Oxazolines acylation

Unsaturated acyl derivatives of oxazolidinones can be used as acceptors, and these reactions are enantioselective in the presence of chiral to-oxazoline catalysts.321 Silyl ketene acetals of thiol esters are good reactants and the stereochemistry depends on the ketene acetal configuration. The Z-isomer gives higher diastereoselectivity than the Zf-isomer. 

An alternative procedure for the synthesis of aliphatic 2-substituted oxazoline hydroxamates was described by Pirrung and colleagues in the context of preparing inhibitors of E. coli LpxC zinc amidase [378], As shown in Scheme 6.210 a, the protocol involved the cyclization of suitable amides, formed in situ by acylation of a serine-derived 0-2,4-dimethoxybenzyl (DMB)-protected hydroxamate. The cyclization... 

Reagent control This involves the addition of a chiral enolate or allyl metal reagent to an achiral aldehyde. Chiral enolates are most commonly formed through the incorporation of chiral auxiliaries in the form of esters, acyl amides (oxazolines), imides (oxazolidinones) or boron enolates. Chiral allyl metal reagents are also typically joined with chiral ligands. 

The copper complex of these bis(oxazoline) compounds can also be used for hetero Diels-Alder reactions of acyl phosphonates with enol ethers.43 5 A favorable acyl phosphonate-catalyst association is achieved via complexation between the vicinal C=0 and P=0 functional groups. The acyl phosphonates are activated, leading to facile cycloaddition with electron-rich alkenes such as enol ethers. The product cyclic enol phosphonates can be used as building blocks in the asymmetric synthesis of complicated molecules. Scheme 5-36 shows the results of such reactions. 

Asymmetric Diels—Alder catalysis was more successful with dication-like versions of the Zr-EBTHI system, and using conformationally better defined acyl-oxazoline dieno-philes. The bis(triflate) [Zr(EBTHI)(OTf)2] (Scheme 8.47) induced high levels of ee (>90%) in the cycloaddition to cyclopentadiene at low temperatures, especially in the polar solvent 2-nitropropane [87]. 

In a similar fashion, the cationic polymerization of 2-oxazolines has been extensively studied and was found to provide the first verified entry to linear-poly(alkyleneimine) architectures. These acylated polymers were first recognized as precursors to linear poly(ethyleneimines) in the early 1960s [25]. Hydrolysis experiments demonstrated that deacylation of these products to linear PEI was possible. The original polymerization mechanism proposed by Tomalia et al. 

FIGURE 6.5 Transfer of acyl between the amino and hydroxyl groups of seryl. (A) Deprotonation of O-acylseryl- induces oxazolidine formation, which is followed by (B) rearrangement to A-acylseryl-. (C) Protonation of the carbonyl of A-acylseryl- by mineral acid results in dehydration to the oxazoline, which is followed by hydrolysis (D) at the double bond giving protonated O-acylseryl-. 

Immobilization of TADDOL-derivatives to silica and treatment with various tita-nium(IV) salts furnished a catalytic system (38) which was utilized in [2-1-3] cycloadditions of diphenylnitrone and acylated oxazolidinone to yield oxazolines (Scheme 4.23) [65]. It is noteworthy that the ligand X has an impact on the outcome of this cycloaddition. While the dichloro catalyst affords the exo-adduct in good yield and with a high stereoselectivity, the corresponding tosyloxy catalyst preferentially affords the endo-cycloadduct. The efficiency of the process is comparable to those obtained with the analogous soluble catalysts. The catalyst, however, had to be recycled prior to each experiment. 

C, and then three molecular equivalents of acetyl chloride and triethy-lamine were added. Three types of acetylated materials, 11, 12, and 13, were isolated accompanied by a small amount of thioketone 7 and thioamide 9 (Scheme 8 and Table 6). All of the acetylated materials showed optical activity. For the reaction of 6a, 84% ee of 2-(acetylthio)aziridine 11a, 50% ee of 4-(acetyl-thio)oxazoline 12a, and 20% ee of 4-(acetylthio)oxazolidin-2-one 13a were obtained in 39,10, and 16% yields, respectively. In the reaction of 6b,c, the corresponding optically active materials 11-13 were obtained as shown in Table 9. The formation of oxazoline 12 involves the rearrangement ofAT-acyl aziridines, which occurs by intramolecular attack of the carbonyl oxygen at the ring carbon to cause rupture of the system. 

Synthesis of a Linear, iV-Acylated Polyethyleneimine Through Cationic Polymerization of 2-Methyl-2-Oxazoline in Bulk... 

It was shown previously that saturated 5(4//)-oxazolones or 2-oxazolm-5-ones with only one substituent at C-4 can be considered as the tautomeric form of saturated 5(2//)-oxazolones or 3-oxazolin-5-ones. These compounds can also be considered as amino acid derivatives and, indeed, cyclization procedures are the most commonly used to prepare these compounds. The cyclization reaction employs a variety of cyclodehydrating agents and the general method is shown in Scheme 7.23, with an A-acyl-a-amino acid being the most typical starting material used. In this way, 5(4//)-oxazolones derived from most natural amino acids 99 (R3 = H) have been obtained by heating the corresponding A-acyl derivatives in the presence of acetic anhydride. 

A similar reaction of vincinal aromatic or heterocyclic diamines 104 with 2-benzoylamino-3-chloropropenoic acid 102 resulted in sprro-2-oxazolines fused to a pyrazinone nucleus 108. It is believed that the enamide 102 first isomerizes to the A-acyl imine 103 followed by Michael addition of the diamine 104. The resulting Michael adduct 105 cyclizes to 106 or 107 either of which leads to the same oxazoline 108. Single-crystal X-ray confirmed the structure of 108. Unsymmetrical diamines gave two isomeric products with the predominant product... 

Langlois and co-workers ° developed a stereoselective hetero-Claisen rearrangement of camphor-based oxazoline A -oxides 300, available from hydroxylami-noisobomeol 298 and orthoesters 299. The rearrangement, initiated by acylation of... 

Acyl-2-phenyloxazole derivatives undergo a reductive photocyclization in the presence of sodium borohydride to generate a bicychc oxazoline with a cis-fused pyridinone ring 307. The stereochemistry of the product is consistent with hydride attack from the less hindered surface of the cyclic intermediate 306. The oxazoline containing pyridinone is a key intermediate used for the synthesis of pseudodisto-mins 308 (Scheme 8.85, p. 415). ° ... 

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