Optically activ oxazolidine

Although the photodriven reactions of chromium carbene complexes with imines superficially resemble those of free ketenes, there are major differences. The optically active oxazolidine carbene (Table 5) gave excellent yields and high ee values when allowed to react with imidates, oxazines, thiazines, and... 

SCHEME 40. Diastereoselectivity in the chiral-auxihary-controlled singlet oxygen ene reaction of optically active oxazolidines... 

Arylsulfonyloxazolidines.1 The optically active oxazolidine 1, prepared from (R)-(N-toluenesulfonyl)phenylglycinol and 2-hydroxymethylenecyclohexanone,... 

Some evidence for the mechanism being reaction mode (a) comes from the conversion of optically active oxazolidine (42) to a racemic mixture of pyrrolidine Scheme 22), obviously via the achird intermediate (44), since in a pinacolic-type rearrangement via (45), the chiral information would have been... 

Fisher carbenes easily react with an amine to give the aminocarbene, and the aminocarbene reacts with carbon monoxide under light irradiation to give an aminoester as shown in eq. (13.47) [79]. If the optically active oxazolidine derivatives are used as the aminocarbene, by photolytic carbonylation the above synthesis of amino acid ester gives an optically active derivative as shown in eq. (13.48) [79]. 

Photodriven reactions of Fischer carbenes with alcohols produces esters, the expected product from nucleophilic addition to ketenes. Hydroxycarbene complexes, generated in situ by protonation of the corresponding ate complex, produced a-hydroxyesters in modest yield (Table 15) [103]. Ketals,presumably formed by thermal decomposition of the carbenes, were major by-products. The discovery that amides were readily converted to aminocarbene complexes [104] resulted in an efficient approach to a-amino acids by photodriven reaction of these aminocarbenes with alcohols (Table 16) [105,106]. a-Alkylation of the (methyl)(dibenzylamino)carbene complex followed by photolysis produced a range of racemic alanine derivatives (Eq. 26). With chiral oxazolidine carbene complexes optically active amino acid derivatives were available (Eq. 27). Since both enantiomers of the optically active chromium aminocarbene are equally available, both the natural S and unnatural R amino acid derivatives are equally... 

Development of new synthetic routes to optically active (3-lactam derivatives is still an attractive problem in organic chemistry. As a synthetic approach to penicillin derivatives, photocyclization of oe-oxoamides 76 to (3-lactams has long been studied 41, 42). This reaction (Scheme 6), however, results in a complex mixture of racemic cis-and trans-isomers of (3-lactams 72 and of oxazolidin-4-ones 73, since the reaction proceeds via a zwitterionic intermediate 7143>. Of these isomers, only the optically... 

Chiral oxazolidine compounds have also been used as chiral auxiliaries for asymmetric Diels-Alder reactions. Adam et al.8 demonstrated the cycloaddition of optically active 2,3-dimethyl oxazolidine derivatives with singlet oxygen. As shown in Scheme 5-9, the reaction of chiral substrate 39 with singlet oxygen provides product 40 in high diastereomeric ratio. 

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. 

Similarly, photolysis of chromium complex (CO)5Cr=C(OMe)(c-Pr) in the presence of two equivalents of the optically active 3-ethenyl-6(S)-phenyl-2-oxazolidinone under 90 psi CO pressure produced in high regio- and diastereo-selectively the 3-oxazolidine-substitued (2i ,3S)-cyclobutanone, in optical purity of > 97% de (equation 75)148. 

Analogous to the use of chiral acetals one can employ chiral N,O-acetals, accessible from a, -unsatu-rated aldehydes and certain chiral amino alcohols, to prepare optically active -substituted aldehydes via subsequent Sn2 addition and hydrolysis. However, the situation is more complicated in this case, since the N,0-acetal center constitutes a new stereogenic center which has to be selectively established. The addition of organocopper compounds to a, -ethylenic oxazolidine derivatives prepared from unsaturated aldehydes and ephedrine was studied.70-78 The (diastereo) selectivities were rather low (<50% ee after hydrolysis) in most cases, the highest value being 80% ee in a single case.73 There is a strong solvent effect in these reactions, e.g. in the addition of lithium dimethylcuprate to the ( )-cinnamaldehyde-derived oxazolidine (70 Scheme 28) 73 the (fl)-aldehyde (71) is formed preferentially in polar solvents, while the (S)-enantiomer [ent-71) is the major product in nonpolar solvents like hexane. This approach was utilized in the preparation of citronellal (80% ee) from crotonaldehyde (40% overall yield).78... 

The six optically active alkaloids ephedrine, pseudoephedrine, norephedrine, norpseudoephedrine, and the N-methylated N-methylephedrine and N-methylpseudoephedrine are described in detail in Reti s review (2). Two new alkaloids of related structure have since been identified in Ephedra species, namely, (9-benzoylpseudoephedrine (271) and the oxazolidine derivative ephe-droxane (272). The 4-quinolone derivative ephedralone, recently isolated from Ephedra alata (273), may be of similar biogenetic origin as the ephedrines. Ephedra species also contain macrocyclic alkaloids of more complex structure (275). The two major Ephedra alkaloids (—)-ephedrine and (+)-pseudoephedrine are diastereomers. (—)-Ephedrine has the erythro and (+)-pseudoephedrine has the threo configuration. 

Oxazolidine-2,5-diones (276) are the anhydrides of iV-carboxy-a-amino acids. They react with nucleophiles, such as water, alcohols or amines, to give unstable N-carboxy acids, esters or amides which lose carbon dioxide (equation 87). The products (277) are themselves nucleophilic reagents and may react with another molecule of the oxazolidinedione to yield a dipeptide (equation 88). The process may continue, leading to a polypeptide. Chiral oxazolidine-2,5-diones derived from optically active a-amino acids undergo stereospecific polymerization (72C501). 

Aldol reactions of methyl ketones. The optically active 1,3-oxazolidine (1) formed from a methyl ketone and ( — (-norephedrine aftir conversion to the tin(ll) enolate undergoes enantioselective aldol condensation with aldehydes. The enantioselectivity is partic-... 

Syntheses of optically active silicon-containing amino acids, particularly, of sila-proline-, imidazolidine-, and oxazolidine-based amino acids 03MI86. 

With optically active amino alcohols and aldehydes, a mixture of diastereomers generally results. For N—H oxazolidines, the ratio of isomers is about 2 1, and for N—Me or N—Pr analogues the ratio is about 9 1. For A-tosyl derivatives, however, diastereomerically pure 2,4-cw-oxazolidines are isolated <92H(33)28i>. Trans isomers (189) are obtained in ratios >10 1 from the zinc chloride or trimethylsilyl triflate-catalyzed reaction of 2-methoxy-oxazolidines with allyltrimethylsilane or... 

Optically active 3-lactones are readih p using 72 as the chirality inducer. - - The p acids. The [2 -f 2]cycloaddition of ketenes ai nine leads to numerous c y-2,3-disubstituted f Reports on the advances of asymmetric 1 of diazoalkanes to A-(2-alkenoyl)oxazolidin-. 73, showing cooperative chiral control by the ral ligand.An intramolecular cycloaddition a chiral cyclic A,N -dimethylaminal unit ad>i 74) proves very successful in the asymmetric nitrone lacks stereoselectivity, - ... 

An access to optically active ral oxazolidin-2-ones to react w of a-haloketones with acyl cyan Dimerization of enones is to hydroxy ketone is formed by a r chain. The net result is that of an... 

An access to optically active P-hydroxy acids uses the bromoacetyl derivatives of chiral oxazolidin-2-ones to react with aldehydes. " 1,3-Diketones are obtained from reaction of a-haloketones with acyl cyanides. ... 

Dienophiles prepared from a,B-unsaturated acids and 1,3-oxazolidin-2-one react with cyclopentadiene in the presence of catalytic amounts of a chiral alkoxytitanium(IV) complex and molecular sieves to give optically active adducts (Scheme 52) via Carbonylation Reactions. - The temporary incorporation of a co-ordinating phosphine into a tetracyclic phyllanthocin precursor... 

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