Cyclic derivatives, diastereoselective asymmetric

Bode and co-workers have extended the synthetic ntility of homoenolates to the formation of enantiomerically enriched IV-protected y-butyrolactams 169 from saccharin-derived cyclic sulfonylimines 167. While racemic products have been prepared from a range of P-alkyl and P-aryl substitnted enals and substitnted imi-nes, only a single example of an asymmetric variant has been shown, affording the lactam prodnct 169 with good levels of enantioselectivity and diastereoselectivity (Scheme 12.36) [71], As noted in the racemic series (see Section 12.2.2), two mechanisms have been proposed for this type of transformation, either by addition of a homoenolate to the imine or via an ene-type mechanism. 

The new heterocyclic derivative 130 has been shown to be an efficient chiral auxilliary for asymmetric desymmetrization of cyclic meso-l,2-diols via diastereoselective acetal cleavage . 

Asymmetric Diels-Alder reactions. Unlike methyl crotonate, which is a weak dienophile, chiral (E)-crotonyl oxazolidinones when activated by a dialkylaluminum chloride (1 equiv.) are highly reactive and diastereoselective dienophiles. For this purpose, the unsaturated imides formed from oxazolidinones (Xp) derived from (S)-phenylalanol show consistently higher diastereoselectivity than those derived from (S)-valinol or (IS, 2R)-norephedrine. The effect of the phenyl group is attributed in part at least to an electronic interaction of the aromatic ring. The reactions of the unsaturated imide 1 shown in equation (I) are typical of reactions of unsaturated N-acyloxazolidinones with cyclic and acyclic dienes. All the Diels-Alder reactions show almost complete endo-selectivity and high diastereoselectivity. Oxazolidinones are useful chiral auxiliaries for intramolecular Diels-Alder... 

A highly selective method for the preparation of optically active 3-substituted or 3, y-disubstituted-S-keto esters and related compounds is based on asymmetric Michael additions of chiral hydrazones (156), derived from (5)-l-amino-2-methoxymethylpyrrolidine (SAMP) or its enantiomer (RAMP), to unsaturated esters (154).167-172 Overall, a carbonyl compound (153) is converted to the Michael adduct (155) as outlined in Scheme 55. The actual asymmetric 1,4-addition of the lithiated hydrazone affords the adduct (157) with virtually complete diastereoselection in a variety of cases (Table 3). Some of the products were used for the synthesis of pheromones,169 others were converted to 8-lactones.170 The Michael acceptor (158) also reacts selectively with SAMP hydrazones.171 Tetrahydroquinolindiones of type (159) are prepared from cyclic 1,3-diketones via SAMP derivatives like (160), as indicated in Scheme 56.172... 

Py used a nitrone-alkene coupling in a short, asymmetric synthesis of (+ )-hyacinthacine A2 (Scheme 5.43).74 The key carbon-carbon bond-forming step in their approach involved the highly diastereoselective reductive coupling of the L-xylose-derived cyclic nitrone 66 to ethyl acrylate.74... 

A number of acylnitroso compounds derived from (/ )-mandelic acid or its analogs react in the cycloaddition with cyclic dienes with moderate to high asymmetric induction. The reaction is performed in methanol by oxidizing the A-acylhydrcixylamines 1 in the presence of the diene the diastereoselectivity increases by lowering the temperature (Table 3)99,10°. 

Carbamoyl nitroso dienophiles, derived from chiral pyrrolidines, have been generated and their reactivity with cyclohexa-diene investigated. Using (—)-fra/w-2,5-dimethylpyirolidine as the auxiliary, the [4 + 2] cycloadduct is isolated in 82% yield and with 98% diastereomeric excess (eq 10). Similarly, chiral ynamine dienophiles have been utilized in asymmetric [4 + 2] cycloadditions with a,p-unsaturated nitroalkenes to afford cyclic nitronic esters. The resulting esters subsequently undergo a rapid [1,31-rearrangement to afford chiral cyclic nitrones in moderate yield and high diastereoselectivity (eq 11)-... 

The arylsulfonyl carbanion accelerated Claisen rearrangement is completely regioselective and has also been found to be highly diastereoselective (Scheme 2). The stereochemical course of the reaction conforms to the familiar chair-like transition state model usually invoked for the classic thermal process. Recently, high degrees of asymmetric induction have been observed in tlie rearrangements of chiral cyclic phosphoramidate stabilized carbanion derivatives. ... 

In spite of the high level of interest in the asymmetric synthesis of a-amino phosphonic acids, less is known in the case of cyclic a-amino phosphonates. Although in recent years descriptions of promising pharmaceutical applications for cyclic compounds (and acylated derivatives thereof) have been published [61-64], until now no efficient general asymmetric route has been available to prepare this class of a-amino phosphonates. Several attempts at a diastereose-lective synthetic route which were made by the addition of a stoichiometric amount of chiral phosphites to cyclic imines, namely thiazolines, gave only limited diastereoselection ratios of dr=2 1 or below [75,76]. 

The use of the carbanion derived from the chloroallylphosphonate (163) in the enantioselective synthesis of cyclopropanes (164) by Michael addition to a,P-unsaturated ketones has been the subject of a short review (Scheme 18). Denmark s group have published full details of the asymmetric Michael addition reactions of cyclic enones with carbanions derived from l,3,2-oxa2aphosphor-inane 2-oxides (165) and (167). y-Addition to give (166) predominates although the extent of this depends on the ring size of the Michael acceptor. The level of diastereoselectivity depends on the stereochemistry of the allylphosphonate used ... 

Asymmetric Diels-Alder reactions of the chiral dienophile 5-(alkyloxy)-5 /-2-furanone (D), derived fi om the chiral auxiliary 10, with a variety of dienes have been studied in toluene at 120°C. Thereby, diastereoselectivities up to 96% de were determined. From cyclic dienes with exocyclic or vinylic double bonds, such as (3), substituted decalins were obtained as optically pure cycloadducts. 

Acetal Fission in Desymmetrization of 1,2-Diols. The asymmetric desymmetrization of cyclic i eso-l,2-diols was accomplished via diastereoselective acetal fission. After acetalization of ffiei >-l,2-diols with the C2-symmetric bis-sutfoxide ketone, the resulting acetal was subjected to base-promoted acetal fission, followed by acetylation or benzylation to give the desymmetrized diol derivatives. Interestingly, the counter-cation of the base had a remarkable effect on the diastereoselectivity of the reaction. While LHMDS produce the desired compound with low diastereoselectivity, 90% and >96% diastereomeric excesses were obtained... 

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