Esters enantioselective synthesis from

The levels of selectivity achieved in these reactions are amongst the highest reported for non-enzymatic acylative KR, and the scope of the method has been reviewed by Vedejs [40], as has its application in PKR [43]. The PBO catalysts 2a-c are prepared by a multi-step enantioselective synthesis from lactate esters [42, 44] and are air-sensitive hence, the reactions are generally run in de-oxygenated solvents. However, the air-stable tetrafluoroboric acid salts of these catalysts can also be employed with in-situ deprotonation by EtsN these conditions give results comparable with those obtained using the original protocol [45]. (For experimental details see Chapter 14.17.1). 

Hydroxyalkylphosphonates have been prepared by reduction of the corresponding ketones. These include phosphonomalate esters by highly diastereose-lective reduction of 3-phosphonopyruvates with NHs.BHa and both 2-hydroxyalkyl-phosphonates, e.g. 178, and thiophosphonates by asymmetric hydrogenation using chiral ruthenium catalysts. An enantioselective synthesis, from 179, of both enantiomers of phosphonothrixin 180 and their absolute stereochemistry have been reported.The epoxide 179 was prepared from 2-methy -3-hydroxymethyl-1,3-butadiene via a Sharpless epoxidation. 

A [2 + 2] photoaddition-cycloreversion was applied to the enantioselective synthesis of the natural product byssocMamic add (Figure 6.11). Desymmetrization of a meso-cyclopentene dimethyl ester with PLE in pH 7 buffer-acetone (5 1) provided a monoacid, one of the photopartners. It is noteworthy that both enantiomers of this natural product were synthesized from the same monoacid [58]. 

The enantioselective synthesis in Scheme 13.22 is based on stereoselective reduction of an a, (3-unsaturated aldehyde generated from (—)-(.V)-limonene (Step A). The reduction was done by Baker s yeast and was completely enantioselective. The diastereoselectivity was not complete, generating an 80 20 mixture, but the diastere-omeric alcohols were purified at this stage. After oxidation to the aldehyde, the remainder of the side chain was introduced by a Grignard addition. The ester function... 

Solution-phase enantioselective synthesis of 437 and 438 thus achieved was also translated into solid-phase synthesis <2002TL8981>. The oxazolidinone 441 prepared from L-tyrosine methyl ester via 440 was attached to Merrifield resin to produce 442. Resin-bound 442 was converted to 443 (Scheme 98). 

The enantioselective synthesis of an allenic ester using chiral proton sources was performed by dynamic kinetic protonation of racemic allenylsamarium(III) species 237 and 238, which were derived from propargylic phosphate 236 by the metalation (Scheme 4.61) [97]. Protonation with (R,R)-(+)-hydrobcnzoin and R-(-)-pantolactone provided an allenic ester 239 with high enantiomeric purity. The selective protonation with (R,R)-(+)-hydrobenzoin giving R-(-)-allcnic ester 239 is in agreement with the... 

This procedure describes an efficient method for the synthesis of >99% enantiomerically pure ethyl glycidate from L-serine. Although preparation of potassium glycidate via cyclization of 3-bromo-2-hydroxypropionic acid,2 and from 3-chloro-2-hydroxypropionic acid (obtained by microbial reduction of chloropyruvic acid)3 was previously reported, the corresponding ethyl ester was never described. An enantioselective synthesis of the 2,3-epoxy acid by oxidation of 2,3-epoxypropanol has also been reported.4... 

Although it was also Henbest who reported as early as 1965 the first asymmetric epoxidation by using a chiral peracid, without doubt, one of the methods of enantioselective synthesis most frequently used in the past few years has been the "asymmetric epoxidation" reported in 1980 by K.B. Sharpless [3] which meets almost all the requirements for being an "ideal" reaction. That is to say, complete stereofacial selectivities are achieved under catalytic conditions and working at the multigram scale. The method, which is summarised in Fig. 10.1, involves the titanium (IV)-catalysed epoxidation of allylic alcohols in the presence of tartaric esters as chiral ligands. The reagents for this asyimnetric epoxidation of primary allylic alcohols are L-(+)- or D-(-)-diethyl (DET) or diisopropyl (DIPT) tartrate,27 titanium tetraisopropoxide and water free solutions of fert-butyl hydroperoxide. The natural and unnatural diethyl tartrates, as well as titanium tetraisopropoxide are commercially available, and the required water-free solution of tert-bnty hydroperoxide is easily prepared from the commercially available isooctane solutions. 

The cyclopropane aldehyde 156 was identified as a versatile chiral building block for the enantioselective synthesis of 4,5 disubstituted y-butyrolactones of type 158 or 159. Both enantiomers of 156 can be easily obtained in a highly diastereo- and enantioselective manner from fixran-2-carboxylic ester 154 using an asymmetric copper-catalyzed cyclopropanation as the key step followed by an ozonolysis of the remaining double bond (Scheme 25) [63]. Addition of... 

Ammonia lyases catalyze the enantioselective addition of ammonia to an activated double bond. A one-pot, three-step protocol was developed for the enantioselective synthesis of L-arylalanines 50 using phenylalanine ammonia lyase (PAL) in the key step (Scheme 2.20). After formation of the unsaturated esters 48 in situ via a Wittig reaction from the corresponding aldehydes, addition of porcine Ever esterase and basification of the reaction mixture resulted in hydrolysis to the carboxylic acids 49. Once this reaction had gone to completion, introduction of PAL and further addition of ammonia generated the amino acids 50 in good yield and excellent optical purity [22]. 

The most extensively developed allylboron reagents for enantioselective synthesis are derived from tartrate esters.40... 

Other similar lipase/esterase resolution processes have been developed such as the use of Bacillus that esterase to produce the substituted propanoic acids that are precursors of non-steroidal anti-inflammatory drags, snch as naproxen and ibuprofen etc., and the formation of chiral amines by Celgene. Other methods start from prochiral precursors and have the advantage that enantioselective synthesis allows the production of particular isomers in yields approaching 100%, rather than the 50% yields characteristic of resolution processes. For instance Hoechst have patented the production of enantiomers using Pseudomonas fluorescens lipase to either acylate diols or hydrolyse diacetate esters. 

A useful method for the diastereoselective and enantioselective synthesis of trans-and m-l,2-disubstituted cycloalkanecarboxaldehydes was devised by Koga et al.1990 starting from cycloalkanecarboxaldehydes. (S)-/er/.-Leucine ter/.-butyl ester, a highly effective chiral auxiliary reagent, could be recovered for recycling without any loss of optical purity in a reaction sequence similar to that in the acyclic synthesis of (202). 

The enantioselective synthesis of a somewhat more complex renin inhibitor starts with the reduction of the ester group in the chiral amino-ester (19-1) by means of diisobutyl aluminum hydride in the cold. The aldehyde product (19-2) is then reacted with prior isolation with the ylide from phosphonium salt (19-3) and a strong base... 

An alternate approach comprises replacing the pendant sugar by either a carbo-cyclic or a heterocyclic ring. The enantioselective synthesis starts by formation of the imide (45-3) by reaction of the aion from the chiral auxiliary (45-2), derived from S-phenylalaninol and the pentene ester (45-1). Treatment of the product with triethyl amine and the trifalate from dibutylboronic acid leads to the transient enol borate (45-4). Aldol addition of that enol to acrolein proceeds stereospecifically to the alcohol (45-5) due to the transfer of chirality from the chiral auxiliary. 

This variation was used for an enantioselective synthesis of anti-a-methyl-p-hydroxy esters using the silylketene acetal derived from (1R, 2S)-N-methylephed-rine-O-propionate (equation II).12... 

A large-scale, robust enantioselective synthesis of /i-subs(.Hu(.cd-/i-amino esters from aldehydes via imine formation with a chiral amme has been reported.21... 

Nevertheless, the use of chirally modified Lewis acids as catalysts for enantioselective aminoalkylation reactions proved to be an extraordinary fertile research area [3b-d, 16]. Meanwhile, numerous publications demonstrate their exceptional potential for the activation and chiral modification of Mannich reagents (generally imino compounds). In this way, not only HCN or its synthetic equivalents but also various other nucleophiles could be ami-noalkylated asymmetrically (e.g., trimethylsilyl enol ethers derived from esters or ketones, alkenes, allyltributylstannane, allyltrimethylsilanes, and ketones). This way efficient routes for the enantioselective synthesis of a variety of valuable synthetic building blocks were created (e.g., a-amino nitriles, a- or //-amino acid derivatives, homoallylic amines or //-amino ketones) [3b-d]. 

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