Oxazolidine diastereoselective alkylation

SCHEME 2.50 Diastereoselective alkylation of iV-acyl oxazolidines by Brigaut. 

In the course of examining the chemistry of oxazolidines, Meyers developed diastereoselective alkylation reactions of fused, bicyclic lactams such as 91 (Scheme 3.15). The approach is particularly useful for the construction of a large array of molecules containing quaternary stereogenic centers [68]. The starting bicyclic lactams are readily prepared by condensation of chiral /3-amino alcohols such as 89 with keto acids 90 to give 91, which subsequently participates in diastereoselective alkylation reactions. Hydrolysis... 

Diastereoselective a-alkylation of a-amino acids.1 This reaction is based on the observation that 2-(/-butyl)-N-benzoy I-1,3-oxazolidines (1) are alkylated with high stereoselectivity from the side opposite to that of the /-butyl group. These... 

Using the same principle as that described for l,3-dioxolan-4-ones, it is possible to a-alkylate 2-amino acids without racemization76,78. An A. O-acetal is formed from an (7 )-amino acid 1, e.g., with trimethylacetaldehyde (R2 = -Bu) the l,3-oxazolidin-5-ones 2 and 3 are furnished with a defined diastereoselectivity, which is the first stage in the process of self-reproduction of chirality 82. Formation of the enolate 4 from 2 and attack of an electrophile in the second step gives the product 6 with retention of configuration in the a-position, and 7 with inversion of configuration, again with a defined diastereoselectivity. Hydrolysis yields the a-alkylated amino acids 10 and 11. 

The diastereoselectivity is reversed in the alkylation of the enolate derived from the structurally very similar bicyclic lactam, tetrahydro-3-phenyl-l//.577-pyrrolof 1,2-c]oxazol-5-one (3). Thus, the major diastereomer 4 produced has the tram relationship between the newly introduced substituent in the pyrrolidine ring and the fused oxazolidine ring residue11,12. Only active electrophiles such as iodomethane, 3-halopropenes or (halomethyl)benzenes react11,12. Base-catalyzed equilibration of the product obtained by reaction with 3-bromocyclohexene gives a 50 50 mixture of the cis- and rra s-diastereomers11. 

Acyl-l,3-oxazolidine-2-thiones, chiral (1). Nagao and co-workers1 have prepared the chiral 3-acetyl-l,3-oxazolidine-2-thiones (la and lb) and used them to effect diastereoselective aldol reactions. The two chiral auxiliaries show, as expected, opposite diastereoselectivities, but contrast with the diastereoselectivities observed with chiral 4-alkyl-2-oxazolidones (11, 379-381). This aldol reaction has been used to prepare the chiral azetidinone 4 (equation I) and (-I- )-Prelog-Djerassi lactone. 

Diastereoselective Cy clopropanation and Alkylation of Chiral Oxazolidines Derived from Ephedrine. Ephedrine forms... 

Reductive lithiation of a diastereoisomeric mixture (dr 92 8) of the bicyclic 2-phenyl-l,3-oxazolidine 189 followed by alkylation allowed the highly diastereoselective synthesis of N-(a-alkyl-substituted)benzyl-2-hydroxymethylpiperidines 190 and 191 <01TL129>. 

Both cis (10) and irons diastereoisomers of aryl and alkyl chiral oxazolidine sulfonium salts derived from (-)-(/ )-2-phenylglycinol have been demonstrated to be good to excellent chiral auxiliaries for the diastereoselective synthesis of (2/ ,35)-tra j -epoxyamides (11, Scheme A) The diastereoselective outcome depends on the stereochemistry of the chiral centre at the C(4) position of the oxazole moiety (<98% de with R configuration). 

A two-step approach for the diastereoselective synthesis of 4-carboxymethyl-3-alkyl (aryl)oxazolidin-2-ones (391) which proceeds via the intermediate formation of carboxy-methyl-3-alkyl(aryl)-tV-r-butoxycarbonylaziridines (390), has been described " see... 

Figure 11.37 Diastereoselective a-alkylation of a (S)-4-benzyl-3-[ t- C ]acyl- 1,3-oxazolidin-2-one using an unlabeled primary alkylating agent...

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