2,2-disubstituted, chiral

N-substituted and N,N-disubstituted chiral a-amino nitrones are also available from the corresponding a-amino aldehydes. In a first study, it was shown that the addition of phenylmagnesium bromide to N-Boc derivatives exclusively gave the syn N-Boc a-aminohydroxylamines with good yields, but... 

Various N,N-disubstituted chiral dibromofluoromethylphosphonodiamides (292) have been easily prepared and reacted with tert-butyl acrylate in an asymmetric electrosynthesis of a-fluorinated cyclopropylphosphonoamides... 

Phosphorothioate and boranophosphate linkages introduced into DNA or RNA using nucleoside 5 -[a-thio]triphosphates and nucleoside 5 -[a-borano]tri-phosphates are more resistant to exo- and endonucleases than normal 3, 5 phosphodiester linkages. Combination of the two modifications yielded a novel non-bridging-disubstituted chiral a-triphosphate nucleoside, namely the thymidine 5 -[a-P-borano, a-P-thio] triphosphate (119). The synthesis was the modification of a procedure developed for the synthesis of nucleoside triphosphates and previously reported by the group. 

Similar thermochromic and solvatochromic effects have been observed by Bidan and coworkers71 for the optically active polymer 25 prepared in a regiospecihc fashion (100% HT-HT coupling) by the McCullough method. In contrast, the analogous regiorandom polymer prepared by oxidation with FeCl3 in chloroform has only weak optical activity. However, the disubstituted chiral polythiophene 26, synthesized by... 

The best discrimination is obtained for 1,2-disubstituted chiral ferrocene species their 1,3-disubstituted counterparts did not exhibit this chiral recognition. 

It is obvious that the chirality will be eroded if the p-hydride elimination occurs at the chiral a-position of tosyUiydrazones. The selectivity of p-hydride elimination in this reaction can be interpreted as follows. Alkylpalladium complex, the intermediate generated after migratory insertion of palladium carbene, is favorable to afford 1,1-disubstituted chiral olefin (Fig. 18, path a) because of the less steric interactions in the transition state at p-hydride elimination. Apparently the alternative syn p-hydride elimination will lead to the erosion of chiral center. However, the latter pathway is not preferred because it leads to the eclipse of the bulky substituent with the methyl group of the substrate (Fig. 17, path b). 

The general syntheses of alkenes (p. 28 — 44) and 1,2-dihydroxy compounds (p. 50—54 and 123 — 132) are not repeated here. But there is an important chiral pool" for chiral 1,2-disubstituted compounds, namely a-amino acids. 

Disubstituted cyclohexanes present us with a challenging exercise in stereochemistry Con sider the seven possible dichlorocyclohexanes 1 1 as and trans 1 2 as and trans 1 3 and as and trans 1 4 Which are chiral Which are achiral Four isomers—the ones that are achiral be cause they have a plane of symmetry—are relatively easy to identify... 

The same kind of spontaneous racemization oc curs for any as 1 2 disubstituted cyclohexane in which both substituents are the same Because such compounds are chiral it is incorrect to speak of them as meso compounds which are achiral by definition Rapid chair-chair interconversion however converts them to a 1 1 mixture of enantiomers and this mix ture IS optically inactive... 

The nonplanarity of allenes has an interesting stereochemical consequence 1 3 Disubstituted allenes are chiral they are not superimposable on their mirror images Even an allene as simple as 2 3 pentadiene (CH3CH=C=CHCH3) has been obtained as sep arate enantiomers... 

Chiral separations are concerned with separating molecules that can exist as nonsupetimposable mirror images. Examples of these types of molecules, called enantiomers or optical isomers are illustrated in Figure 1. Although chirahty is often associated with compounds containing a tetrahedral carbon with four different substituents, other atoms, such as phosphoms or sulfur, may also be chiral. In addition, molecules containing a center of asymmetry, such as hexahehcene, tetrasubstituted adamantanes, and substituted aHenes or molecules with hindered rotation, such as some 2,2 disubstituted binaphthyls, may also be chiral. Compounds exhibiting a center of asymmetry are called atropisomers. An extensive review of stereochemistry may be found under Pharmaceuticals, Chiral. 

Among chiral dialkylboranes, diisopinocampheylborane (8) is the most important and best-studied asymmetric hydroborating agent. It is obtained in both enantiomeric forms from naturally occurring a-pinene. Several procedures for its synthesis have been developed (151—153). The most convenient one, providing product of essentially 100% ee, involves the hydroboration of a-pinene with borane—dimethyl sulfide in tetrahydrofuran (154). Other chiral dialkylboranes derived from terpenes, eg, 2- and 3-carene (155), limonene (156), and longifolene (157,158), can also be prepared by controlled hydroboration. A more tedious approach to chiral dialkylboranes is based on the resolution of racemates. /n j -2,5-Dimethylborolane, which shows excellent enantioselectivity in the hydroboration of all principal classes of prochiral alkenes except 1,1-disubstituted terminal double bonds, has been... 

In the earlier, longer approach to (Z)-and (E)-alkenes, ThxR BH was used iastead of IpcR BH. It is also possible to prepare a-chiral acetylenes and alkanes by this method (76,520). In a shorter synthesis of a-chiral alkynes, a prochiral disubstituted (Z)-a1kene is hydroborated with... 

High enantioselectivities and regioselectivities have been obtained using both mono- and 1,2-disubstituted prochinal olefins employing chiral phosphine phosphite (33,34) modified rhodium catalysts. For example, i7j -2-butene ia the presence of rhodium and (12) (33) gave (3)-2-meth5ibutanal ia an optical yield of 82% at a turnover number of 9.84. ... 

Chiral nitrones react with alkenes to produce 3,5-disubstituted isoxazolidines that are nonracemic diastereomeric mixtures and are oriented predominantly cis (equation 53) (77CC303, 79JOC1212). 

As with i -substituted allyl alcohols, 2,i -substituted allyl alcohols are epoxidized in excellent enantioselectivity. Examples of AE reactions of this class of substrate are shown below. Epoxide 23 was utilized to prepare chiral allene oxides, which were ring opened with TBAF to provide chiral a-fluoroketones. Epoxide 24 was used to prepare 5,8-disubstituted indolizidines and epoxide 25 was utilized in the formal synthesis of macrosphelide A. Epoxide 26 represents an AE reaction on the very electron deficient 2-cyanoallylic alcohols and epoxide 27 was an intermediate in the total synthesis of (+)-varantmycin. 

Likewise, a cis-2,6-disubstituted piperidine natural product, (-)-lobeline (98, Scheme 8.4.30) was synthesized from the chiral Af-alkyl pyridinium salt ent-80 via a sequence that included addition of a Reformatsky reagent to an intermediate oxazolidine. °... 

Chiral 2,2-disubstituted l,3-benzoxazin-4-ones as auxiliaries in the synthesis of carbapenem antibiotics 97YGK858. 

Chiral N,N-disubstituted 2-(aminomethyl)pyrrolidines as catalysts for asymmetric acylation of alcohols 99YGK598. 

Chiral 4,5-disubstituted oxazolidin-2-ones in stereoselective synthesis of (3-hydroxy-a-amino acids 97G475. 

Disubstituted 2-oxazolidines as chiral auxiliaries synthesis from 2-oxazolones 97YZ339. 

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