Oxazolidines, substituted

One of the limitations of the Warren s adaptation of Homer-Wittig olefina-tion, the failure of the (Z)-selective route when the alkene has a branched chain substituent, has now been overcome. Reduction of the p-ketophosphonates carrying a-branches, e.g. (112) and (113), with sodium borohydride and cerium chloride gives excellent a / -stereoselectivity and hence (Z)-alkene on base-induced elimination. Enantioselective synthesis of both jy -(115) and anti- ll) P-hydroxy-phosphine oxides has been achieved with up to 90% e.e. through two separate approaches. The jyn-isomer was obtained by reduction of the corresponding ketone (114), while the anti-isomer is the product of the reaction of the oxazolidine substituted aldehyde (116) with lithiated diphenylmethyl-phosphine oxide (Scheme 10). A new, highly stereoselective approach to trisubstituted alkenes has been reported. Cerium(III) chloride-promoted... 

Chiral Auxiliary-hased Epoxidation of Substituted Alkenes. High diastereoselectivities were found for the m-CPBA or dimethyldioxirane epoxidation of chiral oxazolidine-substituted alkenes bearing a strongly basic urea group (eq 29). However, in most cases, the diastereoselectivities were superior with dimethyldioxirane. 

Intramolecular reaction of the allenyl carbamate 5 in the presence of a large excess of allylic chloride catalyzed by Pdi(dba)3 or PdCl2(PhCN)2 affords the substituted oxazolidin-2-one 6. Since the reaction is catalyzed by both Pd(II) and Pd(0), its mechanism is not dear[3]. 

LiBF4, wet CH3CN, 96% yield.Unsubstituted 1,3-dioxolanes are hydrolyzed only slowly, but substituted dioxolanes are completely stable.This reagent proved excellent for hydrolysis of the dimethyl ketal in the presence of the acid-sensitive oxazolidine. ... 

To investigate die effect of die substduents in die atenediiolaie structure, four diffetendy substituted copper arenediiolates, 25-28, were tested as catalysts, but very low ees were obtained in all cases [34]. Hie oxazolidine complex 26, developed by Pfaltz et al. [36] and used successfully in asymmetric conjugate adddion re-... 

Dimedone and related compounds behave as carbon nucleophiles towards oxazines and oxazolidines leading to the octahydroxanthene derivative (3). In the presence of stoichiometric quantities of reactive C-nucleophiles, such as substituted acetonitriles, 2,3-disubstituted partially reduced 4ff-l-benzopyrans result <96T14273>. 

The 8-methyl-8,14-cycloberbine 364, derived from the protoberberine 324 via the betaine 363, was reduced with sodium borohydride or lithium aluminum tri-tert-butoxyhydride to give a diastereoisomeric mixture of cis-and trans-alcohols (7.8 1 or 1 7.8, respectively) (Scheme 64).t)n exposure to formaldehyde the mixture underwent N-hydroxymethylation and subsequent intramolecular substitution on the aziridine ring to give the oxazolidine 365. Removal of the hydroxyl group in 365 was accomplished by chlorination followed by hydrogenolysis with tributyltin hydride. Reductive opening of the oxazolidine 366 with sodium cyanoborohydride afforded ( )-raddeanamine (360), which has already been converted to ochotensimine (282) by dehydration. 

In NRPs and hybrid NRP-PK natural products, the heterocycles oxazole and thiazole are derived from serine and cysteine amino acids respectively. For their creation, a cyclization (or Cy) domain is responsible for nucleophilic attack of the side-chain heteroatom within a dipeptide upon the amide carbonyl joining the amino acids [61]. Once the cyclic moiety is formed, the ring may be further oxidized, to form the oxazoline/thiazoline, or reduced, to form oxazolidine/thiazolidine (Figure 13.20). For substituted oxazoles and thiazoles, such as those... 

A very simple and straightforward access to enantiopure substituted pyrrolidines and piperidines was obtained by reaction of phenylglycinol 178 with co-chloroketones 179. The intermediate oxazolidines 180 were then easily converted into the desired compounds <00EJO1719>. Compound 182 was obtained by reaction of the correspondent oxazolidine with a complex alkyllithium derivatives and was the intermediate for the synthesis of... 

Oxidation of oxazolidine derivatives (275) gives isomeric pairs (A) and (B) of a-methoxy-substituted oxazolidine nitroxyl radicals (276a-d, f, g) and a,a-dimethoxy-substituted nitroxyl radical (276e) (Scheme 2.102) (515). 

Narasaka et al.16 reported that 53 catalyzes Diels-Alder reactions of 54-type substrates with diene in the presence of 4 A molecular sieves (Scheme 5-18). A remarkable solvent effect on the enantioselectivity is observed. High enantio-selectivity is attained using mesitylene as the solvent. As shown in Scheme 5-18, the reaction of 54a with isoprene proceeds smoothly in this solvent, affording product 55a with 92% ee. Other 3-(3-substituted acryloyl)-l,3-oxazolidin-2-ones 54b-d also give good results (75-91% ee) when reacted with cyclopentadiene. 

Formation of enantio- and diastereoenriched l-aza-4-oxa-7-thiabicyclo[3.3.0]octan-8-ones 453a and 453b was accomplished by ring closure of acyl-substituted. Y-bcnzyl thiocarbamates 452 in presence of Amberlyst 15 and 1,3-propanedithiol via a rearrangement of the oxazolidine ring (Equation 213) <2000JPR828>. 

Finally, intramolecular Michael addition from a 3-(2-oxo-but-3-enyl)-oxazolidin-5-one was reported to be catalyzed by boron trifluoride and afforded the cyclized product in fair yields. However, substitution at the enone group resulted in a less efficient cyclization <1996TL14757>. 

Perhydrooxazolo[3,2- ]pyridines 338 are excellent precursors of iminium ions 339 obtained after treatment of the oxazolidine with either a Bronsted or Lewis acid. Trapping of these intermediate iminium ions with nucleophiles then allows for substitution at the C-8a position together with ring opening, yielding functionalized piperidines 340 (Scheme 93). 

Starting from levulinic acid, it was possible to obtain 8a-substituted-4-phenyltetrahydro-l//-pyrrolo[2,l-c][l,4]oxa-zinc-1. />(7//)-dioncs 170 (Scheme 26) via Strecker reaction. Compound 171 was treated with 1 equiv of sodium hydroxide and the salt reacted with (f )-phenylglycinol to give a mixture of the Schiffs base 172 and the 1,3-oxazolidine 173 that was reacted with trimethylsilyl cyanide. Further treatment with HCl-saturated methanol afforded a mixture of 174 and 175. Heating at 200 °C in a sealed tube provided 170 as two separable isomers in 73% and 10% yields, respectively <1999TL5753>. 

Corey and colleagues215 prepared chiral aluminum complexes from chiral bis(sulfona-mides) and trimethylaluminum. These were successfully applied in the cycloadditions of 3-acryloyl-l,3-oxazolidin-2-one (17a) with substituted cyclopentadienes. Thus, the reaction of 3-acryloyl-l,3-oxazolidin-2-one with 5-(benzyloxymethyl)cyclopentadiene (331) afforded 332 with 94% ee (equation 93). A transition state was proposed based on the X-ray structure of the chiral catalyst and on NMR data of the 1 1 complex between 333... 

Afterwards, the authors found that catalyst 426 with SbFf, as the counterion demonstrated higher inductions in the reactions of substituted iV-acryloyI-1,3-oxazolidin-2-oncs... 

Davies and colleagues266 studied the use of copper(II) complexes of chiral bis(oxazoli-dine) 430 as catalysts in the cycloadditions of cyclopentadiene to substituted /V-acryloyl-l,3-oxazolidin-2-ones. They observed high endo and enantioselectivities. Again, the highest enantioselectivities were observed using SbEfi as the counterion, although differences were small this time ee values of 92 and 95% were obtained for the triflate and S h I Y> based catalysts, respectively. 

Several chiral lanthanide(III) Lewis acid catalysts, derived from chiral binaphthols, have been used in the cycloaddition reactions of cyclopentadiene with substituted iV-acryloyl-1,3-oxazolidin-2-ones. A catalyst derived from ytterbium triflate, (R)-binaphthol... 

Bromoethylamine (11.133, R = Br, Fig. 11.18) is a potent nephrotoxin used to create an experimental model of nephropathy. Its mechanism of toxicity is postulated to involve perturbation of mitochondrial function, and its metabolism was investigated in a search for toxic metabolites. In rat plasma, 2-bromoethylamine was converted to aziridine (11.134), formed by intramolecular nucleophilic substitution and bromide elimination [155], Another major metabolite was oxazolidin-2-one (11.136). This peculiar metabolite resulted from the reaction of 2-bromoethylamine with endogenous carbonate to form carbamic acid 11.135, followed by cyclization-elimination to oxazoli-din-2-one. In aqueous media containing excess carbonate, the formation of... 

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-... 

One of the best examples of the utility of enzymatic synthesis in catalyzing reactions that cannot be accomplished by any other route is the synthesis of substituted oxazolidine diesters. The oxazolidine ring is extremely water sensitive, the oxazolidine rapidly reverting back to the alkanolamine and aldehyde in the presence of water. Bis-oxazolidines have been used as hardeners for polymer coatings but the diester based on the hydroxyethyl oxazolidine and adipic acid cannot be synthesized directly with chemical catalysis because of the rapid rate of reaction of the oxazolidine ring with either the water from the esterification or the alcohol from transesterification. ... 

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