available by trapping of this cation by azide and reduction [75]. Analogously, the isomeric aldehyde with the bicyclo [2.2.1] heptane structure is formed by hydroformylation of a-pinene with cobalt catalysts [79, 80] and was used as the starting material for an isomeric series of chiral amines [75]. 

---