A-Acyloxazolidin-2-ones

The Reformatsky reaction with A(-acyloxazolidin-2-ones and -thiazolidin-2-thiones provides a route to /3-keto esters. The electrolysis of a-bromoalkanoic esters in acetonitrile on a zinc anode with ZnBr2 and Bu NBEi as supporting electrolytes gives acetoacetic ester derivatives. The acetonitrile solvent is partially consumed. 

Alkylations. The use of LDA as a base in alkylations is almost universal. Listed here are some new examples perfluoroalkylation of A-acyloxazolidin-2-ones, alkylation of 2-cyanocycloalkanones via the SAMP derivatives, and alkylation of a-(p-toluenesulfinyl)alkanoic esters. The last of these reacts with A-tosylimines to generate adducts that are precursors of (i-amino esters. 

In a preliminary report, Chen and co-workers [30] obtained moderate enantioselectivity in the addition of thiophenol to acyclic benzimides, catalyzed by 11 (55-75% ee). The Deng group [35] successfully exploited a,(3-unsaturated A-acyloxazolidin-2-ones as acceptors. After a careful screening of bifunctional cinchona alkaloid derivatives, they identified the novel thiourea 14 as the most... 

An efficient sulfa-Michael-aldol tandem reaction between 2-mercaptobenzalde-hydes and a,(3-unsaturated A-acyloxazolidin-2-ones catalyzed by thiourea 12 was disclosed by Wang and co-workers [36]. The resulting benzothiopyrans, containing three stereogenic centers, were obtained with high enantio- and diastereoselectivities regardless of the electronic and steric nature of the (3-substituent on the Michael acceptor (Scheme 14.8). 

Although the racemization of the a-carbon can now be considered a potential problem, the synthesis of 32-peptides has been achieved in the same way as seen for 33-peptides. As the 32-amino acids cannot be prepared from the analogous a-amino acids, Seebach and co-workers 5,7 opted to use Evans oxazolidinone chemistry to produce enantiomerically pure 32-amino acids. Alkylation of 3-acyloxazolidin-2-ones 17 with A-(chloromethyl)benzamide yielded the products 18 with diastereomeric ratios between 93 7 and 99 1 (Scheme 8). Removal of the chiral auxiliary (Li0H/H202) and debenzoylation (refluxing acid) was followed by ion-exchange chromatography to yield the free 32-amino acids 20 which were converted by standard means into Boc 21 or benzyl ester 22 derivatives for peptide synthesis. 

N-Acyloxazolidin-2-ones. A convenient A-acylation of heterocycles is performed by heating a carboxylic acid with PivCl and triethylamine in toluene. 

P-Amino acids. A method involving asymmetric alkylation of chiral N-acyloxazolidin-2-ones with t-butyl bromoacetate and saponification furnishes substituted succinic monoesters. On submission to degradation by (PhO)2PONj, properly protected P-amino acids are obtained. 

Michael reaction The conjugate addition of Ai-acyloxazolidin-2-ones to nitroalkenes is best promoted by a combination of TiCl4 and i-Pr2NEt. Excellent stereoselectivity is observed from reactions of substrates in which the heterocycle is substituted at C-4 with an isopropyl group (stereocontroller) and gew-dimethylated at C-5. 

SCHEME 14.7. Sulfa-Michael addition to a,p-imsaturated JV-acyloxazolidin-2-ones catalyzed by thiourea 14. 

The same reaction carried out in dioxane required relatively long irradiation times, and stops at the P-amino ester stage 29 Keto-esters result from sonication of 3-acyloxazolidin-2-ones with bromoesters and zincxhe reaction is relatively slow and reflux for several hours is required after sonication. Substrates with a chiral center next to the amide carbonyl group react with preservation of the configuration (Eq. 75). 

Asymmetric conjugate addition of O-benzylhydroxylamine to a,P-unsaturated 3-acyloxazolidin-2-ones was smoothly catalyzed by Sc(OTf)3-(Tr-pybox) complex in the presence of MS 4A to give the corresponding -amino carbonyl compounds in good conversions with good enantioselectivities [125]. The product (5) might be produced by amidolysis of (4) and/or the starting oxazolidinone with benzylhydroxylamine (Scheme 12.49). 

The first example of an enantioselective thiadiene cycloaddition involved the reaction of 2,-4-diphenyl- 1-thiabuta-1,3-diene with l-propenoyl-l,3-oxazolidin-2-one. Stoichiometric quantities of a copper triflate bis-imine complex catalyst 428 and 4 A molecular sieves are necessary to achieve the highest enantioselectivity and the best endojexo ratio. The absolute configuration of the major endo isomer was determined by reduction of the acyloxazolidine side chain to the known (3/ ,4/ )-5-hydroxymethyl derivative (Scheme 137) <1997J(P1)2957>. The process is improved using a homochiral Cu triflate or Ni perchlorate bis(oxazoline) complex when catalytic amounts are adequate for a range of thiabutadienes <1999CC1001>. 

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