Synlanti selectivity

In a more complex scenario, the /J-substituents were also found to participate in partially matched or mismatched reactions577. Examples of double induction pave the route of polypropionate and polyketide synthesis and it was emphasized that the relative influence of the enolate or aldehyde component may be enhanced, depending on the coordinating metal employed in the double stereodifferentiating aldol reaction. Thus, it was found that, in spite of their modest synlanti selectivity, lithium enolates are effective in double stereodifferentiating aldol reaction578. In the matched and partially matched cases, lithium enolate face selectivity is opposite to that which is found for their boron or titanium counterparts. This is perfectly illustrated in a recent work by Roush and coworkers reporting a partial synthesis of Bafilomycin Aj (Scheme 122)579. 

Scheme 9 Transition states rationalizing synlanti selectivities of Wittig rearrangements...

In connection with studies on chirality transfer in 2,3-Wittig rearrangements, Tsai and Midland examined the ( )- and (Z)-( )-l-isopropyl-2-butenyl benzyl ethers (131 equation 32) and (135 equation 33). Both ethers rearranged with essentially complete suprafaciality, but the (Z)-isomer (135) showed considerably higher ( )/(Z) and synlanti selectivity in accord with transition state considerations previously discussed for the analogous propargylic ethers (Scheme 7). 

In contrast to the solution photochemistry, irradiation of the crystals of le provided remarkably high diastereoselectivities in the formation of 2e. The temperature at which the reaction occurs is important in determining dia-stereoselectivity. At 15 °C, the de of syn-2e was 61% and the ratio of synlanti was 8.7, which was the reverse of that in the solution reaction (synlanti=0.9). The solid-state photoreaction proceeded even at -78 °C, and with higher diastereo-selectivity. At low conversion (9%), only syn isomers (de=93%) were obtained, and 71% de was observed even at 90% conversion. 

Boron enolates of a-benzyloxy esters.1 The triflate 1 converts alkyl benzyloxy-acetates (2) into the boron enolate, which readily undergoes aldol reactions with high yyn-diastereoselectivity. Somewhat higher syn-selectivity obtains with dicyclopen-tylboryl triflate, whereas use of LDA results in slight anti-selectivity (synlanti=34-37 66-63). Diisopropylethylamine is essential for the aldol reaction. Syn-3 is re-... 

The nitroaldol condensation with nitromethane (Henry s reaction), followed by Nef decomposition of the resultant nitronate under strongly acidic conditions, has been used to elongate aldehydes. For instance, A-acetyl-D-mannosamine has been converted into A-acetylneuraminic acid applying this method iteratively [69]. Chikashita and coworkers [70] have reported good levels of anti diastereoselectivity better than 99% in an iterative homologation sequence using 2-lithio-l,3-dithiane [71] with 2,3-O-cyclohexylidene-D-glyceraldehyde R)-62. In the case of the BOM-protected tetrose derivative, the addition of 2-lithio-l,3-dithiane was syn selective (synlanti 82 18) (Scheme 13.30). 

The results of experiments on the reduction on 5-substituted adamantanones 1 and 5-azaadamantan-2-one N-oxide (2) with NaBHq show that electron-withdrawing substituents favour attack by the complex hydride syn to the substituent or nitrogen [30, 34, 51] (Fig. 6-17). In the case of 2, the effect is striking, with a synlanti attack ratio of 96/4 for the formation of the anti syn alcohols respectively (Table 6-1). Electron-donating substituents show a marginal preference for anti attack. Similarly, syn facial selectivity is found in free-radical reactions [63], ther-... 

A stereogenic center on the tether (44a), composed of a relatively small hydroxyl substituent, results in the four possible product isomers shown in Figure 16. The designations anti and syn isomers refer to the orientation of the tether substituent and the adjacent carbonyl group in the product. Alcohol 44a yields all four possible products, and trans is preferred over cis by a factor of 2.5 or 4.2, depending on the solvent. The primary difference in the product ratios comes from the solvent-dependent synlanti ratio. In the protic solvent methanol, the anti isomers comprise 85% of the product whereas in the aprotic methylene chloride the syn isomers are 56% of the mixture. The syn selectivity may result from an intramolecular hydrogen bond of the alcohol to the nearby carbonyl (see pro-trans-syn conformation). Steric enhancement of the alcohol as a /-butyldimethylsilyl ether (44b) results in a solvent independent anti-selective photoreaction. The amount of syn isomers produced with a t-butyldimethylsilyloxy substituent is less than 1%. ... 

The most efficient synthetic route was a condensation of methyl arylphosphinates 283 with oxazolidine 280. Precursors 283 were prepared by esterification of corresponding phosphinic acid, using a procedure described by Afarinkia (Scheme 56) [201]. When //-phosphinic acids were not commercially available, they were obtained by pallado-catalyzed arylation of anilinium hypophosphite [202]. The condensation gave a mixture of two diastereomers synlanti). The last step was selective epimerization at the phosphorus atom in concentrated HCl. 

Regardingionicliquidimmobilization,differentpyrrolidine-basedorganocatalysts have been synthesized and demonstrated excellent selectivities synlanti >99/1, >99% ee) for the conjugate addition of cyclohexanone to nitrostyrenes [136]. These catalysts are easily recovered by precipitation, extraction, or filtration and reused for several cycles. Representative examples (95-97) of some of the most active systems are depicted in Fig. 2.11. 

In 2009, Carter and Yang reported the construction of the novel proline-based catalyst 27, which is soluble in most solvent systems, including industrially attractive solvents such as 2-Me-THF, and is readily made from inexpensive starting materials [23], Several experiments were conducted to validate the scope of this new catalyst (Scheme 5.16). For instance, propionaldehyde (2d) was reacted with A(-Boc-protected aldimine 23k to provide the Mannich product 25j in excellent selectivity (15 1 dr syn/mA, 99% ee), while L-proUne (1) furnished the same product in rather poor diastereoselectivity (1.2 1 dr synlanti), 99% ee). Similar results were obtained for differently substituted aldimines 23a, 23c-d and 231 as well. 

Me2NB) prepared with 16f. At high monomer concentrations [M], the rate of polymerization is essentially independent of [M] with a rate constant of k = 6.1 x 10 /s at 20 C. This value is very similar to ksyn/anti = 7 x 10 /s determined for the synlanti rotamer interconversion of 16f at 25 °C. This means that the rate-determining step in the chain propagation of 1,7,7,-MC3NB polymerization is the transformation of the syn alkylidene into the anti form, and thus confirms that the mechanism of cis/trans selectivity outlined in Schemes 20.16 through 20.19 applies to several ROMP monomer/catalyst combinations. 

Z)-Enolates of 9-BBN, on treatment with benzaldehyde in chloroform at -78 °C, give high yields of aldol products with over 96% syn selectivity (Scheme 6.30 Table 6.30). The (Z)-enolates derived from catecholborane afford synlanti aldols in poor ratio as compared to when derived from 9-BBN. 

An aldol reaction of a silyl enol ether with an aldehyde has been carried out in water, with a chiral copper(II) bis(oxazoline) catalyst, with moderate to good ee and synlanti ratios." Conveniently performable in aqueous ethanolic solution for typical reactants, the reaction does not merely tolerate water, but its course and selectivities are dependent on it. 

Several factors must be considered in selecting a crotyl metal or allyl metal reagent for use in an acyclic stereoselective synthesis. First, it is necessary that the new stereocenters generated in concert with the new C—C bond (Scheme 1) be formed with a high degree of stereoselectivity. This is the problem of simple diastereoselectivity. Two diastereomeric products may be produced, and in this chapter Masa-mune s synlanti nomenclature system will be used to describe them. Second, the issue of diastereofacial selectivity is encountered if the aldehyde (or other C=X reaction partner) is chiral. This is a problem of relative diastereoselectivity, and four products may be produced in the reactions of the crotyl oiganome-tallics (Scheme 2). The diastereofacial selectivity issue is also critical in the reactions of allyl metal reagents and chiral C=X electrophiles. 

When reactions are conducted with unsymmetrical dienophiles, the low selectivity of the intermolecular tandem cycloadditions becomes apparent [167c]. Thus, the use of propene leads to the formation of the expected product 450 (Scheme 16.91) in 78% yield however, as a mixture of six isomers. Head-to-taU configuration slighdy predominates (1.5/1) and the ratio synlanti untilsyn synisyn diastereomers of the products is 5.6/8.4/1. In comparison, the more hindered isobutene reacts much more slowly (190 °C, 30 h, 36%) however, more selectively and less than 15% of the isolated product forms head-to-head. The antilsyn-selectivity has not been determined for this reaction. Styrene reacts forming a selectively antilanti head-to-taU product. The en /o-selectivity may be due to the secondary orbital interactions with this unhindered dienophile, although the yield is low (11%) due to the alkene polymerizafion. 

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