Preparation of optically active

Other uses of Snp2 are in the synthesis of fluorophosphate glasses having low melting temperatures (13—15), in formation of transparent film (16), and in the preparation of optically active alcohols (17). 

Pubhcations have described the use of HFPO to prepare acyl fluorides (53), fluoroketones (54), fluorinated heterocycles (55), as well as serving as a source of difluorocarbene for the synthesis of numerous cycHc and acycHc compounds (56). The isomerization of HFPO to hexafluoroacetone by hydrogen fluoride has been used as part of a one-pot synthesis of bisphenol AF (57). HFPO has been used as the starting material for the preparation of optically active perfluorinated acids (58). The nmr spectmm of HFPO is given in Reference 59. The molecular stmcture of HFPO has been deterrnined by gas-phase electron diffraction (13). 

Synthetic utility of stereoselective alkylations in natural product chemistry is exemplified by the preparation of optically active 2-arylglycine esters (38). Chirally specific a-amino acids with methoxyaryl groups attached to the a-carbon were prepared by reaction of the dimethyl ether of a chiral bis-lactam derivative with methoxy arenes. Using SnCl as the Lewis acid, enantioselectivities ranging from 65 to 95% were obtained. 

Lipase-catalyzed kinetic resolutions are often practical for the preparation of optically active pharmaceuticals (61). For example, suprofen [40828-46-4] (45), which is a nonsteroidal antiinflamatory dmg, can be resolved by Candida glindracea]i 2Lse in >95% ee at 49% conversion (61). Moreover, hpase-based processes for the resolution of naproxen [22204-53-1] and ibuprofen [15687-27-1] (61) have also been developed. 

NMR investigations in the diaziridine field also led to the problem of inversion stability at nitrogen. Further investigations paralleled those of oxaziridines NMR investigation in solution (67CB1178) was followed by preparative separation of invertomers and finally preparation of optically active individuals. 

The catalytic enantioselective cycloaddition reaction of carbonyl compounds with conjugated dienes has been in intensive development in recent years with the main focus on synthetic aspects the number of mechanistic studies has been limited. This chapter will focus on the development and understanding of cycloaddition reactions of carbonyl compounds with chiral Lewis acid catalysts for the preparation of optically active six-membered ring systems. 

Over the last few years severid examples have been reported in the field of asymmetric catidysis that are based on the interaction of two centers. Recently, Shibasaki and co workers have developed an asymmetric two-center catidyst. Scheme 3.14 shows preparation of optically active l.a binaphthol fBIN01.. This catidyst is effective in inducing the asymmetric uitto-iddol reacdon, as shovmin Scheme 3.15. 

Reductive alkylation with chiral substrates may afford new chiral centers. The reaction has been of interest for the preparation of optically active amino acids where the chirality of the amine function is induced in the prochiral carbonyl moiety 34,35). The degree of induced asymmetry is influenced by substrate, solvent, and temperature 26,27,28,29,48,51,65). Asymmetry also has been obtained by reduction of prochiral imines, using a chiral catalyst 44). Prediction of the major configurational isomer arising from a reductive alkylation can be made usually by the assumption that amine formation comes via an imine, not the hydroxyamino addition compound, and that the catalyst approaches the least hindered side (57). 

The synthesis of the trisubstituted cyclohexane sector 160 commences with the preparation of optically active (/ )-2-cyclohexen-l-ol (199) (see Scheme 49). To accomplish this objective, the decision was made to utilize the powerful catalytic asymmetric reduction process developed by Corey and his colleagues at Harvard.83 Treatment of 2-bromocyclohexenone (196) with BH3 SMe2 in the presence of 5 mol % of oxazaborolidine 197 provides enantiomeri-cally enriched allylic alcohol 198 (99% yield, 96% ee). Reductive cleavage of the C-Br bond in 198 with lithium metal in terf-butyl alcohol and THF then provides optically active (/ )-2-cyclo-hexen-l-ol (199). When the latter substance is treated with wCPBA, a hydroxyl-directed Henbest epoxidation84 takes place to give an epoxy alcohol which can subsequently be protected in the form of a benzyl ether (see 175) under standard conditions. 

Figure A8.3 Preparation of optically active a-amino acids via bioconversion of the corresponding a-aminonitriles.

Figure A8.9 Procedure for the preparation of optically active a-disubstituted amino acids through stereoselective enzymatic cydisation of the N-carbamoyl derivatives.

Some limitations of the subject surveyed have been necessary in order to keep the size of the chapter within the reasonable bounds. Accordingly, to make it not too long and readable, the discussion of the methods of the sulphoxide synthesis will be divided into three parts. In the first part, all the general methods of the synthesis of sulphoxides will be briefly presented. In the second one, methods for the preparation of optically active sulphoxides will be discussed. The last part will include the synthetic procedures leading to functionalized sulphoxides starting from simple dialkyl or arylalkyl sulphoxides. In this part, however, the synthesis of achiral, racemic and optically active sulphoxides will be treated together. Each section and subsection includes, where possible, some considerations of mechanistic aspects as well as short comments on the scope and limitations of the particular reaction under discussion. 

Reaction of alkyl phenylmethanesulphinates 100 with n-butyllithium in tetrahydro-furan at — 80 °C afforded the corresponding benzyl n-butyl sulphoxide160 (equation 53). Preparation of optically active sulphoxides by this reaction will be discussed later in this chapter. 

Further utility of the Andersen sulphoxides synthesis is demonstrated by the preparation of optically active unsaturated sulphoxides which were first prepared by Stirling and coworkers359 from sulphinate 276 and the appropriate vinylic Grignard reagents. Later on, Posner and Tang360 prepared in a similar way a series of ( )-l-alkenyl p-tolyl sulphoxides. Posner s group accomplished also the synthesis of (+)-(S)-2-(p-tolylsulphinyl)-2-cyclopentenone 287, which is a key compound in the chiral synthesis of various natural products361 (equation 159). 

The stereospecificity of the biological oxidation reactions has been exploited in the preparation of optically active sulphoxides. One enantiomer of the sulphoxide is oxidized to the sulphone faster than the other and so there is an excess of one enantiomeric sulphoxide after partial reaction has occurred164. 

Preparation of optically active P-aminoesters, P-aminonitriles, and P-aminocarbox-amides are of special relevance for the synthesis of enantiomerically pure P-aminoacids compounds of special relevance in several areas of medicinal chemistry. The resolution of P-aminoesters can be carried out by acylation of the amino groups or by other biocatalytic reactions of the ester groups, such as hydrolysis, transesterification, or aminolysis. The resolution of ethyl ( )-3-aminobutyrate... 

This conversion has been used as a key step in the preparation of optically active aziridines from optically active 1,2-diols (prepared by 15-46). ° Even hydrogen can be the leaving group. Benzylic hydrogens have been replaced by N3 by treatment with HN3 in CHCI3 in the presence of DDQ (p. 1511). °°... 

Compounds 137 and 138 are thus synthons for carboxylic acids this is another indirect method for the a alkylation of a carboxylic acid, representing an alternative to the malonic ester synthesis (10-104) and to 10-106 and 10-109. The method can be adapted to the preparation of optically active carboxylic acids by the use of a chiral reagent. Note that, unlike 132, 137 can be alkylated even if R is alkyl. However, the C=N bond of 137 and 138 cannot be effectively reduced, so that aldehyde synthesis is not feasible here. ... 

This route has been widely exploited because of the availability of a-amino azomethine compoimds from natural (S)-a-amino acids, through the corresponding a-amino aldehydes, which are configurationally stable provided that the amino function is suitably protected. Moreover, some a-amino acids are available with the R configuration and a number of enzymatic and chemical transformations have been described for the preparation of optically active unnatural a-amino acids. Overall, the route suffers from the additional steps required for protection/deprotection of the amino function and, in the case of hydrazones and nitrones, cleavage of the N - N or N - O bond. 

Chiral-at-metal cations can themselves serve as chirality inducers. For example, optically pure Ru[(bipy)3] proved to be an excellent chiral auxihary for the stereoselective preparation of optically active 3D anionic networks [M(II)Cr(III)(oxalate)3]- n (with M = Mn, Ni), which display interesting magnetic properties. In these networks all of the metalhc centers have the same configuration, z or yl, as the template cation, as shown by CD spectroscopy and X-ray crystallography [43]. 

Two contrasting conclusions have been reported in the reactions of lithium aluminium hydride in THF with phosphine oxides and phosphine sulphides respectively. The secondary oxide, phenyl-a-phenylethylphos-phine oxide (42), has been found to be racemized very rapidly by lithium aluminium hydride, and this observation casts some doubt on earlier reports of the preparation of optically active secondary oxides by reduction of menthyl phosphinates with this reagent. A similar study of the treatment of (/ )-(+ )-methyl-n-propylphenylphosphine sulphide (43) with lithium aluminium hydride has revealed no racemization. These results have been rationalized on the basis of the preferred site of attack of hydride on the complexed intermediate (44), which, in the case of phosphine oxides (X = O), is at phosphorus, and in the case of the sulphides (X = S), is at sulphur. Such behaviour is comparable to that observed during the reduction of phosphine oxides and sulphides with hexachlorodisilane. ... 

Although decarboxylation reaction seems to be a simple one-carbon removing reaction, it is demonstrated that this reaction is a unique and useful reaction in the preparation of optically active carboxylic acids. If the starting material is a racemic carboxylic acid, the optically active compound can be obtained via symmetrization by chemical carboxylation followed by asymmetrization via enzymatic reaction. Accordingly, the whole process can be said as chemicoenzymatic deracemization (Fig. 24). 

Levitt MS, RE Newton, SM Roberts, AJ Willetts (1990) Preparation of optically active 6 -fluorocarbocyclic nucleosides utilising an enantiospecific enzyme-catalysed Baeyer-Villiger type oxidation. J Chem Soc Chem Comm 619-620. 

The stereospecific conversion of menthyl arenesulphinates into chiral aryl methyl sulphoxides may also be achieved by means of methyllithium . The reaction of methyllithium with diastereoisomerically or enantiomerically pure arenesulph-inamides 283 was found to give optically active aryl methyl sulphoxides 284 (equation 156). The preparation of optically active sulphoxides 285 and 286, which are chiral by virtue of isotopic substitution (H - D and - respectively), involves the reaction of the appropriate non-labelled menthyl sulphinates with fully deuteriated methyl magnesium iodide (equation 157) and with benzylmagnesium chloride prepared from benzyl chloride labelled with carbon (equation 158). 

By modification of the elegant method of preparation of optically active sulfinates previously reported by Mikolajczyk and coworkers , an efficient stereospecific method for the conversion of readily available optically active sulfinamides to optically active sulfinates of inverted configuration at the sulfinyl function, has been recently reported by Hiroi and coworkers . The same authors subsequently reported the thermal rearrangement of several optically active cis- and trans-y-substituted allylic p-toluenesulfinates to optically active chiral sulfones with high stereoselectivity. For example, trans and cis (S)-( — )-crotyl p-toluenesulfinates rearranged to optically active (S)-(-l-)- and (R)-( — )-a-methylallyl p-tolyl sulfone, respectively (equation 19). 

Intramolecular asymmetric hydrosilylation-oxidation of (alkenyloxy) hydrosilanes provides an efficient method for the preparation of optically active polyols from al-lylic alcohols. Cyclization of silyl ethers 54 of a meso-type allyUc alcohol in the pres-... 

Scheme 8.15. Preparation of optically active polysubstituted decalines by a lipase-catalyzed domino esterification/Diels-Alder reaction.

The optically active glycols are a convenient starting material for the preparation of optically active carbinols, hydroxy-acids, etc. The biological method of asymmetric reduction is perhaps the only convenient method for the preparation of these glycols. The steps in the preparation of other optically active glycols arc identical with those of /-propylene glycol. In some cases it is found convenient to oxidize the chlorohydrin to the... 

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