Asymmetric rearrangement, enantioselective

B. Enantioselective Access to Allylic Alcohols via Asymmetric Rearrangement... 

As with many catalytic systems, additives can play an important role. During optimization of the asymmetric rearrangement of cyclopentenyl tertiary ethers to chiral cyclohexenyl tertiary ethers, Hoveyda found a strong solvent effect on the enantioselectivity of the reaction using (97b). Lewis basic (see Lewis Acids Bases) additives were used to modify the catalyst since (97i) is Lewis acidic and coordination could change the equilibration of the Mo-alkyhdene isomers and, thus, could alter the enantioselectivity. Coordination of Lewis base to the metal center might also change the fit of the chiral pocket. Addition of 10 equiv (vs. substrate) of THF substantially increased the enantiomeric excess of the product in the model transformation (Table 10). ft was surmised that... 

The use of Al(III) complexes as catalysts in Lewis acid mediated reactions has been known for years. However, recent years have witnessed interesting developments in this area with the use of ingeiuously designed neutral tri-coordinate Al(lll) chelates. Representative examples involving such chelates as catalysts include (1) asymmetric acyl halide-aldehyde cyclocondensations, " (2) asymmetric Meerwein-Schmidt-Ponndorf-Verley reduction of prochiral ketones, (3) aldol transfer reactions and (4) asymmetric rearrangement of a-amino aldehydes to access optically active a-hydroxy ketones. It is important to point out that, in most cases, the use of a chelating ligand appears critical for effective catalytic activity and enantioselectivity. 

Isomerization of allylic alcohols occurs in reasonable yields but with poor enantioselectivity [22], although kinetic resolution of 4-hydroxycyclopentenone has been reported [23]. Reliable laboratory-scale procedures for the synthesis of BINAP and for the asymmetric rearrangement have been published [24,25], making this a good candidate for further applications in asymmetric synthesis. 

A recent example has been described by Brown et al. who have studied the KR of p-nitrophenyl esters of the d- and i-N-tert-butoxycarbonyl derivatives of glutamine and phenylalanine with ethanol or methanol promoted by chiral lanthanide complexes, providing enantioselectivities of up to 99% ee [302]. On the other hand, an enantioselective hydrolysis of phenylalanine derivatives was reported in 1986, providing a perfect enantiomer discrimination (s> 1000), as a result of catalysis with a tripeptide [303]. In 2007, Maruoka et al. reported the KR of differently a,a-disubstituted a-siloxy aldehydes based on an asymmetric rearrangement into the corresponding chiral acyloins using axially chiral organoaluminium Lewis acids, which provided selectivity factors of up to 39.5... 

The Rh2(DOSP)4 catalysts (6b) of Davies have proven to be remarkably effective for highly enantioselective cydopropanation reactions of aryl- and vinyl-diazoacetates [2]. The discovery that enantiocontrol could be enhanced when reactions were performed in pentane [35] added advantages that could be attributed to the solvent-directed orientation of chiral attachments of the ligand carboxylates [59]. In addition to the synthesis of (+)-sertraline (1) [6], the uses of this methodology have been extended to the construction of cyclopropane amino acids (Eq. 3) [35], the synthesis of tricyclic systems such as 22 (Eq. 4) [60], and, as an example of tandem cyclopropanation-Cope rearrangement, an efficient asymmetric synthesis of epi-tremulane 23 (Eq. 5) [61]. 

The premier example of this process in an ylide transformation designed for [2,3]-sigmatropic rearrangement is reported in Eq. 15 [107]. The threo product 47 is dominant with the use of the chiral Rh2(MEOX)4 catalysts but is the minor product with Rh2(OAc)4. That this process occurs through the metal-stabilized ylide rather than a chiral free ylide was shown from asymmetric induction using allyl iodide and ethyl diazoacetate [107]. Somewhat lower enantioselectivities have been observed in other systems [108]. 

In 1997 the first asymmetric aza-Claisen rearrangement was reported by Overman et al. [55], which made use of diamines as bidentate ligands for Pd(II), allowing for moderate enantioselectivities. In the same year, Hollis and Overman described the application of the planar chiral ferrocenyl palladacycle 38 as a catalyst for the enantioselective aza-Claisen rearrangement of benzimidates 39 (Fig. 19) [56]. A related ferrocenyl imine palladacycle provided slightly inferior results, while a benzylamine palladacycle lacking the element of planar chirality was not able to provide any enantioselectivity [57]. 

A method for highly efficient asymmetric cyclopropanation with control of both relative and absolute stereochemistry uses vinyldiazomethanes and inexpensive a-hydroxy esters as chiral auxiliaries263. This method was also applied for stereoselective preparation of dihydroazulenes. A further improvement of this approach involves an enantioselective construction of seven-membered carbocycles (540) by incorporating an initial asymmetric cyclopropanation step into the tandem cyclopropanation-Cope rearrangement process using rhodium(II)-(5 )-N-[p-(tert-butyl)phenylsulfonyl]prolinate [RhjtS — TBSP)4] 539 as a chiral catalyst (equation 212)264. 

High levels of asymmetric induction can be achieved intramolecularly if the substrate functionality and the heteroatom ligand are contained in the same molecule. Chiral amido(a]kyl)cuprates derived from allylic carbamates [(RCH= CHCH20C(0)NR )CuR undergo intramolecular allylic rearrangements with excellent enantioselectivities (R = Me, n-Bu, Ph 82-95% ee) [216]. Similarly, chiral alkoxy(alkyl)cuprates (R OCuRLi) derived from enoates prepared from the unsaturated acids and trans-l,2-cyclohexanediol undergo intramolecular conjugate additions with excellent diasteroselectivities (90% ds) [217]. 

In the past few years, new approaches for the enantioselective synthesis of / -benzyl-y-butyrolactones appeared in the literature. Some of these approaches involve the asymmetric hydrogenation of 2-benzyl-2-butenediols (j [34]), the radical mediated rearrangement of chiral cyclopropanes (r [35]), the transition metal catalyzed asymmetric Bayer-Villiger oxidation of cyclobutanones n [36]), or the enzymatic resolution of racemic succinates (g [37]). 

In contrast to the asymmetric activation of C—H bonds in benzyl silyl ethers, the dirhodium tetraprolinate, Rh2(5-DOSP)2 (Figure 5.7), was found to be an efficient catalyst in an enantioselective C—H activation of acetals (Scheme 5.16). Interestingly, when the acetals had a methoxy substituent on the aromatic ring, the Stevens rearrangement was a main competing side reaction of the C—H activation of acetals. 

In a related process, Johnson and co-workers have developed an asymmetric metallophosphite-catalyzed intermolecular Stetter-hke reaction employing acyl silanes [81, 82], Acyl silanes are effective aldehyde surrogates which are capable of forming an acyl anion equivalent after a [l,2]-Brook rearrangement. The authors have taken advantage of this concept to induce the catalytic enantioselective synthesis of 1,4-dicarbonyls 118 in 89-97% ee and good chemical yields for a,p-unsaturated amides (Table 11). Enantioselectivities may be enhanced by recrystallization. 

Recently, a more versatile enantioselective variant was accomplished by use of the chiral bis(oxazoline) 27 as a chiral coordinating agent . For example, a rearrangement of dibenzyl ether 25 using the premixed complex t-BuLi (2.0 equivalents)/(5, 5 )-27 (1.0 equivalents) in ether at —78 °C afforded 94% yield of alcohol (S)-26 in 62% ee. Furthermore, an asymmetric catalytic version of this rearrangement has been developed (equation 14). This protocol provides the tertiary alcohol 29 with a relatively high % ee from rac-28 (equation 15). 

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