Diastereofacial differentiation

Figure 6.3 Diastereofacial differentiation in titanium-catalyzed AE of secondary allylic alcohols.

The titaniated (25)-2,5-dihydro-2-isopropyl-3,6-dimethoxypyrazines derived from cyclo(L-Val, Gly) or cyclo(L-Val, Ala) (1, R1 = H, CH3) react with a,/I-unsaturatcd aldehydes exclusively by 1.2-addition (cf. nearly exclusive 1,4-addition of ,//-unsaturated ketones with cuprate complexes of 2,5-dialkoxy-3,6-dihydropyrazines, see Section D. 1.5.2.3.1.4.) in a highly diastereoselective mode to give virtually only the (l S,2R)-diastereoniers 2 ". In reactions with the corresponding lithiated pyrazines both regioselectivity and diastereofacial differentiation at C-2 are also remarkably high (dc 95 %), but the diastereomeric excess at C-l is substantially smaller (30 50%) ... 

The mechanistic analogy to the Streckcr synthesis becomes obvious in the addition of the isocyanide to the imine to produce the a-amino nitrilium intermediate. Since all four components are involved in this step, it might be expected that every chiral component (chiral groups R1, R2, R3, R4) contributes to diastereofacial differentiation in the nucleophilic attack on the imine. However, in peptide syntheses by four-component condensation5, the chiral isocyanide or a chiral carboxylic acid component has only limited influence on the diastereoselectivity of the a-amino amide formation5. 

Diastereofacial differentiation occurs upon cyclopropanation of the substituted oyclohexene 43 with methyl diazoacetate. Only the two stereoisomers endo-44 and exo-44 were found, both with a 5-anti methyl group 60). In contrast, the ring substituents in l-trimethylsiloxy-cyclohexenes 45 and 46 are not efficient for such a differentiation, so that the four possible diastereomers are actually formed. 

The very high diastereofacial differentiation in the dialkylation of 2 to 7 can be attributed to a unique conformation of 2 and its enolate 8. There is NMR evidence of 2, X-ray crystallographic analysis of (Z)-9 and molecular mechanics calculations on 2, all of which suggest that the trityl group is on the a-face of the enolate, as shown in 8, resulting in attack of the electrophile on the /3-face30. 

Upon facing the difficulty of stereochemical control in peptide alkylation events, Maruoka and coworkers envisaged that the chiral phase-transfer catalyst should play a crucial role in achieving an efficient chirality transfer, and consequently examined the alkylation of the dipeptide, Gly-L-Phe derivative 57 (Scheme 5.28) [31]. When a mixture of 57 and tetrabutylammonium bromide (TBAB, 2 mol%) in toluene was treated with a 50% KOH aqueous solution and benzyl bromide at 0°C for 4h, the corresponding benzylation product 58 was obtained in 85% yield with the diastereo-meric ratio (DL-58 LL-58) of 54 46 (8% de). In contrast, the reaction with chiral quaternary ammonium bromide (S,S)-lc under similar conditions gave rise to 58 with 55% de. The preferential formation of LL-58 in lower de in the reaction with (R,R)-lc indicated that (R,R)-lc is a mismatched catalyst for this diastereofacial differentiation of 57. Changing the 3,3 -aromatic substituent (Ar) of the catalyst 1 dramatically increased the stereoselectivity, and almost complete diastereocontrol was realized with (S,S)-lg. 

Step 4 Conformational bias minimizes interactions with the indicated Ar-H and sets the stage for diastereofacial differentiation in the directed hydrogenation of the double bond. Base-promoted attachment of the alkoxide to rhodium gives the product with high diastereoselectivity. 

Diastereofacial differentiation in the photooxygenation of alkylidene-substituted norbornenes has been investigated. For 5-cthylidenebicyclo[2.2.1]hept-2-cne, the principal products are exo-and enclo-10, which are formed in a 74 26 ratio (47%), and the regioisomeric norbornadiene 11 (23%)51. 

Therefore, the ground state conformation drastically influences the diastereofacial differentiation of the photohydroperoxidation. 

Considerable attention was given to the stereochemistry for the alkylation of metal enolates of y-butyrolactones during the past 1980 s decade. It is well recognized that electrophihc attack on the enolates of -substituted y-butyrolactones is controlled exclusively by the -substituent leading to the trans addition products . However, Iwasaki and coworkers reported the reverse diastereofacial differentiation in the alkylation of the enolates of a, S-dibenzyl-y-butyrolactones. These authors proposed that the factor controlling the selectivity in this case was allylic strain. Also, y-substituted y-lactones give stereoselective trans alkylation . ... 

FIGURE 10.8 Diastereofacial differentiation on nitro alkene 107 (Scheme 10.35, Ref. [92]). 

EIGURE 10.9 Diastereofacial differentiation on 0-glucosyl butadienes (Scheme 10.36 [84,85]). 

More recently, asymmetric intramolecular carbolithiation was described, either with a remote chiral center in a suitable position to promote a diastereofacial differentiation of the olefin [130] or with a chiral organolithium derivative [131]. In the former case, alkylation... 

Extension of this methodology to the use of chiral acetals such as (72 equation 19) to produce optically active secondary alcohols is found to be less efTicient than the ketal series. Alkyl Grignard reagents in ether (Table 18) provide the best selectivities (up to 90 10), while aryl and alkynyl organometallics show very little diastereofacial differentiation. ... 

Alkylations of P-substituted 6-lactone enolates occur anti to the substituent with high dia-stereoselectivity unless bulky groups are present at the a-position. " Then, conformational effects may lead to a reversal of the diastereofacial differentiation. Other 8-lactone enolates are alkylated with poor diastereoselectivity unless they are cu-disubstituted at the 7- and 6-positions. Still and Galynker have shown that remote substituents may exert a considerable amount of asymmetric induction in mediumring lactone enolate alkylations. The remote substituent can determine which of the lower energy conformations of the enolate are available for alkylation. ... 

The vast majority of stereoselective reactions in organic chemistry, especially in asymmetric synthesis, involve diastereofacial differentiation of a trigonal, sp -atom. The stereoelectronic considerations outlined in the introduction to this chapter afford a rare opportunity in stereoselective synthesis the preparation of a chiral organometallic in which the carbon bearing the metal is stereogenic. As a result of the... 

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