1.3- Oxazolidines bonds

Thermolysis of the aziridine (446) in the presence of diphenylketene gave a mixture of the pyrrolidone (447 minor product) and the oxazolidine (448 major product). In this instance the preferential addition to the C=0 bond is explained in terms of steric effects (72CC199). Similar addition to diphenylacetaldehyde takes place with the same orientation and the oxazolidine (448a) was obtained. When the reaction of the aziridine with the aldehyde was carried out in the presence of hydrogen selenide a selenazolidine was obtained (72BSB295). 

An oxazolidine was used to protect the carbonyl group in an a,/3-unsaturated aldehyde during reduction of the carbon-carbon double bond by H2/Raney Ni. It... 

Apparently, cyclization involves the formation of open-chain intermediates 342, 343, further closing up to imidazolidines 344 and oxazolidines 345 which eliminate the secondary amine, thus leading to imidazolines 346 and oxazolines 347. The latter exist in the solution exclusively in the enolic forms 348, 349 which are stabilized by conjugation and intramolecular hydrogen bonds. 

In 2001, Braga et al. reported the synthesis of new chiral C2-symmetric oxazolidine disulfide ligands from (R)-cysteine and successfully applied them as catalysts in the asymmetric addition of ZnEt2 to various aldehydes (Scheme 3.23). In the presence of 2mol% of ligand, excellent enantioselectivities of up to >99% ee were obtained even with aliphatic aldehydes such as n-decanal or n-hexanal. These authors proposed that the active catalyst did not maintain its C2-symmetry during the reaction. The disulfide bond was probably cleaved in situ by ZnEt2. 

Azaacetals Oxazolidines are formed from ethanolamines and aldehydes or ketones. The C-O bond in oxazolidines can be cleaved selectively by catalytic hydrogenolysis (Scheme 4.15). 

Tejedor and coworkers have utilized a combination of two domino processes for a microwave-promoted synthesis of tetrasubstituted pyrroles [344]. The protocol combines two coupled domino processes the triethylamine-catalyzed synthesis of enol-protected propargylic alcohols and their sequential transformation into pyrroles through a spontaneous rearrangement from 1,3-oxazolidines (Scheme 6.183). Overall, these two linked and coupled domino processes build up two carbon-carbon bonds, two carbon-nitrogen bonds, and an aromatic ring in a regioselective and efficient manner. The tetrasubstituted pyrroles could be directly synthesized from the enol-protected propargylic alcohols and the primary amines by microwave irradia-... 

Microwave irradiation in solvent-free conditions induces the cleavage of the 2,3-bond of 2-aroyl-aziridines 135 to give an azomethine ylide intermediate, which subsequently undergoes cycloadditions to a multiple bond and leads to oxazolidine, imidazoline, naphthooxazole and pyrroline derivatives 136 in good yields (Scheme 9.41) [32b], Reactions were performed at atmospheric pressure in an Erlenmeyer flask placed in a commercial domestic oven. The reactions were complete in 10-15 min while the conventional method requires 18-20 h. 

On the other hand, 4-vinylidene-l,3-oxazolidin-2-one 26 undergoes a facile [2 + 2]-cycloaddition with electron-deficient olefins regioselectively at the terminal double bond to furnish methylenecyclobutane derivatives [25]. 

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-. 

ALKYLATION OF PEPTIDE BONDS TO DECREASE AGGREGATION OXAZOLIDINES AND THIAZOLIDINES (PSEUDO-PROLINES)... 

Aryl or alkyl substituents on the exocyclic double bond st r the regioselec-tivity towards the formation of i oxazolidine-4-spirocyclopropanes 274-276 (Table 22, entries 1-3). A complete reversal of regioselectivity to 277-279 was observed in the reactions of methoxycarbonyl substituted methylenecyclo-... 

Like carbene insertions into carbon-hydrogen bonds, metal nitrene insertions occur in both intermolecular and intramolecular reactions.For intermole-cular reactions, a manganese(III) meio-tetrakis(pentafluorophenyl)porphyrm complex gives high product yields and turnovers up to 2600 amidations could be effected directly with amides using PhI(OAc)2 (Eq. 51). The most exciting development in intramolecular C—H reactions thus far has been the oxidative cychzation of sulfamate esters (e.g., Eq. 52), as well as carbamates (to oxazolidin-2-ones), ° and one can expect further developments that are of synthetic... 

The Pd-catalyzed reaction of 5-vinyl-l,3-oxazolidin-2-ones 260 at 65-70°C and 65 atm of CO in ethanol gave 5-lactams 263 in fairly good to high yields (Scheme 38).As Scheme 38 illustrates, this decarboxylative carbonylation reaction is likely to involve (i) the cleavage of the allylic C-O bond of 260 to form tr-allyl-Pd complex syn-2(A, (ii) isomerization to anti-2(A, (iii) decarboxylation forming 7r-allyl-Pd-amine complex 262, and (iv) CO insertion to 262 followed by aminolysis to yield 5-lactam 263. 

This has been shown to work well for a diverse set of libraries (see Note 2) (4). In Fig. 17.3, the offset is calculated for the oxazolidine library for properties related to Lipinski s rule of five (8) the number of hydrogen bond acceptors (HBA), the number of hydrogen bond donors (HBD), the number of non-hydrogen atoms (NHA), and the calculated log P (9). 

The preferential addition to the C = O bond is explained in terms of steric effects (72CC199). Similar addition to diphenylacetaldehyde takes place with the same orientation to give the oxazolidine (228). 

The bromocyclization of A/,jV-dialkylaminomethyl ethers of allyl and propargyl alcohols to form oxa-zolidinium salts has been reported, but not used in synthesis.255 The heterocyclization of /V-acylamino-methyl ethers with mercury salts has been used for stereoselective synthesis of a variety of 1,2-amino alcohol systems. These cyclizations form rans-4,5-dialkyl oxazolidine products with good to excellent stereoselectivities (equation 120 and Table 33). As shown by entry 5, 6-endo cyclization predominates (6 3) with an internal double bond of ( )-configuration, but this mode of cyclization is reduced with substrates containing a (Z) double bond and/or allylic oxygen substitution (Table 33, entries 6-9). 

P2i Z = 2 Dx = 1.577 R = 0.033 for 1,041 intensities. The compound is a hydrolysis product of 5-azacytidine. The conformation of the D-ribose part is 4E, with C-4 endo, similar to that observed for some a-nucleosides. The oxazolidine ring is planar. The dihedral angle between the two planes, as defined by the torsion angle 0-4-C-l-C-2-0-2 about the common C-l-C-2 bond, is +111°. The orientation of the primary alcohol group is gauche /gauche. 

Other dipolarophiles have been tested leading to pyrrolidines (from vinyl sulfones),219 oxazolidines (from ketones) and thiazolidine (from a thioketone) in moderate to good yields. Noteworthy is the isolation of two adducts from ethoxycrotonaldehyde a pyrrolidine carbaldehyde implying cycloaddition onto the ethylenic double bond and an oxazolidine resulting from the cycloaddition on the carbonyl moiety of the dipolarophile.219 438... 

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