Selectivity Diastereoselectivity

Diastereoselective Acetal Fission Followed by Benzylation (Step 2). Upon treatment with KHMDS and 18-crown-6 in THF at —78 °C, the acetal from the (/f,/ )-bis-sulfoxide is rapidly converted into the alkoxide having the (lS,2f ) configuration. The counter cation of the base is very important for high selectivity. Diastereoselectivity was seen to increase in the order LiHMDS (8% de) 96% de). 

The antifungal, antiviral agent (+)-brefeldin A, whose recent synthesis using rr-allyl-paUadium complexes has previously been described (Scheme 24), was prepared by Trost et using the [3 + 2] cycloaddition to form the cyclopentyl ring (Scheme 41). Chiral acrylate 190, prepared from mannitol, was subjected to cyclizalion conditions to give cycloadduct 191 in 87% yield and an excellent selectivity. Diastereoselectivity in the cycloaddition extended the stereochemistry of 190 into the absolute stereochemistry of 191, generating three of the live stereocenters of brefeldin A. After ozonolysis, reduction, and protection, the lower side chain was attached to prepare the sulfone 192. The upper side chain was then introduced, and further functionalization led to the key intermediate 194, which had already been transformed to (+)-brefeldin A. 

Silver(I) salts are often utilized as catalysts for addition reactions. Kozmin and Sun have recently shown that AgNTf2 is a catalyst of choice for the hydroamination of siloxy alkynes with either secondary amides or carbamates to give silyl ketene am-inals [34]. The addition occurs in a syn selective manner, for instance, the reaction of siloxy alkyne (24) with carbamate (25) produces silyl ketene aminal (26) in 86% yield at room temperature under the influence of 1 mol% of AgNTf2 (Scheme 18.9). A six-membered chelated transition state is proposed to explain the high syn selectivity. Diastereoselective bromohydroxylation and bromomethoxylation reactions of cinnamoyl compounds possessing a chiral auxiliary are also effectively promoted by silver(I) salts such as AgNOs [35]. The asymmetric halohydrin reaction has been successfully applied into stereoselective syntheses of (-)-chloramphenicol and (+)-thiamphenicol. Csp-H iodination [36], hydrosilylation of aldehydes [37], and deprotection of TMS-alkynes [38] are also catalyzed by silver (I) salts. 

An anti-selective diastereoselective aldol reaction [14] has been performed by using enantiomerically pure carboxylic esters derived from (-) or (+) norephedrine 30 [15], This method is applicable to a wide range of aldehydes with high selectivity (both syn/anti and diastereoselectivity of anti isomer). It is proposed that ( ) boron enolates 31 are formed by this procedure and aldol reaction proceeds via the six-membered transition state (Eq. (14)). The aldol products 32 are converted to the corresponding alcohols (LiAlH4 THF) or carboxylic acids (LiOH, THF-H2O) without loss of stereochemical integrity. 

Key words Spherand-type calixarene, ion selectivity, diastereoselective functionalization. 

Oren, J., Vardi, M., Viskin, R., Abramson, S., and Fuchs, B., Homoconjugated ketones with extended unsaturation wavelength selective, diastereoselective and enantiospecific photochemical transformations of methyl 7-oxospiro[5.5]undeca-l,3-and 2,4-diene-2-carboxylate, Helv. Chim. Acta, 76, 1182, 1993. 

Guindon Y, Godin F, Mochirian PA, PrevostM. Selected diastereoselective reactions free radical additions and cyclizations. In Carreira EM, Yamamoto H, eds. Comprehensive Chirality. Amsterdam Elsevier 2012 472—503. 

The prochiral meso form of 2-cyclopenlen-1,4-diol (101) reacts with the (Z)-alkenyl iodide 102 to give the 3-substituted cyclopentanone 103 with nearly complete diastereoselectivity (98 2)[92], The reaction is used for the synthesis of prostaglandin. The alkenyl iodide 102 must be in the Z form in order to obtain the high diastereoselectivity. The selectivity is low when the corresponding (Z)-alkenyl iodide is used[93]. 

Asymmetric synthesis is a method for direct synthesis of optically active amino acids and finding efficient catalysts is a great target for researchers. Many exceUent reviews have been pubHshed (72). Asymmetric syntheses are classified as either enantioselective or diastereoselective reactions. Asymmetric hydrogenation has been appHed for practical manufacturing of l-DOPA and t-phenylalanine, but conventional methods have not been exceeded because of the short life of catalysts. An example of an enantio selective reaction, asymmetric hydrogenation of a-acetamidoacryHc acid derivatives, eg, Z-2-acetamidocinnamic acid [55065-02-6] (6), is shown below and in Table 4 (73). 

The key step to this first reported case of the highly diastereoselective addition of a fluorinated enolate in an aldol process is the selective formation of the enolate a,a-Difluonnated enolates prepared by a metallation process employing either a zinc-copper couple [S] or reduced titanium species [9] undergo aldol condensation smoothly (equation 9) (Table 5)... 

The initial investigation focused on the use of threitol-derived auxiliaries with various substituent groups on the dioxolane ring (Table 3.3). However, it became evident that the oxygen atoms in the substituents had a detrimental effect on selectivity. Comparison of the diastereoselectivities for the ketals 69-71, which contain Lewis basic sites in the substituents at the 1 and 2 positions, with those from simpler diol derived ketals 72-74 demonstrates the conflicting effects of numerous coordination sites. The simpler, diol-derived ketals provide superior results compared to the threitol derived ketals. The highest diastereoselectivity is observed in the case of the 1,2-diphenyl ethane-1,2-diol derived ketal 74. 

Ni(C104)2 6H2O showed a litde better enantioselectivity than the anhydrous complex. Although the uncatalyzed reaction was highly exo selective (cis/trans=i 97), the catalyzed reactions were very poor in diastereoselectivity, a mixture of endo and exo cycloadducts being formed. We expected that this poor diastereoselectivity would not be a serious problem since the same enantioface should be involved at the 2-position of the diastereomeric cycloadducts (Scheme 7.27). The best enantioselectivity (cis > 99% ee, trans 94% ee) was observed when the reaction was catalyzed by l ,J -DBFOX/Ph-Ni(SbF6)2 (50 mol%). With the decreased amount of catalyst (10 mol%) still a satisfactory level of enantioselectivity was observed for the cis cycloadduct (94% ee). 

Sinidar observations were made in a related series of unsaturated pbospban oxides isLicli as 73, Sclieme G.14) [29], Wliereas dialkylcuprates mostly reacted not selectively, tlie best diastereoselectivities were observed for disilylaiprates (7i). 

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. 

An expedient and stereoselective synthesis of bicyclic ketone 30 exemplifies the utility and elegance of Corey s new catalytic system (see Scheme 8). Reaction of the (R)-tryptophan-derived oxazaboro-lidine 42 (5 mol %), 5-(benzyloxymethyl)-l,3-cyclopentadiene 26, and 2-bromoacrolein (43) at -78 °C in methylene chloride gives, after eight hours, diastereomeric adducts 44 in a yield of 83 % (95 5 exo.endo diastereoselectivity 96 4 enantioselectivity for the exo isomer). After reaction, the /V-tosyltryptophan can be recovered for reuse. The basic premise is that oxazaborolidine 42 induces the Diels-Alder reaction between intermediates 26 and 43 to proceed through a transition state geometry that maximizes attractive donor-acceptor interactions. Coordination of the dienophile at the face of boron that is cis to the 3-indolylmethyl substituent is thus favored.19d f Treatment of the 95 5 mixture of exo/endo diastereo-mers with 5 mol % aqueous AgNC>3 selectively converts the minor, but more reactive, endo aldehyde diastereomer into water-soluble... 

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