4.5- disubstituted oxazolines

A -acylaziridines substituted with an electron-withdrawing group produce a 2,4-disubstituted oxazoline as the major product. Borontrifluoride etherate (BF3 OEt2) has also been used successfully for an Al-benzoyl, but not an N-acetyl-substituted aziridine (Scheme 8.58). ... 

N-Acylated amino acids, in the presence of watercoupling reagents (dicyclohexylcarbodiimide or the excess of TFAA), form other cyclic derivatives — azlactones (2,4-disubstituted oxazolin-5-ones) ... 

If ring expansion of 68 (Ri = electron-withdrawing group) was affected by a nucleophile then a 2,5-disubstituted oxazoUne was produced. However, rearrangement of 68 (Ri = electron-donating group) under similar conditions affords a 2,4-disubstituted oxazoline 69 (Scheme 1.21). 

For secondary (3-hydroxy amides, the ring closure occurs via an Sn2 mechanism with complete inversion at carbon bearing the hydroxyl group. Thus, both cis- and trans-4,5-disubstituted oxazolines can usually be obtained reliably. Representative examples are shown in Table... 

About 30 years ago van Leusen and co-workers pioneered the condensation of TosMIC with aldehydes and ketones to prepare 4,5-disubstituted oxazolines that eliminate toluenesulfinic acid to yield 5-substituted oxazoles. This process continues today as an important method for constructing such analogues, as evidenced by the following examples. 

Tanaka and Kuriyama " prepared cii-4,5-disubstituted-oxazolines by catalytic hydrogenation of 2-amino-4,5-disubstituted oxazoles using PtOa or Pd/C. The authors isolated ring cleavage products from reactions employing a high catalyst load. 

When the D-o//xazoline 41 (Scheme 6) was treated with di-/-butyl oxaloacetate under basic conditions, the lactone 42 was produced, together with its C-4 epimer. Both 42 and its epimer had undergone epim sation at C-S to give the irans-disubstituted oxazoline. Acidic hydrolysis and... 

More recent examples have employed a milder reagent system, triphenyl-phosphine and dibromotetrachloroethane to generate a bromo-oxazoline, which is subsequently dehydrohalogenated. Wipf and Lim utilized their method to transform intermediate 11 into the 2,4-disubstituted system of (+)-Hennoxazole k Subsequently, Morwick and coworkers reported a generalized approach to 2,4-disubstituted oxazoles from amino acids using a similar reagent combination, triphenylphosphine and hexachloroethane. ... 

Chiral //A(oxazolinc) ligands disubstituted at the carbon atom linking the two oxazolines by Frechet-type polyether dendrimers coordinated with copper(II) triflate were found to provide good yields and moderate enantioselectivities for Mukaiyama aldol reactions in water that are comparable with those resulting from the corresponding smaller catalysts.291 AgPF6-BINAP is very active in this reaction and the addition of a small amount of water enhanced the reactivity.292... 

Hydrosilylation of 1,6-dienes accompanied by cyclization giving a five-membered ring system is emerging as a potential route to the synthesis of functionalized carbocycles.81,81a,81b 82 As its asymmetric version, diallylmalonates 86 were treated with trialkylsilane in the presence of a cationic palladium catalyst 88, which is coordinated with a chiral pyridine-oxazoline ligand. As the cyclization-hydrosilylation products, //ww-disubstituted cyclopentanes 87 were obtained with high diastereoselectivity (>95%), whose enantioselectivity ranged between 87% and 90% (Scheme 25).83 83a... 

In addition to P,N ligands, the carbenoid-oxazoline catalysts 47 (Fig. 30.10) were used to hydrogenate test substrates 36-39, as well as substrates 48 and 49, which were hydrogenated in 93% ee and 84% ee, respectively [21]. These catalysts were also used to hydrogenate 1,1-disubstituted alkenes (see Section 30.2.1). 

In addition to the reactions discussed above, a,//-unsaturated oxazolines can also act as chiral electrophiles to undergo conjugated addition of organolithium reagent to give optically active / ,/ -disubstituted carboxylic acids.52 The vinyl oxazolines 48 are prepared using the two methods outlined in Scheme 2-27. 

Lowenthal and Masamune (44) investigated the cyclopropanation of trisubsti-tuted alkenes leading to a chrysanthemic acid synthesis. They found that ligand 50c provided poor selectivities in this case (24% de for the trans isomer). Substitution in the 5 position of the oxazolines leads to increased selectivities, with excellent results provided by the BHT ester (94 6, 94% ee), Eq. 32. This ligand proved to be applicable to other trisubstituted and several cis-disubstituted alkenes, providing the corresponding cyclopropanes in ee values of 82-95%. These authors note that catalysts generated from CuOTf, CuOf-Bu, and Cu(II) precursors (with activation) provided similar yields and enantioselectivities. 

The reaction of ketoximes 235 with dimethyl carbonate in the presence of K2CO3, carried out in an autoclave at 180-190 °C, afforded 3-methyl-4,5-disubstituted 4-oxazolin-2-ones 236 (equation 102). The formation of compounds 236 occurred via [3,3]sigma-tropic rearrangement of intermediates of the oxime methylated with dimethyl carbonate. 

Oxidation of conjugated dienes in CH3CN-NaC104 in the presence of 1,3-dimethylurea gives a mixture of the possible 4,5-disubstituted 1,3-di-methylimidazolidin-2-ones in about 40% yield.103 Anodic oxidation of 2,4-hexadiene, 1,3-butadiene, and 1,3-cyclohexadiene in CH3CN-H20-NaC104 yields diols, 2-oxazolines, and 3-pyrrolines.104 The product distribution is influenced by the supporting electrolyte. 

Chiral-trans-l,2-disubstituted-l,2-dihydronaphthalenes (cf. 12, 310-311).1 Addition of an organolithium to chiral (l-naphthalyl)oxazolines (2, derived from 1) followed by quenching with CF3COOH results in the salt 3. This product is reduced by LiAlH4 to a single frans-l,2-diaxial diastereomer 4. 

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