Single diastereomer

Stevens reported an interesting variation in which the amine and the aldehydes were linked by a tether. Combining bisacetalamine 79 with 76 under acidic conditions generated the single diastereomer 80. This tricyclic species was then converted into the ladybug defense alkaloid precoccinelline 81. 

Treatment of substituted pyrollidinone 42 with a Lewis acid, rather than simple protic acid, lead to a Pomeranz-Fritsch-Bobbitt type condensation to yield indolizinone 43 as a single diastereomer. ... 

The validity of the model was demonstrated by reacting 35 under the same reaction conditions as expected, only one diastereoisomer 41 was formed, the structure of which was confirmed by X-ray analysis. When the vinylation was carried out on the isothiazolinone 42 followed by oxidation to 40, the dimeric compound 43 was obtained, showing that the endo-anti transition state is the preferred one. To confirm the result, the vinyl derivative 42 was oxidized and the intermediate 40 trapped in situ with N-phenylmaleimide. The reaction appeared to be completely diastereoselective and a single diastereomer endo-anti 44 was obtained. In addition, calculations modelling the reactivity of the dienes indicated that the stereochemistry of the cycloaddition may be altered by variation of the reaction solvent. 

The reaction of 5-methoxy-2(5//)-furanone 168 with amines was also studied (89T6799). The conjugated addition of ethanolamine to the furanone 168 gave the racemic amino lactone 275 (R = CH2CH20H). Similarly, piperazine reacted with two equivalents of 168 to provide the diadduct 276 as a single diastereomer (no traces of the other isomer were detected). With tryptamine, the reaction was nearly quantitative with the the formation the tran -adduct 277 (R = tryptophanyl) (Scheme 72) (89T6799). 

Modification of the ketonic side chain is also consistent with retention of analgesic activity. Thus, reduction of methadone with lithium aluminum hydride affords the alcohol, 128 (apparently as a single diastereomer). Acetylation gives acetyl-methadol (129). ... 

The chiral enamines provide the opportunity for the enandoselecdve Michael addidon to nitroalkenes, as shown in Eq. 4.68, where the ketone is obtained as a single diastereomer with anee>90%. ... 

Scheme 6a presents the synthesis of fragment 15. Intermediate 15 harbors two vicinal stereogenic centers, and is assembled in a very straightforward manner through the use of asymmetric aldol methodology. Treatment of the boron enolate derived from 21 with 3-[(p-methoxybenzyl)oxy]propanal (22) affords crystalline syn aldol adduct 34 in 87 % yield as a single diastereomer. Transamination to the A-methoxy-A-methylamide,20 followed by silylation of the secondary hydroxyl group at C-19 with triethylsilyl chloride, provides intermediate 15 in 91 % yield. 

The Diels-Alder adduct 8 formed in a mixture with 7 by treatment of porphyrin 6 with dimethyl acetylenedicarboxylate undergoes a base-induced migration of a C —C double bond yielding a single diastereomer 9 with the thermodynamically favored tram arrangement of the methyl group and the methoxycarbonyl substituent.201... 

Solladie-Cavallo s group used Eliel s oxathiane 1 (derived from pulegone) in asymmetric epoxidation (Scheme 1.3) [1]. This sulfide was initially benzylated to form a single diastereomer of the sulfonium salt 2. Epoxidation was then carried out at low temperature with the aid of sodium hydride to furnish diaryl epoxides 3 with high enantioselectivities, and with recovery of the chiral sulfide 1. 

To control the first factor, one of the two lone pairs of the sulfide must be blocked such that a single diastereomer is produced upon alkylation. For C2 symmetric sulfides this is not an issue, as a single diastereomer is necessarily fonned upon alkylation. To control the second factor, steric interactions can be used to favor one of the two possible conformations of the ylide (these are generally accepted to be the two conformers in which the electron lone pairs on sulfur and carbon are orthogonal) [14], The third factor can be controlled by sterically hinder-... 

The C2 symmetry of sulfide 13 means that a single diastereomer is formed upon alkylation (Scheme 1.10). Attack from the Si face of the ylide is preferred as the Re face is shielded by the methyl group cis to the benzylidene group (28). Metzner postulates that this methyl group also controls the conformation of the ylide, as a steric clash in 27b renders 27a more favorable [16]. However, computational studies by Goodman revealed that 27a was not particularly favored over 27b, but it was substantially more reactive, thus providing the high enantioselectivity observed... 

In the case of sulfide 7 the bulky camphoryl moiety blocks one of the lone pairs on the sulfide, resulting in a single diastereomer upon alkylation. One of the conformations (29b) is rendered less favorable by non-bonded interactions such that conformation 29a is favored, resulting in the observed major isomer (Scheme 1.11). The face selectivity is also controlled by the camphoryl group, which blocks the Re face of the ylide. 

Treatment of sulfmylaziridine 73 (Scheme 3.23) with MeMgBr and then with tert-butyllithium gave aziridinyllithium 74, which reacted with ethyl chloroformate to afford aziridine-2-carboxylate 75 in 64% yield [70]. The reaction was stereospecific, giving 75 as a single diastereomer. 

When aziridine-2-carboxylic ester 124 (Scheme 3.44) was treated with 1 equivalent of TFA, 125 was formed as a single diastereomer in 80% yield [57]. Use of 10 equivalents of TFA resulted in the formation of N-trifluoroacetyl product 126. This... 

Freparatively useful induced diastereoselectivities have been reported mainly for 1,1-di-substituted allyllithium derivatives which bear carbanion-stabilizing substituents. l-[Methyl-thio-l-(trimethylsilyl)-2-propenyl]lithium106 and the appropriate 1-phenylthio107 derivative, generated from the allylic sulfide with sec-butyllithium, in the reaction with tetrahydropyranyl-protected pregnolone, furnish a single diastereomer. 

Finally, several examples of intramolecular allylboration have been reported 51,92 -95. These reactions are highly stereoselective and afford only a single diastereomer in each case. 

A chiral nonracemic cyclic allyl iodide was shown to react with excess chromium(II) chloride and (4-methoxyphenylmethoxy)acetaldehyde to yield a single diastereomer, which was converted to la,25-dihydroxy vitamin D332. 

The addition of the anion of the 1,3-dimethyl-2-butenyl sulfoxides to 2-cyclopentenone was examined2. The anion of rar-2-methyl-4-(phenylsulfinyl)-2-pentene gave a 50 50 mixture of ( )- and (Z)-y-1,4-adducts which differed in the relative configuration of the new stereocenter regarding the stereocenter at sulfur. That is, for either the (Z)- or the ( )-product there is complete asymmetric induction from the stereocenter at sulfur, but in the opposite direction. When the rm-butyl analog, ruc-4-(/wt-butylsulfinyl)-2-methyl-2-pcntcne, was reacted, it gave exclusively the ( )-adduct, likewise as a single diastereomer. 

In a study concerned with the synthesis of prostaglandins, it was reported that the anion of 3-phenylsulfinyl-l-octene underwent addition to 2-cyclopentenone to give a y-1,4-adduct (57%), which appeared to be a single diastereomer by 13C NMR16... 

Michael addition of the enolate of (42 )-4-rm-butyl-3-methyl-2-oxetanone to dimethyl (Z)-butenedioate yields a single diastereomer. This provides a method to control two new vicinal stereogenic centers one quaternary and one tertiary. The topicity of the addition is u with respect to the 3,3 -bond and l with respect to the 3, 4 -bondI09. 

An interesting approach to zr n.v-2,3-disubstituted cyeloalkanones is offered by auxiliary controlled intramolecular Michael additions. The diastereoselectivity depends on the chiral alcohol used193> l94. When the borneol derivative 7 was used as substrate, a single diastereomer of 8 resulted when the reaction was performed at 25 "C under thermodynamic control with a catalytic amount of sodium hydride in benzene. 

In a further extension of this method, the enolate of the bislactim ether cyclo(L-Val-Gly) or cyclo(L-Val-Ala) were added to methyl (Z)-3-chloro-2-butenoate. The adduct is again a (Z)- ,/l-unsaturated ester and was obtained as a single diastereomer (d.r. > 99 l)207. For further examples see references cited ill the text. 

The reaction of the enamines of cyclohexanones with a,ft-unsaluraled sulfones gives mixtures resulting from attack of the enamine at the a- and /(-carbons of the oc,/ -unsaturated sulfone. The ratio of x- and /1-adducts is dependent upon the reaction solvent, the geometry and structure of the sulfone1 4. The diastereoselectivity of these reactions is also poor. The reaction of lithium enolates of cyclic ketones with ( )-[2-(methylsulfonyl)ethenyl]benzene, however, gives bicyclic alcohols, as single diastereomers, that result from initial -attack on the oc,/ -unsaturated sulfone5. 

The addition of methyl 3-amino-2-butanoate to ( )-4-[(5 )-arylsulfinyl]-5-(2-chlorophenyl)-4-penten-2-one in refluxing methanol gave the dihydropyridine as a single diastereomer. The stereochemical outcome is rationalized as occurring from attack of the nucleophile on the conformation in which dipole-dipole repulsion is minimized17. 

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