Chiral p-alkoxy

Chiral 1,3-diols. Chiral p-alkoxy aldehydes react with compounds of the type RTiCI, at - 78° to form derivatives of 1,3-diols with high 1,3-asymmetric induction (equation I). High 1.3-asymmctric induction is also observed in aldol condensations of these aldehydes catalyzed by TiCL (equations II and III). 

High 1,3- and 1,4-asymmetric induction is possible in addition reactions to chiral P-alkoxy aldehydes. The reaction with allylsilanes catalyzed by TiC shows high diastcr-eofacial selectivity (equation II). Essentially only one. vv -adduct of two possible dias-tereomers is obtained in reactions with silyl enol ethers (equation III). 

Enders and coworkers <96AG(E)1725> have developed an interesting general one-pot method for the asymmetric epoxidation of enones with oxygen in the presence of diethylzinc and (l ,/ )-N-methylpseudoephedrine (30), which provides a, P - epoxyketones in very high yield and high enantiomeric excess (e.g., 33 —> 34). The actual reactive species is believed to be the chirally modified alkoxy(ethylperoxy)zinc 31, which attacks the si face of the s-cis conformation of the (E) enones (cf. 32). 

McKervey and Ye have developed chiral sulfur-containing dirhodium car-boxylates that have been subsequently employed as catalysts for asymmetric intramolecular C-H insertion reactions of y-alkoxy-ot-diazo-p-keto esters. These reactions produced the corresponding ci -2,5-disubstituted-3(2H)-furanones with diastereoselectivities of up to 47% de. Moreover, when a chiral y-alkoxy-a-diazo-p-keto ester containing the menthyl group as a chiral auxiliary was combined with rhodium(II) benzenesulfoneprolinate catalyst, a considerable diastereoselectivity enhancement was achieved with the de value being more than 60% (Scheme 10.74). 

In most cases, the stereochemical course of heterocyclic addition can be altered by pre-complexation of nitrones with Lewis acids. In the absence of complexation agents (Et2AlCl, TiCLi), addition of lithio-hetaryl derivatives to chiral 3-alkoxy nitrones (292a-d) gives P-alkoxy-a-hydroxylamino-2-alkylhetaryls (346a-d) in good yields with. vy/i-selectivity. In the presence of diethylaluminum chloride the reaction leads to the same adducts, but with anti-selectivity (Scheme 2.150) (Table 2.12) (581). 

The azomethine yhde derived from 79 has also been used in reactions with chiral ( )-y-alkoxy-a,p-unsaturated esters 80 (Scheme 12.27). The corresponding tetra-substituted pyrrolidines 81 were obtained with complete regiocontrol in fair to excellent de (125). 

Aldol condensation of a-amino silyl ketene acetals (l).10 2-Dibenzylami-noketene trimethylsilyl acetals (1) react with aldehydes premixed with TiCl4 to give a-amino-p-hydroxy carboxylic esters (2) with moderate to high syn-selectivity. Surprisingly, TiCl4-catalyzed reaction of 1 with a chiral a-alkoxy aldehyde proceeds with low asymmetric induction. 

Angew Int 23 556 (1984) (chelation and non-chelation control in addition reactions of chiral a- and p-alkoxy carbonyl compounds) 30 49 (1991) (enantioselectivity)... 

Lithium divinyl cuprates. The addition of. inylic cuprates to chiral -y-alkoxy-a,p-unsaturated ketones and esters proceeds with high diastercoselectivity the major product is that in which the vinyl group is anti to the ally lie alkoxyl group. The geometry of the unsaturated system docs not affect the stcrcocheiiiistry of the addition. 

Marshall, J A, Seletsky, B M, Luke, G P, Synthesis of protected carbohydrate derivatives through homologation of threose and erythrose derivatives with chiral y-alkoxy allylic stannanes, J. Org. Chem., 59, 3413-3420, 1994. 

High diastereoselectivities in p-chelation-controlled reactions have also been observed with aldehydes and ketones in the presence of a Lewis acid where the chiral center is 3 to the carbonyl group, resulting in 1,3-asymmetric induction - The high diastereoselectivity observed in the reaction shown below, using Lil as the Lewis acid arises from 3-chelation of both the ketone and the ether oxygen with Li. This locks the conformation of the P-alkoxy ketone chain, and the hydride attacks from the less hindered side. ... 

Stereoselective addition of a dithiane anion to chiral 2-metiiyl-3-trimethylsUyl-3-butenal combined with the stereoselective addition of a Grignard reagent to the chiral a-alkoxy ketone affords a practical method for the construction of a, y-dimethyl-a,p-dihydroxy compounds, useful intermediates for the synthesis of erythronolides (Scheme 33). -Hydroxy carboxylic esters were synthesized by the addition of ethyl 1,3-dithiolanyl-2-carboxylate enolate to a chiral aldehyde, followed by desulfurization. ... 

Masamune and coworkers have examined the facial selectivity of the (Z)-lithium enolates of 3-penta-none and ethyl cyclohexyl ketone with a series of P-alkoxy aldehydes having stereocenters at both the a-and p-position (equation 110 Table 18). In the six-mernbered chelate, the methyl and R groups are on the same side of the ring, and it may be seen from the data in Table 18 that the nature of R influences the facial preference of the chiral aldehyde. Another example of this effect is seen in equation (54). 

TiCU-mediated addition of silyl enol ether (95) to chiral a-amino aldehyde (94) was reported to proceed with good chelation control, albeit in poor yield (equation 28). Effective chelation control was also reported in the TiCU-mediated reactions of chiral a-alkoxy and p-alkoxy acyl cyanides (96) and (97) with silyl enol ether (95 equations 29 and SO). Reaction of acyl cyanide (97) with the ( )-silyl enol ether (93) gave a single stereoisomer as a result of complete chelation control and syn simple stereoselection (equation 31). Additions of silyl enol ethers and silyl ketene acetals to (-)-menthyl phenyl-glyoxylate and pyruvate were reported to proceed with moderate facial selectivity the best result (84 16) is shown in equation (32). ... 

In the Held of chiral electrophiles, diastereoselective additions of enolsilanes to chiral a-fluoro-a-methyl-P-alkoxy aldehydes, a-methyl aldehydes, a-alkoxy aldehydes, a,p-dialkoxy aldehydes and a-methyl-P-alkoxy aldehydes were reported to proceed with good stereocontrol following Felkin-Anh or chelation models (c/. Section 2.4.4.1). Very good selectivities were reported in the addition of enolsilanes to chiral imines, particularly those derived from carbohydrates (Scheme 17 and 18).i. 6... 

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