Synthesis of -a-substituted

Darzens reaction can be used to efficiently complete the stereoselective synthesis of a"-substituted epoxy ketones. As an example, Enders and Hett reported a technique for the asymmetric synthesis of a"-silylated a,P-epoxy ketones. Thus, optically active a -silyl a-bromoketone 38 was treated with LDA followed by the addition of benzaldehyde to give a"-silyl epoxyketone 40 in 66% yield with good... 

The reaction of ozone with an aromatic compound is considerably slower than the reaction with an alkene. Complete ozonolysis of one mole of benzene with workup under non-oxidative conditions will yield three moles of glyoxal. The selective ozonolysis of particular bonds in appropriate aromatic compounds is used in organic synthesis, for example in the synthesis of a substituted biphenyl 8 from phenanthrene 7 ... 

Enamines 1 are useful intermediates in organic synthesis. Their use for the synthesis of a-substituted aldehydes or ketones 3 by reaction with an electrophilic reactant—e.g. an alkyl halide 2, an acyl halide or an acceptor-substituted alkene—is named after Gilbert Stork. 

The Stork enamine reaction is an important and versatile method for the synthesis of a-substituted aldehydes and ketones. Such products should in principle also be... 

Conceptually related methods have been employed in the synthesis of a-substituted allylboron reagents 85 and 106. In the case of 8, a benzimidazoleoxy leaving group is introduced as part of the a-alkoxy-2-butenyllithium reagent. Fragmentation of the ate complex must be conducted at — 100 °C in order to avoid the isomerization of 8, which occurs readily if 8 is allowed to warm to — 78 °C for one hour before addition of an aldehyde5. 

Microwave-Assisted Synthesis of a Substituted Pyran Using Ionic Liquid Tagging... 

The synthesis of a-substituted phosphonates 89, via the electrophilic addition of phosphorylated C-radicals 88 (generated by reaction of BujSnH to the readily accessible a-phosphoryl sulfides (or selenides)) and electrophilic addition to electron rich alkenes, has been described [57] (Scheme 26). A large excess of alkene is necessary to minimize the competitive formation of the undesired compound 90 resulting from direct reduction of the initial radical 88. The ratio 89/90 has been measured for each example. The synthesis of the a-mono- or a,a-di-substituted (R or phosphonates 89 shows that the free radical approach... 

Very simple synthesis of a-substituted y-methyl-y-lactones is also possible by olefination using nitroalkanes followed by reduction, as shown in Eq. 7.128.174... 

Enantioselective synthesis of /1-amino acids is important as they are present in various natural products and in many biologically active compounds [26,27]. Several methods exist for the enantioselective synthesis of -substituted /1-amino acids (/l3-amino acids) however, synthesis of a-substituted /1-amino acids (/l2-amino acids) is very limited [28,29]. A report on highly enantioselective hydrogen atom transfer reactions to synthesize /l2-amino acids (Scheme 9) has recently been described [30]. 

A synthesis of A-substituted a-aminobenzylphosphinic acids starts from ammonium hypophosphite this is allowed to react with primary amines together with aldehydes or ketones in the presence of HC1.60 The nature of the products and general success of the Atherton-Todd reaction for the preparation of dialkyl- and diaryl-phosphinic amides from secondary phosphine oxides depends on the order in which reactants are mixed and on the choice of polyhalogen reactant.61... 

The synthesis of a substituted derivative of 2-keto-l,2,3,4-tetrahydro-dibenzothiophene is discussed in Section VI, D. 

Despite the typical use of the 1,5-dienic system in the hetero-Cope rearrangement the participation of triple bonds, C=N and C=C, in the [3,3]-sigmatropic rearrangement was also reported. Synthesis of A-substituted benzimidazolinones 175 by a hetero-Cope rearrangement of the adduct 174 formed by reaction of A-arylhydroxamic acids 172 with cyanogen bromide 173 in the presence of triethylamine and at low temperatures was reported by Almeida, Lobo and Prabhakar (equation 51). 

The potential of this catalytic approach is further demonstrated by the synthesis of a substituted 1,3-oxazinan-2-one via a reduction-cyclization strategy (Scheme 8). 

A new protocol was developed for the synthesis of A-substituted thioamides, employing arenes and isothiocyanates in 1-butyl-3-methylimidazolium chloro-aluminate IL, [bmim][AlCl4], as a homogenous Lewis acid catalyst and solvent,Scheme 12. 

Scheme 18 Synthesis of a Substituted Lanthionine by Nucleophilic Substitution of Trt-Protected 3-Iodoala-nine[401...

Therefore, in principal, condensation of a primary amine with an enantiomerically pure ketone should allow asymmetric synthesis of a-substituted primary amines. This approach has been applied to the synthesis of a-amino acids, for example, using the imine prepared from a-amino esters and (l.S, 2,S ,5,S )-2-hydroxy-3-pinanone, via an amino-substituted ester enolate anion with some success39 40. Application of this approach to simple primary amines has seldom been reported. 

After the successful asymmetric synthesis of a-substituted P-amino ketones (R)-14, we envisaged the diastereo- and enantioselective synthesis of a,P-disubstituted Mannich bases. As shown in Scheme 1.1.4, we were able to use benzaldehyde-N-phenylimine [11] as well as a-alkoxycarbonylaminosulfones [12] as Mannich electrophiles to synthesize in good overall yields and high de- and ee-values the anti-configured P-amino ketones (R,S)-15 and (R,S)-16, respectively [13]. 

Davis et al. [88] described the asymmetric synthesis of a-substituted primary sulfonamides involving the diastereoselective a-alkylation of N-sulfonylcamphor-imine dianions, while Huart and Ghosez reported an enantioselective synthesis of bicyclic cyclopentenones via a stereoselective 1,4-addition of metallated enan-tiopure sulfonamides to cyclic enones [89]. 

TABLE 16. Synthesis of a-substituted ketones (208) from p-anisaldehyde, 1-chlorobutyl p-tolyl sulfoxide and electrophiles... 

Scheme 17 Synthesis of a Substituted Phenylglycine via the Chiral Strecker Reaction ...

Scheme 21 Asymmetric Synthesis of a /-Substituted Glutamic Acid from Pyroglutamic Acid[951...

An elaborate synthesis of a substituted anisole was followed by ether cleavage, cycliz-ation and dehydration to the chromene (179 Scheme 30) (54JA5439). 

Conjugate addition-aldol reactions. A novel synthesis of a-substituted a,(3-enones involves conjugate addition of 1 to an a,p-enone the resulting 0-phenyl-selenoboron enolate undergoes aldol condensation with aldehydes. The adduct on oxidative elimination furnishes unsaturated p-hydroxy ketones.1 Example ... 

The application of this reaction to other ring systems has shown that the yield of the bicyclic hydrocarbon decreases as the strain involved in the product increases. For example, the mercury sensitized decomposition of bicyclo [3.2.0] heptanone-3 (XXIII) leads to very little of bicyclo [2.2.0] hexane and gives more of bicyclo [2.1.1] hexane than of bicyclo [2.2.0] hexane. The reaction has been successfully applied to the synthesis of a substituted bicyclo [2.1.0] pentane (XXVIII) from a sub-... 

Synthesis of a-substituted and a, /i-disubstitutcd amines with high stereoselectivity has been achieved by addition of alkyllithiums to chiral hydrazones.50... 

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