Oxazolines optically active, synthesis

Oxathiane dioxides lithiated 641 synthesis of 638, 647 Oxathiane oxides, synthesis of 352 Oxathiolane oxides, synthesis of 241 Oxaziridines 72, 254, 826 as optically active oxidizing agents 291 Oxazolidinones 826 Oxazolines 619, 788... 

In addition to the simple substitutions shown in Scheme 1, this reaction has been used in a variety of complex systems as a route to optically active substances. For example, use of chiral oxazolines in this coupling process has led to an asymmetric synthesis of (-)-steganone,3 podophyllotoxin,4 (-)-schizandrin,5 and (+)-phylictralin.6 The synthesis of (-)-schizandrin is sketched in Scheme 2. 

Lithiated chiral oxazolines have been shown to react with various electrophiles, generating a new asymmetric center with considerable bias. This process has led to the synthesis of optically active a-alkylalkanoic acids,47 n-hydroxy(methoxy)alkanoic acids,48 / -hydroxy(methoxy)alkanoic acids,49 n-substituted y-butyrolactones,50 and 2-substituted-l,4-butanediols (Fig. 2-4).50... 

Optically active namral and unnamral amino acids as well as various cyclic amino alcohols have been utilized in the synthesis of a wide variety of bis(oxazo-line) ligands. As previously mentioned, the first bis(oxazoline) ligands, py-box la-d, were synthesized by Nishiyama and co-workers in 1989. The common material for their syntheses was pyridine 2,6-dicarboxylic acid 19. Conversion of 19 to the acid chloride was achieved by treatment with thionyl chloride, as illustrated in Figure 9.4. This was followed by condensation with (5)-valinol in the presence of triethylamine. Conversion of the resulting bis(amidodiol) 20 to py-box-ip lb was achieved by sequential treatment of 20 with thionyl chloride at 50 °C followed by cyclization with aqueous sodium hydroxide in methanol to afford py-box-/p lb in 60% overall yield. The same synthetic scheme can be used to obtain the other... 

The first general method allowing the preparation of optically active 3,3-dialkylpropionic acids via asymmetric synthesis is based on chiral oxazolines.37-41 The a,3-unsaturated derivatives (41), accessible as pure ( )-isomers from (40) and the respective aldehydes (RCHO), undergo highly selective 1,4-additions in a variety of cases (Scheme 16) when treated with alkyl- or aryl-lithium reagents. The products... 

The efficient phase-transfer-catalyzed alkylation strategy with le was successfully applied by Jew and Park to the asymmetric synthesis of a-alkyl serines, using phenyl oxazoline derivative 53 as a requisite substrate [28]. The reaction is general, however, and provides a practical access to a variety of optically active a-alkyl serines through acidic hydrolysis of 54 (Scheme 5.26). 

Amino alcohols 127 can be easily converted into 2-oxazolines 128 by treatment with a,a-difluoroalkylamines 126. As the reaction proceeds under mild reaction conditions, the synthesis of optically active compounds has been accomplished <07S1528>. 

Evans et al. recently reported the use of structurally well-defined Sn(II) Lewis acids for the enantioselective aldol addition reactions of a-heterosubstituted substrates [47]. These complexes are readily assembled from Sn(OTf)2 and C2-symmetric bis(oxazoline) ligands. The facile synthesis of these ligands commences with optically active 1,2-diamino alcohols, which are themselves readily available from the corresponding a-amino acids. The Sn(II)-bis(oxazoline) complexes were shown to function optimally as catalysts for enantioselective aldol addition reactions with aldehydes and ketone substrates that are suited to putatively chelate the Lewis acid. For example, use of 10 mol % Sn(II) catalyst, thioacetate, and thiopropionate derived silyl ketene acetals added at -78 °C in dichloromethane to glyoxaldehyde to give hydroxy diesters in superb yields, enantioselectivity, and diastereoselectivity (Eq. 27). The process represents an unusual example wherein 2,3-ant/-aldol adducts are obtained stereoselec-tively. 

Oxazolines 175 and 176 are thus synthons for carboxylic acids this is another indirect method for the oc alkylation of a carboxylic acid, " representing an alternative to the malonic ester synthesis (10-67) and to 10-70 and 10-73. The method can be adapted to the preparation of optically active carboxylic acids by the use of a chiral reagent. Note that, unlike 170, 175 can be alkylated even if R is alkyl. However, the C=N bond of 175 and 176 cannot be effectively reduced, so that aldehyde synthesis is not feasible here. 

Reaction of lithiodithianes with acyl chlorides, esters or nitriles leads to the fOTination 1,2-dicarbonyl compounds in which one of the carbonyl groups is protected as the thioacetal. d76043j44 Optically active amino ketones of type (69) are inepared via acylation of dithiane with an oxazoline-protected (5)-serine methyl ester (Scheme 41). Optically active (5)-2-alkoxy-l-(l,3-dithian-2-yl)-l-propanones were prepaid by the reaction of the corresponding methyl (5)-lactate with 2-lithio-l,3-enantioselective synthesis of (-)-trachelanthic acid. Enantioselective synthesis of L-glyceraldehyde involves the acylation of a dithiane glycolic acid derivative followed by bikers yeast mediated reduction. ... 

Scheme 1. (Left) Synthesis of Polyaniline by Electropolymerization in the Presence of an Optically Active Acid and (Right) Structure of Oxazoline-Containing Polythiophene 29...

Copper complexes of chiral Pybox (pyridine-2,6-bis(oxazoline))-type ligands have been found to catalyze the enantioselective alkynylation of imines [26]. Moreover, the resultant optically active propargylamines are important intermediates for the synthesis of a variety of nitrogen compounds [27], as well as being a common structural feature of many biologically active compounds and natural products. Portnoy prepared PS-supported chiral Pybox-copper complex 35 via a five-step solid-phase synthetic sequence [28]. Cu(l) complexes of the polymeric Pybox ligands were then used as catalysts for the asymmetric addition of phenylacetylene to imine 36, as shown in Scheme 3.11. tBu-Pybox gave the best enantioselectivity of 83% ee in the synthesis of 37. 

The frans-oxazolines with high enantiomeric excess can readily be converted to optically active fhreo-P-hydroxy-a-amino acids without epimerization by acid hydrolysis. Moreover, the aldol reaction was applied to the total synthesis of Cyclosporin s unusual amino acid MeBmt [ 16], and to the asymmetric synthesis of D-threo- and D-eryfhro-sphingosine, important membrane components [ 17]. The [substrate]/[catalyst] ratio can be raised to 10,000/1 without significant loss of the stereoselectivity in the reaction of 3 with 3,4-methylenedioxybenzalde-hyde (91% ee, translcis=9 l9), indicating that the gold-catalyzed aldol reaction may provide a practical process to produce optically active fhreo-P-hydroxy-a-amino acids [6]. 

Methyl-l-phenylisoquinoline (380) is obtained when the oxazoline (379) is heated with phosphorus pentoxide. An efficient synthesis of alkylated and dialkylated acetic acids consists in the alkylation of 4,5-dihydro-oxazoline bound to polystyrene, followed by hydrolysis." The asymmetric synthesis of a series of a-alkylphenylacetic acids C H2 +i CHPhC02H ( = 1-5) from the chiral oxazoline (381) has been described. Another example of the use of oxazolines for asymmetric synthesis is the preparation of the optically active binaphthyl (383) from 1-lithionaphthalene and compound [382 R = (—)-menthyl]. The stereoselective formation of threo-dXdoX products (385 = Et, Pr, n-pentyl, etc from the chiral boron compound... 

In 1986 Ito and Hayashi pioneered the use of Au(l) homogeneous catalysts in asymmetric organic synthesis. Thus, the chiral ferrocenylphosphine/Au(l) catalyst precursor (3.55/3.56) formed in situ, catalysed asymmetric aldol reactions of an isocyanoacetate with aldehydes to produce optically active substituted oxazolines with high enantio- and diastereoselectivity (Scheme 3.22). The author suggested that the use of gold is essential for the high selectivity, a silver or copper catalyst being much less selective. 

Asymmetric synthesis of dialkylacetic acids can be done using a chiral oxazoline intermediate 4 derived from a readily available optically active amino alcohol. The... 

Bolm, C., Weickhardt, K., Zehnder, M. and Ranff, T. (1991) Synthesis of optically active bis(2-oxazolines) crystal structure of a l,2-bis(2-oxazolinyl)benzene ZnCL complex. Chem. Ber., 124, 1173-80. 

Anionic and Cationic Polymerizations o Radical Polymerization Advances o Coordination Polymerizations 0 Step-Growth Polymerization Advances 0 Synthesis of Tactic Polymers o Stereoblock Copolymers o Dispersion Polymerizations o Cellulosic Graft Copolymers o Diels-Alder Polymer Forming Reactions o A New Path To Phenolic Resins o Nitrogen Heterocycle Polymerizations o Optically Active Polymers o Poly (Phenylene Sulfide) o Poly (Aryl Ethers) o (Poly (Aryl Ether Sulfones) o Epoxy and Isocyanate Resin Replacement o Azlactone Functionalized Oligomers o Epoxy Resin-Isocyanate Reactions o Chelating Polymers o Oxazoline Functionalized Polymers o Poly (Alkyl Methacrylates) o Macromers... 

In 2006, Zhou s group reported a copper-catalyzed asymmetric synthesis (it was described in the paper as Friedel-Crafts-type reaction) using Al-sulfonyl aldimines with indoles to provide a simple approach to optically active 3-indolylmethanamine derivatives with high enantioselectivity. A bis-oxazoline-copper complex was used (Scheme 6.37) [50]. 

The highly enantioselective hydrogenation of unsaturated N-heterocyclic acids and 0-heterocyclic acids under H2 with CS2CO3 as additive and chiraliridium/spirophosphine oxazoline complexes as catalyst provide an efficient method for the preparation of optically active heterocyclic acids with up to 99% ee. The concise syntheses of (7 )-nipecotic acid and (/ )-tiagabine demonstrate that this catalytic asymmetric reaction has the potential for wide application in organic synthesis." ... 

A solid-phase method for the synthesis of optically active esters has been developed, which involves the alkylation of the polymer-bound oxazoline (34) (Scheme 26). An optical yield of 56% with chemical yields between 43 and 48% are obtained the polymer-bound amino-alcohols may be reisolated and used again. 

P. Rattanatraicharoen, K. Shintaku, K. Yamabuki, T. Oishi, K. Onimura, Synthesis and chiroptical properties of helical poly(phenylacetylene) bearing optically active chiral oxazoline Pendants. Polymer 53, 2567-2573 (2012)... 

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