Derivatives, diastereoisomeric

For 1,3-dithiolanes the ring is flexible and only small energy differences are observed between the diastereoisomeric 2,4-dialkyl derivatives. The 1,3-oxathiolane ring is less mobile and pseudoaxial 2- or 5-alkyl groups possess conformational energy differences (cf. 113 114) see also the discussion of conformational behavior in Section 4.01.4.3. 

Br. CHa. CHa. CHa. CH(NHa). CH(CHa). CHa. CHjBr HBr. which on treatment with dilute alkali gives di-heliotridane (II). As the latter contains two asymmetric carbon atoms, two diastereoisomeric racemates might be produced in this reaction but only one was formed. It had density and refractive index in general agreement with those recorded for Z-heliotridane, as were also the melting points of characteristic derivatives. Density Df °0-902, refractive index wf, 1-4638 (<. with Adams and Rogers,3i Df ° 0-935, iijf° 1-4641), picrate, m.p. 234-6° (literature 232-6°), picrolonate, m.p. 162-3°, aurichloride, m.p. 200-1° (Konovalova and Orekhov give for these two constants 152-3° and 199-200° respectively). 

Addition of the dianion of /5-sulphinylcarboxylic acids to carbonyl compounds leads to the formation of the corresponding hydroxy derivatives which undergo spontaneous cyclization to give y-lactones440. Bravo and coworkers have found that when optically active ( + )-(R)-3-(p-toluenesulphinyl)propionic acid 426 is used for this reaction, the corresponding diastereoisomeric / -sulphinyl-y-lactones 427 are formed in a ratio which is dependent on the substituents in the carbonyl component441,502 503 (equation 256). 

The use of ethyl ethylthiomethyl sulphoxide in this reaction leads to the desired addition products in much better yields (95-97%). These products were then converted into ketene dithioacetal monoxide derivatives 430 by a sequence of reactions (equation 258)505. Reaction of 2-lithio-l,3-dithiane-l-oxide with benzophenone affords a mixture of the diastereoisomeric tertiary alcohols 431 in a ratio which is temperature dependent (cis trans changes from 3 1 at — 78 °C to 1 1 at room temperature)268. 

The synthesis of highly substituted rigid tricyclic nitrogen heterocycles via a tandem four-component condensation (the Ugi reaction)/intramolecular Diels-Alder reaction was investigated in both solution and solid phase [24]. The Ugi reaction in MeOH (Scheme 4.2) involves the condensation of furylaldehydes 17, benzylamine 18, benzyl isocyanide 19 and maleic or fumaric acid derivatives 20, and provides the triene 21 which immediately undergoes an intramolecular Diels-Alder reaction, affording the cycloadduct 22 in a diastereoisomeric mixture with high yield. 

Bohman and Allenmark resolved a series of sulphoxide derivatives of unsaturated malonic acids of the general structure 228. The classical method of resolution via formation of diastereoisomeric salts with cinchonine and quinine has also been used by Kapovits and coworkers " to resolve sulphoxides 229, 230, 231 and 232 which are precursors of chiral sulphuranes. Miko/ajczyk and his coworkers achieved optical resolution of sulphoxide 233 by utilizing the phosphonic acid moiety for salt formation with quinine. The racemic sulphinylacetic acid 234, which has a second centre of chirality on the a-carbon atom, was resolved into pure diastereoisomers by Holmberg. Racemic 2-hydroxy- and 4-hydroxyphenyl alkyl sulphoxides were separated via the diastereoisomeric 2- or 4-(tetra-0-acetyl-D-glucopyranosyloxy)phenyl alkyl sulphoxides 235. The optically active sulphoxides were recovered from the isolated diastereoisomers 235 by deacetylation with base and cleavage of the acetal. Racemic 1,3-dithian-l-oxide 236... 

The title reaction may be accomplished by using various reducing agents. Thus benzyl a, a-dichlorobenzyl sulphoxide 496 was reduced to a mixture of diastereoisomeric benzyl a-chlorobenzyl sulphoxides 497 by means of (Me2N)3P/EtjN in aqueous solvent, BujSnH, Ph3P/Et3N in methanol and CrCl (equation 301). Similarly, dichloro-bis(phenylsulphinyl)methane is reduced to the corresponding monochloro derivative . ... 

This procedure has been recently applied to the synthesis of L-lyxitol and the polyhydroxylated chain of amphotericin Interesting results have also been obtained in the reduction of ) -oxo derivatives of dithioacetal monoxides. In the reaction sequence of equation 322 two successive asymmetric inductions are involved. After the first reaction, involving acylation of the carbanion, a diastereoisomeric mixture in a 65 35 ratio is produced. When this mixture is reduced with NaBH4 in MeOH-conc. aqueous solution of ammonia, among four possible diastereoisomeric alcohols, the stereoisomer 523 is obtained with a stereoselectivity of 98% . Guanti and coworkers have found that the LiAlH4 reduction of the same substrates at — 78° in THF/ether leads to 523 with a stereoselectivity 99 i6i3.6i4... 

As an alternative process, the nitrone (138 R Cl OCl Ph) yields a mixture of diastereoisomeric (benzyloxymethyl)phosphonic derivatives of which (141) is the main component acidolysis and hydrogenolytic debenzylation lead to phosphoserine (143), the (S) chirality of which was demonstrated by )(-ray analysis of the derivative (144). In a further variation, the di-tert-butyl... 

Several acyl derivatives of (aminomethyl)-and (1-aminoethyl)-phosphonic acids, in the latter case including [L-l-([L-alanyl]amino)ethyl]phosphonic acid (alafosfalin), have been prepared in their various diastereoisomeric forms and the... 

The stereoselective allylation of carbon-nitrogen multiple bonds have also been studied. The addition of allylzinc bromide to aromatic imines derived from (. S j-valine esters was affected by reversibility, which caused the lowering of the diastereoisomeric ratio with increasing reaction time. The retroallylation reaction could be avoided by performing the reaction in the presence of trace amounts of water or by using CeC - 7H2O as the catalyst with a decreased reaction rate.71... 

Similarly, both diastereoisomeric alcohols (164 and 165) derived from 8-alkylcycloberbines gave again the C-8—N bond cleavage products. The... 

The 8-methyl-8,14-cycloberbine 364, derived from the protoberberine 324 via the betaine 363, was reduced with sodium borohydride or lithium aluminum tri-tert-butoxyhydride to give a diastereoisomeric mixture of cis-and trans-alcohols (7.8 1 or 1 7.8, respectively) (Scheme 64).t)n exposure to formaldehyde the mixture underwent N-hydroxymethylation and subsequent intramolecular substitution on the aziridine ring to give the oxazolidine 365. Removal of the hydroxyl group in 365 was accomplished by chlorination followed by hydrogenolysis with tributyltin hydride. Reductive opening of the oxazolidine 366 with sodium cyanoborohydride afforded ( )-raddeanamine (360), which has already been converted to ochotensimine (282) by dehydration. 

The spirobenzylisoquinoline 171b derived from berberine (15) (Section IV,A,1) was oxidized with m-chloroperbenzoic acid to the /V-oxide 389, which was treated with trifluoroacetic anhydride to afford dehydrohydrastine (370) in 56% overall yield (Scheme 71) through the Polonovski reaction (187). Holland et al. (188,189) reported the reverse reaction from dehydrophthalides to spirobenzylisoquinolines, namely, 370 was reduced with diisobutylalu-minum hydride to give a mixture of two diastereoisomeric spirobenzylisoquinolines 320 and 348 via the enol aldehyde. This reaction was applied to synthesis of various spirobenzylisoquinoline alkaloids such as (+)-sibiricine (352), ( + )-corydaine (347), (+ )-raddeanone (354), ( )-yenhusomidine (359), (+ )-ochrobirine (343), and ( )-yenhusomine (323). 

Diastereoisomeric transition states calculated for propene insertion in a model for a Brookhart-type Ni(II) catalyst, based on diacetylbis(2,6-diisopro-pylphenylimine)nickel derivative,143,144 are shown in Figure 1.21. Diastereomeric transition states for si (Figure 1.21a) and re (Figures 1.21b,c) monomer insertions into a si chain correspond to like (isotactic) and unlike (syndiotactic) propagations, respectively.144,143... 

Cyclic orthoformates are useful intermediates for the synthesis of butenolides (235). Treatment of D-ribonolactone, or its 5-0-substituted derivatives, with one molar equivalent of ethyl orthoformate gave diastereoisomeric... 

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