Racemate kinetic, Jacobsen

One way of overcoming these problems is by kinetic resolution of racemic epoxides. Jacobsen has been very successful in applying chiral Co-salen catalysts, such as 21, in the kinetic resolution of terminal epoxides (Scheme 9.18) [83]. One enantiomer of the epoxide is converted into the corresponding diol, whereas the other enantiomer can be recovered intact, usually with excellent ee. The strategy works for a variety of epoxides, including vinylepoxides. The major limitation of this strategy is that the maximum theoretical yield is 50%. 

Jacobsen has utilized [(salen)Co]-catalyzed kinetic resolutions of tenninal epoxides to prepare N-nosyl aziridines with high levels of enantioselectivity [72], A range of racemic aryl and aliphatic epoxides are thus converted into aziridines in a four-step process, by sequential treatment with water (0.55 equivalents), Ns-NH-BOC, TFA, Ms20, and carbonate (Scheme 4.49). Despite the apparently lengthy procedure, overall yields of the product aziridines are excellent and only one chromatographic purification is required in the entire sequence. 

Two recent reports described addition of nitrogen-centered nucleophiles in usefully protected fonn. Jacobsen reported that N-Boc-protected sulfonamides undergo poorly selective (salen) Co-catalyzed addition to racemic epoxides. However, by performing a one-pot, indirect kinetic resolution with water first (HKR, vide infra, Table 7.1) and then sulfonamide, it was possible to obtain highly enantiomer-ically enriched addition products (Scheme 7.39) [71]. These products were transformed into enantioenriched terminal aziridines in straightforward manner. 

The hydrolytic kinetic resolution (HKR) of terminal epoxides using Co-salen catalysts provides a convenient route to the synthesis of enantioemiched chiral compounds by selectively converting one enantiomer of the racemic mixture (with a maximum 50% yield and 100% ee) (1-3). The use of water as the nucleophile makes this reaction straightforward to perform at a relatively low cost. The homogeneous Co(III) salen catalyst developed by Jacobsen s group has been shown to provide high... 

In the realm of hydrolytic reactions, Jacobsen has applied his work with chiral salen complexes to advantage for the kinetic resolution of racemic epoxides. For example, the cobalt salen catalyst 59 gave the chiral bromohydrin 61 in excellent ee (>99%) and good yield (74%) from the racemic bromo-epoxide 60. The higher than 50% yield, unusual for a kinetic resolution, is attributed to a bromide-induced dynamic equilibrium with the dibromo alcohol 62, which allows for conversion of unused substrate into the active enantiomer <99JA6086>. Even the recalcitrant 2,2-disubstituted epoxides e.g., 64) succumbed to smooth kinetic resolution upon treatment with... 

Jacobsen s cobalt and chromium salen complexes 69 and 70 have proven extremely successful in the enantioselective ring opening of meso-epoxides (and kinetic resolution of racemic epoxides). Recent accounts of these most efficient and practical catalysts can be found elsewhere [71-73]. 

Much activity continues to be centered around the preparation of enantioenriched epoxides using chiral Co(III)-, Mn(III)- and Cr(III)-salen complexes, particularly in the area of innovative methods. A recent brief review <02CC919> focuses on the synthesis, structural features, and catalytic applications of Cr(III)-salen complexes. In an illustrative example, Jacobsen and coworkers <02JA1307> have applied a highly efficient hydrolytic kinetic resolution to a variety of terminal epoxides using the commercially available chiral salen-Co(III) complex 1. For example, treatment of racemic m-chlorostyrene oxide (2) with 0.8 mol% of catalyst 1 in the presence of water (0.55 equiv) led to the recovery of practically enantiopure (> 99% ee) material in 40% yield (maximum theoretical yield = 50%). This method appears to be effective for a variety of terminal epoxides, and the catalyst suffered no loss of activity after six cycles. 

A so far still unsolved problem is the direct enantioselective epoxidation of simple terminal olefins. For example the epoxidation of propylene that was achieved with a 41% ee almost twenty years ago by Strukul and his coworkers using Pt/diphosphine complexes is still unsurpassed. Unfortunately such low ee s are of no practical interest. The problem was circumvented by Jacobsen using hydrolytic kinetic resolution of racemic epoxides (Equation 26) and is practised on a multi 100 kg scale at Chirex. The strategy used is to stereose-lectively open the oxirane ring of a racemic chiral epoxide leaving the other enantiomer intact. Reactions are carried out to a 50% maximum conversion. The catalyst belongs to the metal-salen class described above and can be recycled. The products are separated by fractional distillation. 

Kinetic resolution in the catalytic conversion of racemic chloro propanols to optically active epoxides has been achieved by use of a chiral Co(salen) type complex in combination with K2CO3. Although enantioselectivity was modest (< 35 % ee), this first use in asymmetric epoxide formation of the chiral ligand system that was later brought to fame through the Jacobsen-Katsuki asymmetric epoxidation is noteworthy [56,57]. When applied to the prochiral l,3-dichloro-2-propanol, asymmetric induction of up to ca. 60 % ee was achieved (Sch. 8) [58]. 

A synthetic strategy based on Jacobsen s hydrolytic kinetic resolution of readily available racemic epoxide 345 offers the possibility to produce in a good yield enantiomerically enriched (R,R) and (A,A)-epoxides 345 as chiral building blocks for the preparation of (R)-lipoic acid and (A)-lipoic acid (Scheme 66) <200681863>. 

The hydrolytic kinetic resolution (HKR) of racemic epoxides using Jacobsen s chiral Co(III)(salen)-OAc complex 36a as a catalyst is one of the most practical approaches to the preparation of enantiopure terminal epoxides (Scheme 7.15) [47, 53]. Although the chiral catalyst is readily accessible and displays high enantioselectivity, it provides only relatively low turnover numbers. Thus, in order to facilitate catalyst separation and reuse, several attempts were made to anchor Jacobsen s catalyst onto insoluble supports [54]. Although these heterogeneous... 

Industrialization studies of the Jacobsen hydrolytic kinetic resolution of racemic epichlorhy-drin... 

Larrow and Jacobsen have reported that the kinetic resolution of racemic in-dene oxide with Mn-salen complex 3 proceeds with a moderate level of relative rate constant (ks/kj.=6.5) (Scheme 4) [12]. 

Chiral Catalysts Containing Group 7 Metals (Mn, Tc, and Re). Most of the chiral manganese complexes belong to the Mn(III)-salen-type complexes (Fig. 17), which are effective catalysts in asymmetric epoxidation (147). (The most widely used one is the Jacobsen s catalyst, iV,Ar -bis(3,5-di-terf-butylsalicylidene)-l,2-cyclohexanediamino-manganese(III) chloride.) These types of catalysts are also efficient for enantioselective aziridination (148), kinetic resolution of racemic allene via enantiomer differentiating oxidation (149), and enantiotopic selective... 

In 2004, Umani-Ronchi et al. discovered that chiral (RJi)-[Cr(salen)]Y complexes (Jacobsen catalysts 70/71) could effectively undergo asymmetric F-C alkylation via kinetic resolution of racemic disubstituted epoxides. Treatment of 2-methylindole 74 with 3 equiv trans-1,2-disubstituted epoxides (72a-d) and 3.5 mol % of (/ ,/ )-[Cr(salen)]SbF6 catalyst (71) provided excellent yields (82-99%) of the corresponding chiral P-indolyl alcohols (73a-d) with good optical purity (72-91% ee). With this catalyst, only the (5 iS)-isomer of 72a-d reacts to form the (J ,S)-isomer of 73a-d, respectively. 

Alcohol 143 (Scheme 6.26), prepared from (R)-glyceraldehyde derivative, was subjected to deoxygenation and epoxidation to give the racemic epoxide 144. Kinetic resolution with (S,S)-Jacobsen catalyst gave diol 145, which on further transformations was converted into the alcohol 146. Swern oxidation of 146 followed by Wittig olefination, acetonide deprotection under acidic conditions furnished the diol 147. Primary alcohol on deoxygenation through LAH reduction of tosylate afforded the alcohol 148. 

The Salen motif has been widely utilized as a ligand for transition metals. Jacobsen et al. reported that chiral salen-cobalt complex (Co-salen) could be utilized as a Lewis acid catalyst for hydrolytic kinetic optical resolution of racemic... 

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