Ketones, asymmetric alkylation condensation

Asymmetric alkylation andaldol condensations.2 The enolate (2) of 1 reacts with primary iodides to give essentially a single product (3), in which the alkyl group is syn to the cyclopentadieny ring. Aldol condensation with acetone leads to only one observable product (4). Only two isomeric products are obtained on aldol condensation with prochiral aldehydes and ketones as expected for a rranx-enolate, the i/ww-aldol predominates or is the exclusive product (5) as in the case of pivaldehyde. 

Another route to (+)-19-nortestosterone (73) started firom 2-methyl-l,3 cyclopentanedione (74). The asymmetric aldol condensation of the Michael adduct using L-phenylalanine produced the opticaUy active enone (75). The PdCh-catalyzed oxidation yielded crystalline trione (76) in 77% ee, which was recrystallized as an optically pure form. Reduction of the double bond and aldol condensation afforded the desired cd tratu-fused ketone (77). The construction of the A-ring was carried out by alkylation with... 

Enolboration of Ketones and Opening of meso-Epoxides. Methyl alkyl ketones have been successfully enolized by IpciBX (X = OTf or Cl) in the presence of a tertiary amine. The corresponding enolborinates have been used in asymmetric aldol condensations (eq 5). The reagent has also been applied to the enantioselective opening of mcj o-epoxides to form the corresponding nonracemic chlorohydrins (eq 6). ... 

Chiral Auxiliary for Asymmetric Induction. Numerous derivatives of (—)-8-phenylmenthol have been utilized for asymmetric induction studies. These include inter- and intramolecular Diels-Alder reactions, dihydroxylations, and intramolecular ene reactions of a,p-unsaturated 8-phenylmenthol esters. These reactions usually proceed in moderate to good yield with high diastereofacial selectivity. a-Keto esters of 8-phenylmenthol (see 8-Phenylmenthyl Pyruvate) have been used for asymmetric addition to the keto group, as well as for asymmetric [2 -F 2] photoadditions and nucleophilic alkylation. Ene reactions of a-imino esters of 8-phenylmenthol with alkenes provide a direct route to a-amino acids of high optical purity. Vinyl and butadienyl ethers of 8-phenylmenthol have been prepared and the diastereofacial selectivity of nitrone and Diels-Alder cycloadditions, respectively, have been evaluated. a-Anions of 8-phenylmenthol esters also show significant diastereofacial selectivity in aldol condensations and enantiose-lective alkene formation by reaction of achiral ketones with 8-phenylmenthyl phosphonoacetate gives de up to 90%. ... 

Stereoselective reduction of a-alkyl-3-keto acid derivatives represents an attractive alternative to stereoselective aldol condensation. Complementary methods for pr uction of either diastereoisomer of a-alkyl-3-hydroxy amides from the corresponding a-alkyl-3-keto amides (53) have been developed. Zinc borohydride in ether at -78 C gave the syn isomer (54) with excellent selectivity ( 7 3) in high yield via a chelated transition state. A Felkin transition state with the amide in the perpendicular position accounted for reduction with potassium triethylborohydride in ether at 0 C to give the stereochemi-cally pure anti diastereoisomer (55). The combination of these methods with asymmetric acylation provided an effective solution to the asymmetric aldol problem (Scheme 6). In contrast, the reduction of a-methyl-3-keto esters with zinc borohydride was highly syn selective when the ketone was aromatic or a,3-unsaturated, but less reliable in aliphatic cases. Hydrosilylation also provided complete dia-stereocontrol (Scheme 7). The fluoride-mediated reaction was anti selective ( 8 2) while reduction in trifluoroacetic acid favored production of the syn isomer (>98 2). No loss of optical purity was observed under these mild conditions. 

These bulky aluminium aryloxides will also promote a variety of carbon-carbon bond forming reactions with a high degree of regio and stereoselectivity. Examples include Michael addition to a,/S-unsaturated ketones, Diels-Alder additions, and Claisen rearrangements. In the case of Diels-Alder reaction, ATPH promoted the exo-selective condensation of a,/6-unsaturated ketones with dienophiles. The Claisen rearrangement can be catalysed by ATPH and its more Lewis acidic 4-bromo derivative. A series of chiral aluminium aryloxides were also synthesized and have been applied to asymmetric Claisen rearrangements, aldol reactions, and aldehyde alkylations. ... 

Further work on the preparation of chiral a-amino-acids reported in the past year (see also the section on asymmetric hydrogenation) includes an extension of the utility of anions derived from lactim ethers (228) in the synthesis of such compounds by condensations with aldehydes and ketones chiral inductions are somewhat lower than in the alkylations of (228) reported previously (4, 320). Enzyme-mediated hydrolysis of 5(4H)-oxazolones by chymotrypsin or subtilisin gives a-acylamino-acids with good enantiomeric enrichments, especially if the substrate carries bulky substituents. Schiff s bases of a-amino-esters can be enriched enantiomerically to an extent of up to 70% by sequential deprotonation with a chiral lithium amide and protonation with an optically pure tartaric acid. ... 

The ehiral phosphoiie aeid (i )-(231) has been shown as an efficient Bronsted aeid eatalyst in asymmetrie synthesis of various acyclic and endo exocyclic p-hydroxyenones (230) through a regiospecific aldol condensation between a,p- unsaturated ketones (228) and ethyl glyoxalate (229) (Seheme 60). Enantioseleetive synthesis of 3-indolyl-substituted isoindolin-l-ones (234) through the ehiral phosphoric add (235) catalysed asymmetric Friedel-Crafts alkylation of indoles (232) with 3-hydroxyisoindolin-l-ones (233) in excellent ehemieal yields (up to 99%) and with moderate to good enantioselectivities (up to 99% ee), has been described by Zhou et al. (Scheme 61). ... 

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