Esters, 2-hydroxy enantioselective synthesis

M. Horikawa, J. Bush-Petersen, E. J. Corey, Enantioselective Synthesis of P-Hydroxy-a-amino Acid Esters by Adol Coupling Using a Chiral Quaternary Ammonium Salt as Catalyst , Tetrahedron Lett. 1999, 40, 3843-3846. 

Perlmutter used an oxymercuration/demercuration of a y-hydroxy alkene as the key transformation in an enantioselective synthesis of the C(8 ) epimeric smaller fragment of lb (and many more pamamycin homologs cf. Fig. 1) [36]. Preparation of substrate 164 for the crucial cyclization event commenced with silylation and reduction of hydroxy ester 158 (85-89% ee) [37] to give aldehyde 159, which was converted to alkenal 162 by (Z)-selective olefination with ylide 160 (dr=89 l 1) and another diisobutylaluminum hydride reduction (Scheme 22). An Oppolzer aldol reaction with boron enolate 163 then provided 164 as the major product. Upon successive treatment of 164 with mercury(II) acetate and sodium chloride, organomercurial compound 165 and a second minor diastereomer (dr=6 l) were formed, which could be easily separated. Reductive demercuration, hydrolytic cleavage of the chiral auxiliary, methyl ester formation, and desilylation eventually led to 166, the C(8 ) epimer of the... 

The enzyme recLBADH is the first catalyst that has been found to allow the highly regio- and enantioselective synthesis of 5-hydroxy-P-keto esters by reduction of the respective diketo esters. This enzymatic reaction is of enormous preparative value. The substrates are readily available by acylation of P-keto ester bisenolates and the reaction only requires a simple batch technique which is easy to scale up. Reduction of the chlorinated compound la has been performed routinely on a 75 g scale in our laboratory (8 L fed batch), yielding (S)-2a in an isolated yield of 84% [10]. 

The biotechnological synthesis of lactones has reached a high standard. Besides microbial production, lactones can also be enzymatically produced. For instance, a lipase-catalysed intramolecular transesterification of 4-hydroxy-carboxylic esters leads enantioselectively (ee>80%) to (S)-y-lactones the chain length may vary from C5 to Cl 1 [13]. y-Butyrolactone can be produced in that way with lipase from Mucor miehei [30]. 

Reactions using catecholborane proceed smoothly in toluene (Scheme 16) (40). The utility of catalytic hydroboration of ketones has been demonstrated by the efficient enantioselective synthesis of a series of biologically active compounds (41). Scheme 17 shows some compounds prepared by using this method. Enantioselective reduction of trichloro-methyl ketones is a general route to a-amino acids and a-hydroxy esters it also allows ready synthesis of a precursor to the carbonic anhy-drase inhibitor MK-0417 (42). 

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... 

Wulff and his collaborators reported, in 1989, the preparation of imprinted polymers able to perform enantioselective synthesis [11, 12]. The imprinting complex was prepared by reacting 3,4-di-hydroxy-phenyl-alanine methyl-ester (l-DOPA methyl ester) (16) with the 4-vinyl-salicylaldehyde (17) to form the corresponding Schiff s base (18), which was further reacted with the 4-vinyl-phenyl-boronic acid (19) to afford to the corresponding ester (20) (Scheme 4). The imprinting complex obtained was then polymerised and the template removed. The resulting polymers were incubated with sodium glycinate to allow formation... 

Jew and Park achieved a highly enantioselective synthesis of (2S)-a-(hydroxy-methyljglutamic acid, a potent metabotropic receptor ligand, through the Michael addition of 2-naphthalen-l-yl-2-oxazoline-4-carboxylic acid tert-butyl ester 72 to ethyl acrylate under phase-transfer conditions [38]. As shown in Scheme 5.36, the use of BEMP as a base at —60 °C with the catalysis of N-spiro chiral quaternary ammonium bromide le appeared to be essential for attaining an excellent selectivity. 

Conversion ofpropargyl esters to dihydrofurans1 (11,469-470). The reaction can be used for an enantioselective synthesis of dihydrofurans. Thus reduction of 3-hydroxy-l-alkynyl ketones (2) with Midland s reagent, (+)-l, provides (4S)-2-bu-tyne-l,4-diols (3) in 84-91% ee. Monoacylation (4) followed by treatment with... 

Oxidation of the dienolate of (17) with (+)-( ) affords a-hydroxy ester (18), a key intermediate in the enantioselective synthesis of the antibiotic echinosporin (eq 19) whereas oxidation of enolates derived from 1,3-dioxin vinylogous ester (19) gives rise to both a - and y-hydroxylation depending on the reaction conditions (eq 20). With (+)-( ) the lithium enolate of (19) gives primarily the a -hydroxylation product (20), while the sodium enolate gives )/-hydroxylation product (21). Only low levels of asymmetric induction (ca. 16% ee) are found in these oxidations. Birch reduction products are also asymmetrically hydroxylated in situ by (+)-( ) (eq 21). ... 

The diastereo- and enantioselective synthesis of both stereoisomers of a-alkoxy-p-hydroxy-p-methyl thioesters is also attained by reaction of enol silyl esters possessing alkoxy groups at the 2-position with a tin(II) Lewis acid and the chiral diamine 1 as promoters (eqs 30 and 31). ... 

By judicious choice of chiral auxiliary-reagent pairs, it has been possible to extend this chemistry to the enantioselective synthesis of p-hydroxy-a-methyl-carboxylic acid derivatives having either anti or syn stereochemistry (Schemes 24 and 25). For example, the boron azaenolate obtained upon reaction of (65) with diisopinocamphenylboryl triflate reacts with a series of aldehydes to provide adducts that are readily converted to the anti methyl esters (66) in good overall yields (Scheme 24). The anti.syn ratios for these reactions are typically >9 1, and the percentage enantiomeric excesses for the anti adducts are in the range of 77-85%. On the other hand, the boron azaenolate derived from oxazoline (61c) and 9-borabicyclononane triflate reacts with aldehydes to give adducts that can be converted into the methyl esters of the jyn-carboxylic acids (67 Scheme 25). The symanti ratios in these reactions are typically... 

Ene reactions. The enantioselective synthesis of a-hydroxy esters from ene reaction of glyoxylate is effective using vinyl chalcogenides and allylsilanes. The reaction of fluoral also attains a high level of enantio- and diastereoselectivities. Chiral catalysts that contain substituents in the BINOL moiety have been evaluated. 

E-a,6-unsaturated esters possessing a chiral sulphoxide substituent at the -position has been developed for the enantioselective synthesis of E-Y-hydroxy-a,8-unsaturated esters.11 The asymmetric cyclization of 7,7-dimethyl-6-7-unsaturated aldehydes to chiral... 

Furthermore, Pd(Il) eomplexes catalyze asymmetric ene and Diels-Alder reactions. Mikami and co-workers reported enantioselective synthesis of a-hydroxy esters by the ene reaction of glyoxylate 27 using a chiral Pd catalyst. They obtained the (/ )-hydroxy ester 28 with 88% ee in 97 % yield by the reaetion of methylenecyelohexane (26) with ethyl glyoxylate (27) at 60 °C using the eadonic Pd(II) eonqilex of (5)-Tol-BINAP [7]. 

In the 1980s, Hiroyuki Akita and Takeshi Oishi published an enantioselective synthesis of oudemansin A, where a jS-keto-ester is reduced stereoselectively to the jS-hydroxy-ester with Candida albicans. After chromatographic purification from small amounts of diastereomers, the ester is then homologised in a classical reduction and cyanide substitution sequence. The remainder of the synthesis for establishing the acrylate system follows the previously described methodology. [53-55]... 

Righi G, Rumboldt G (1996) Stereoselective Preparation of Syn o -Hydroxy-/5-amino Ester Units via Regioselective Opening of a,/5-Epoxy Esters Enantioselective Synthesis of Taxol C-13 Side Chain and Cyclohexylnorstatine. J Org Chem 61 3557... 

Bonini, C., R Pucci, R. Racioppi, and L. Viggiani Enzyme Catalysed Lactonization of 3,5-Dihydroxy Esters Enantioselective Synthesis of Naturally Occurring 3-Hydroxy-5-decanolide, (-)-Massoialactone and 3-Hydroxy-5-eicosanolide. Tetrahedron Asymmetry, 3, 29 (1992). 

The enantioselective synthesis of a-hydroxy phosphonates 26 could be accomplished with excellent results independently on the nature of ketone substituent R by reaction of acetone (3a) with a-keto phosphonates 25 (Scheme 4.10). The size of ester moiety had a little effect, with the best enantioselectivities being achieved for isopropyl derivatives [66]. 

---