Diastereoselective preparation

For the purpose of stereoselective synthesis the selective elimination at the stage of the /3-hydroxysilane 5 is not a problem the diastereoselective preparation of the desired /3-hydroxysilane however is generally not possible. This drawback can be circumvented by application of alternative reactions to prepare the /3-hydroxysilane 2 however these methods do not fall into the category of the Peterson reaction. 

Two closely related methods for the diastereoselective preparation of <5-oxo esters have been developed. The first method uses the chelated lithio enamine 2. These Michael donors are readily available from the tert-butyl ester of L-valine and jS-oxo esters. The Michael addition of this lithio enamine 2 to 2-(arylmethylene)propanedioates, followed by hydrolytic removal of the auxiliary, provides d-oxo esters with contiguous quaternary and tertiary carbon centers with high diastereoselectivity59 60. 

Diastereoselective preparation of a-alkyl-a-amino acids is also possible using chiral Schiff base nickel(II) complexes of a-amino acids as Michael donors. The synthetic route to glutamic acid derivatives consists of the addition of the nickel(II) complex of the imine derived from (.S )-,V-[2-(phenylcarbonyl)phenyl]-l-benzyl-2-pyrrolidinecarboxamide and glycine to various activated olefins, i.e., 2-propenal, 3-phenyl-2-propenal and a,(f-unsaturated esters93- A... 

Oxidation of cyclic phosphonoformaldehyde dithioacetal, using the Modena protocol, yields the trans disulfoxide 121 in excellent enantiomeric excess. Then 121, via HWE olefination and oxidation of the double bond has been used for the diastereoselective preparation of spirocyclic his-sulfinyl oxiranes (new versatile intermediates in asymmetric synthesis) [79] (Scheme 37). 

These conditions were well suited for the preparation of 5-hydroxyesters, lactones, and -5-hydroxy nit riles. Moreover, the usefulness of substituted titanocenes for enantio- and diastereoselective preparation of these products has been demonstrated as shown in Scheme 10 [68-72],... 

Scheme 37 Diastereoselective preparation of spiro-P-lactams using Mukaiyama s reagent...

G. Bellucci, G. Catelani, C. Chiappe, and F. D Andrea, A simple and highly diastereoselective preparation of glycal epoxides using the MCPBA-KF complex, Tetrahedron Lett., 35 (1994) 8433-8436. 

Ziegler149 has reported a highly efficient synthesis of the very similar M. avium serovar 21 trisaccharide hapten with attached linker-arm (89). The blockwise construction minimizes the manipulation of protecting groups and hence the number of steps in the overall synthesis. The synthesis featured two key operations (1) the kinetically controlled diastereoselective preparation from D-glucose of the... 

Silyl migrations from O to C were also found during the synthesis of a-halomethylsilanes415 and diastereoselective preparations of (Z)-vinyl-, epoxy- and cyclopropylsilanes389,416. 

This reaction applied to diallyllactones allowed the diastereoselective preparation of exo-methylene spirolactones [ 14] (Eq. 9). 

Enantiomeric enriched a-thiosulfoxides 391 can be prepared by addition of a-thiomethyllithiums to p-tolyl sulfinate601. The deprotonation of p-tolyl (p-tolylsulfanyl)methyl sulfoxide (403) took place with w-BuLi at — 78 °C to afford the enantioenriched lithium derivative 404602. The addition to benzaldehyde followed by methylation of the hydroxy group and deprotection gave a-methoxyphenylacetaldehyde with 70% ee. This chiral formyl anion gave diastereoselectively Michael addition to a-substituted cyclopentenones603. The acylation of compound 404 followed by LAH reduction allowed the diastereoselective preparation of compounds 405 up to 99% de (Scheme 105)604. 

Figure 2.18. Diastereoselective preparation, by templated threading, of [3]-rotaxane 45, using hydrophobic interactions. [2]-rotaxane 46 and free-dumbbell 47 are also produced in this reaction.

Amuilations of pyridinium- and quinolinium-salts however have not been reported so far. From the addition reactions of C-nucIeophiles like Grignard, organozinc and organotin reagents to pyridinium- and quinolinium-salts have been reported to be valuable methods for the construction of substituted dihydropyridine [4a-4d] and dihydroquinoline-derivatives [4d-4e] results of our studies in the field of benzothiopyrylium-salts [5] we concluded that the sequential intermolecular 1,2-addition/intramolecular 1,4-addition of 4-silyloxyquinolinium-salts 1 with 2-silyloxy-l,3-butadienes 2 might be useful for the diastereoselective preparation of annulated quinolones 3. 

The Lewis acid-promoted carbonyl-ene reaction of enantiomerically pure 4-oxoazetidine-2-carbaldehydes gave homoallylic alcohols, which have been used for the diastereoselective preparation of fused bicyclic, tricyclic and tetracyclic p-lactams of non-conventional structure 49 and 50, using tandem one-pot radical addition/cyclization or elimination-intramolecular Diels-Alder sequences <03JOC3106>. 

The hydrosilylation-oxidation of simple unfunctionalized alkenes has not been widely used for the diastereoselective preparation of alcohols, probably because it would not in general be expected to give very different results to hydroboration oxidation. One example which has been reported is the exo-selective hydrosilylation of norbornene (1) with trichlorosilane and hexachloroplatinic acid6, followed by oxidation to c.vo-norbornanol (2)1. 

The oxidation of A-alkoxyamines with lead tetraacetate generated aziridines, albeit in low yields (<20%)9 11. Despite the almost complete diastereoselectivity claimed in the preparation of A-methoxyazi ridine 1 from methoxyamine and ( )-2-butene loss of the geometrical purity was observed in the reaction of excess ( )- and (Z)-2-butene with A-(butoxy)aminc in dichloro-methane to give 2n. For this reason a two-step mechanism involving an intermediate N Pb species or nitrenium ion was proposed. However, the completely diastereoselective preparation of both trans- and cis-2 was successively claimed by different authors (GC-MS analysis)49. 

Control of the absolute stereochemistry was possible starting from the optically active substrate. Initial attempts by protecting the hydroxy function as a j8-oxo ester were unsuccessful146. However, the use of triisopropylsilyl protective group allowed the diastereoselective preparation of the vinylaziridine which was then converted to 6,7-diepicastanospermine140. 

Whereas in dichloromethane the ene product is obtained from ( )- and (Z)-2-butenes and 4-phenyl-3//-l, 2,4-triazolc-3,5(4//)-dione (6), by performing the reaction in methanol the attack of methanol on the structurally rigid aziridinium imide intermediate allows the diastereoselective preparation of syn- and anri-l-(2-methoxy-l-methylpropyl)-l,2,4-triazolidine-3,5-diones together with minor amounts of the ene products11. Similar results are obtained with linear 1,3-dienes (Section 7.2.10.3.10.1.). 

The solution-phase synthesis and resolution of new phosphinopeptidic building blocks containing a triple bond and their involvement in 1,3-dipolar cycloaddition with a variety of in j// -prepared nitrile oxides allowed the diastereoselective preparation of a novel class of isoxazole-containing phosphinic peptides 619. Inhibition assays of some of these peptides revealed their behavior as very potent inhibitors of metalloproteases, outmatching previously reported phosphinic peptides in terms of potency <2003CEJ2079>. 

In conclusion, this scheme allows the ready diastereoselective preparation of cyclopropane derivatives of high enantiomeric excess (> 95% ee) presenting high synthetic potential. 

Scheme 6.50 Diastereoselective preparation of P-stereogenic phosphinates via DSRCM.

Scheme 10.122 Diastereoselective preparation of monoprotected 1,2-alkenyl-3,4-diols in a one-pot synthetic sequence [104].

This methodology was subsequently extended to the reaction with ketones, which allowed the diastereoselective preparation of adjacent quaternary aU-carbon stereogenic centers in an acyclic system [105]. In the case of ethoxyacetylene 360, the alkenylcopper derivatives 361 were formed quantitatively, followed by homologation with a zinc carbenoid and reaction of the resulting aUenylzinc intermediates with ketones (Scheme 10.124). 

Roush and co-workers used olefin metathesis as a key step in their enantioselective and diastereoselective preparation of several cyclic P-... 

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