Stereospecific preparation

The benzilic acid rearrangement of steroid a-diketones is often the preferred method for ring contraction. Yields are generally excellent, and in several instances the reaction has been shown to be stereospecific. Preparation of the starting a-diketones is discussed below and illustrated with several excellent experimental procedures. 

As in the case of aldol addition, the scope of conjugate addition reactions can be extended by the use of techniques for regio- and stereospecific preparation of enolates and enolate equivalents. If the reaction is carried out with a stoichiometrically formed enolate in the absence of a proton source, the initial product is the enolate of the adduct. The replacement of a tt bond by a ct bond ensures a favorable AH. 

Kanegafuchi Chemical Industries produce D-p-hydroxyphenyl glycine, which is a key raw material for the semisynthetic penicillins ampicillin and amoxycillin. Here, an enantioselective hydantoinase is applied to convert the hydantoin to the D-p-hydroxyphenyl glycine. The quantitative conversion of the amide hydrolysis is achieved because of the in situ racemization of the unreacted hydantoins. Under the conditions of enzymatic hydrolysis, the starting material readily racemizes. Therefore, this process enables the stereospecific preparation of various amino acids at a conversion of 100% [38]. 

The stereospecific preparation of aldehyde ester 462, already comprising five of the six stereo centers of the molecule and, furthermore, the stereoselective construction of the epialloyohimbane skeleton with Ec2 conformation are regarded the remarkable features of Woodward s approach. 

The procedure most commonly used for the stereospecific preparation of optically active sulfoximides involves the reaction of optically active sulfoxides with arylsulfonyl azides in the presence of copper (98,118,131,178,179). This reaction occurs with retention of configuration at sulfur and with high stereospecificity. The stereospecific sulfoxide-sulfoximide conversion is a key reaction in the stereospecific sulfoxide-sulfimide-sulfoxiraide set of interconversions carried out by Cram and co-workers (98) and shown in Scheme 9. A similar cycle of interconversions studied independently by Andersen and co-workers (179) was used to determine the stereochemical course of the sulfoxide-sulfoximide transformation (see Scheme 10). 

The effect of the BF3 activation on the regioselectivity of the ring opening of vinylic and acetylenic oxiranes is dramatic, as in these conditions the reaction occurs exclusively on the allylic " or the propargylic " position, and still with inversion (Scheme 40). This excellent regioselectivity allows the direct stereospecific preparation of homoallylic and homopropargylic alcohols in excellent yields. In the case of acetylenic oxiranes, a remarkable difference in the reactivity of cis and trans oxiranes has been evidenced, the former being more reactive. 

Scheme 17.42 Stereospecific preparation of/S,/S-disubstituted / -amino acids.

The preparation of fluorinated dienes is particularly advantageous via the palladium catalyzed coupling protocol. By proper selection of the appropriate vinylzinc reagent and vinyl iodide, a wide variety of fluorinated dienes can be stereospecifically prepared, as illustrated in equation 22. 

The stereospecific preparation of Z- ,/l-dill uorostyrenes was accomplished by Davis and Burton via modification of the Heinze methodology, as illustrated in equation 4937,38. The Z- /,/i -di II uorostyrenes could be readily converted to other synthons, such as E- /i-di -/ -iodostyrenes ( -FIC=CFPh) and -a, / -difluoro-/ -tributylstannanes (E-PhFC=CFSnBu3), by known literature reactions38, and which could be utilized as synthons in other coupling reactions. 

The stereospecific preparation of E- and Z-a-fluorovinylstannanes via the radical reaction of the corresponding a-fluorovinylsulfones with tributyltin hydride has been reported by McCarthy et al. These reagents undergo a variety of destannylation reactions including protolysis, deuterolysis, acylation, iodina-tion, electrophilic fluorination and the Stille coupling reaction [186-189] (Scheme 66). The last reaction has been employed successfully in the synthesis of a fluorinated thymidylate synthetase inhibitor [189] (Scheme 67). 

Stereospecific preparation of PhCHDCHDX compounds by this route has not been successful application of both the top and bottom sequences in Scheme 9 to phenylacetylene results in the same product... 

The stereospecific preparation of cis- and tra s-oxiranes can be achieved from the same diol via the acetal. The trans-oxirane is obtained via the glycol monotosyl ester and the c/s-oxirane via the bromohydrin ester (Eq. 53). ... 

A publication discussing the uses of reactive arsonium ylides for the stereospecific preparation of epoxides draws attention to the fact that arsonium salts are less readily prepared than phosphonium salts because of the poorer nucleophilicity of arsenic compared to phosphorus, and suggests methods for obtaining them. Primary salts were made from alkyl triflates, while a-branched salts were prepared from alkyldiphenylarsines, obtained from iodo compounds as, for example, in equation 23. Reaction of alkyl halides with arsines to form arsonium salts is also promoted by the presence of silver tetra-fluoroborate . 

Banks, M R, Cadogan, JIG, Gosney, I, Gaur, S, Hodgson, P K G, Highly regio- and stereospecific preparation of a new carbohydrate-based l,3-oxazin-2-one by the INIR method and its appUcation in some asymmetric transformations. Tetrahedron Asymmetry, 5, 2447-2458, 1994. 

A variety of functionalized unsymmetrical (Z)- or ( )-enediynes 131 or 132 are stereospecifically prepared in good overall yield is an experimentally straightforward one-pot procedure involving two sequential Pd (PPh3)2 and PdCl2(PhCN)2 catalyzed coupling reactions from (Z)- or ( )-l,2-dichloroethene and 1-alkynes [Eqs. (44) and (45)] [65]. 

For regiodefined alkenylboranes, cleavage of the vinylic carbon-boron bond with deuterioacetic acid provides a simple, stereospecific preparation of deuterium-substituted alkenes. ... 

A transition metal catalyzed synthesis of ethers by carbene insertion into the O—bond has been reported. Not only saturated but also unsaturated alcohols can be utilized in this catalytic process. ° Intermolecular and intramolecular oxirane ring opening reactions by alkoxides and phenoxides also provide efficient and stereospecific preparations of acyclic and cyclic ethers. The procedures have been surveyed in detail. ... 

As described above, 1,2-azido alcohols can be stereospecifically prepared from epoxides. 1,2-Azido alcohols thus prepared reacted with triphenylphosphine or trialkyl phosphites to afford aziridines, where inversion of both centers of the original epoxides takes place (Scheme Intramolecular oxirane... 

Oestreich, M., Hoppe, D. Stereospecific preparation of highly enantiomerically enriched organomagnesium reagents. Chemtracts 2001, 14, 100-105. 

Eisch, J.J., and GaUe, J.E., Stereospecific preparation of 1,2-epoxyalkyllithium reagents via the generalized lithiation of a-heterosubstimted epoxides, J. Organomet. Chem., 121, CIO, 1976. 

Plata, D.J., Leanna, M.R., and Morton, H.E., The stereospecific preparation of an hydroxyethylene isostere precursor via a novel piperidine-2,5-dione template. Tetrahedron Lett.. 32, 3623, 1991. 

In an earlier example of the applicability of cuprate chemistry to C-glycosidations, Bellosta, et ai.,26 stereospecifically prepared epoxides from protected glucals (Scheme 2.3.4). Unfortunately, as shown in the previous example, the use of acetate protecting groups instead of benzyl protecting... 

D-p-Hydroxyphenyl glycine is a key raw material for the semisynthetic penicillins such as ampidllin and amoxycillin. It is also used in photographic developers. Racemic hydantoins are synthesized starting from phenol derivatives, glyoxylic acid and urea via the Mannich condensation (Fig. 19-28). The D-specific hydantoinase is applied as immobilized whole cells in a batch reactor. The unreacted L-hydantoins are readily racemized under the alkaline conditions (pH 8) of enzymatic hydrolysis, yielding quantitative conversion. This process enables the stereospecific preparation of various amino acids, such as L-tryptophane, L-phenylalanine, D-valine, D-alanine... 

Treatment of the initial stannane with potassium fluoride/ iodine results in the stereospecific preparation of the diiodide 18.134... 

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