Catalysts threonine

More recent developments are the SerPHOX catalyst 22 [20] and the Thre-PHOX catalyst 23 [21] (Fig. 29.9), derived from serine or threonine, respectively (Scheme 29.4). 

Since the discovery of the CBS catalyst system, many chiral //-amino alcohols have been prepared for the synthesis of new oxazoborolidine catalysts. Compounds 95 and 96 have been prepared93 from L-cysteine. Aziridine carbi-nols 97a and 97b have been prepared94 from L-serine and L-threonine, respectively. When applied in the catalytic borane reduction of prochiral ketones, good to excellent enantioselectivity can be attained (Schemes 6-42 and 6-43). 

In a recent modification of the second synthesis (50S) effected for fluvibactin (45) an o-xylene protection group was proposed (reaction of 2,3-dihydroxy-benzoic acid methyl ester with 1,2-di(bromomethyl)benzene) which could be removed later by hydrogenolysis. The formation of the oxazoline ring from protected DHB-L-threonine methyl ester was achieved with Mo(VI) catalysts (e.g. (NH4)2Mo04) without affecting the chiral centers. Derivatization of the primary amino groups of norspermidine with the protected DHB methyl ester was catalyzed by Sb(OC2115)3. 

Ketone donors bearing a-heteroatoms are particularly useful donors for the enamine-catalyzed aldol reactions (Scheme 18). Both anti and syn aldol products can be accessed in remarkably high enantioselectivities using either proline or proline-derived amide, sulfonamide, or peptide catalysts. The syn selective variant of this reaction was discovered by Barbas [179]. Very recently, Luo and Cheng have also described a syn selective variant with dihydroxyacetone donors [201], and the Barbas group has developed improved threonine-derived catalysts 71 (Scheme 18) for syn selective reactions with both protected and unprotected dihydroxyacetone [202]. 

A corresponding ThrA has been detected in a number of strictly anaerobic bacteria, and the enzyme from Clostridium pasteurianum has been purified and shown to be highly selective for L-threonine 150 [457]. A corresponding L-specific catalyst has also been purified and crystallized from cells of the yeast Candida humicola. Very recently, the latter enzyme was reinvestigated for synthetic purposes and found to have a very broad substrate tolerance for the aldehyde acceptor, notably including variously substituted aliphatic and aro-... 

The intermolecular Diels-Alder reaction between the dibromoenone (111) and dienes (112) provides access to bicyclo[5.4.0]undecane systems (113) that are common core structures of many natural products (Scheme 32).118 The alio-threonine-derived O-(/ -biphenyl carbonyl oxy)-/i-phenyloxazaborolidi none catalyses the enan-tioselective Diels-Alder reaction of acyclic enones with dienes.119 The reversal of facial selectivity in the Diels-Alder cycloaddition of a semicyclic diene with a bro-moenone was induced by the presence of the bromo substituent in the dienophile.120 Mixed Lewis acid catalyst (AlBr3/AIMe3) catalyses the Diels-Alder reaction of hindered silyloxydienes with substituted enones to produce highly substituted cyclohexenes.121 Chiral /V-enoyl sultams have been used as chiral auxiliaries in the asymmetric Diels-Alder reactions with cyclopentadiene.122... 

Figure 2.8 Catalysis by the protonated amine could explain the stereochemistry of threonine and 0/0-threonine synthesis by our catalyst 46 at low pH. (Reprinted from Ref. 47. Copyright 1994 American Chemical Society.)...

The traditional method for preparing (m-butyl ethers involves reacting a large excess of isobutene with a solution of the alcohol in dichloromethane in the presence of concentrated sulfuric acid, p-toluenesulfonic acid or phosphoric acid and the method is effective for protecting the side chain hydroxyl functions of serine, threonine [Scheme 4.123], and tyrosine.223 224 A more convenient method involving use of Amberlyst H-15 resin in hexane as the acid catalyst deserves wider attention.217... 

Several new ligands containing the oxazoline nucleus were synthesized in enantiopure form. Compounds of general structure 165 were obtained from L-serine or L-threonine and found application as catalysts for the zinc addition to aldehydes <03TA3292> or were derived from P-amino alcohols and used in diethylzinc addition to A -(diphenylphosphinoyl) imines <03JOC4322>. Also, compound 166 was derived from a commercially available amino acid and afforded good selectivity in allylic alkylation <03TL6469>. 

Rhodium and ruthenium complexes of CHIRAPHOS are also useful for the asymmetric hydrogenation of p-keto esters. Dynamic kinetic resolution of racemic 2-acylamino-3-oxobutyrates was performed by hydrogenation using ((5,5)-CHIRAPHOS)RuBr2 (eq 3). The product yields and enantiomeric excesses were dependent upon solvent, ligand, and the ratio of substrate to catalyst. Under optimum conditions a 97 3 mixture of syn and anti p-hydroxy esters was formed, which was converted to o-threonine (85% ee) and D-allothreonine (99% ee) by hydrolysis and reaction with propylene oxide. 

The tert-butyl ethers of serine and threonine are available by tert-butylation of various starting materials, e.g. Z-Ser-OMe/Z-Thr-OMe,P l Z-Ser-ONbz/Z-Thr-ONbz,P l and H-Ser-OMe TosOH/H-Thr-OMe -TosOHt l (see also Table 3). Analogous to benzyl ether formation, the tert-butyl ethers can also be produced via 4-substituted 2,2-difluoro-l,3,2-ox-azaborolidin-5-ones.t In most cases, isobutylene with 4-toluenesulfonic add, or a concentrated inorganic acid is used as catalyst for tert-butylation. The use of Fmoc-Ser(tBu)-OH and Fmoc-Thr(tBu)-OH in solid-phase peptide synthesis is very well established. These annino acid derivatives can be synthesized either by introduction of the Fmoc group into H-Ser(tBu)-OH and H-Thr(tBu)-OH or by tert-butylation of the Fmoc-protected serine and threonine (Table 3). ... 

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