Diethylzinc addition to aldehydes

During our research in this field of small-ring heterocycles we found that functionahzed aziridines are attractive chiral catalysts, e.g., in the diethylzinc addition to aldehydes. Aspects of such uses of aziridines will be discussed as well. This overview does not pretend to be an exhaustive coverage of all existing literature on small-ring aza-heterocycles as that would require a separate monograph. Instead, emphasis is put on functionahzed three-membered aza-heterocycles, that were investigated in the author s laboratory [1], and relevant related literature. The older literature on these heterocycles is adequately summarized in some extensive reviews [2]. Chiral aziridines have been reviewed recently by Tanner [3], by Osborn and Sweeney [4], and by McCoull and Davis [5]. 

Consequently, matched/mismatched cases [25] can result, and indeed our investigations on cooperative effects of stereogenic elements in such systems revealed 9 be the matched case and 23 (which is also easily prepared by following a directed deprotonation-silylation-deprotonation-trapping-desilylation sequence [11]) to be the mismatched case in diethylzinc additions to aldehydes [26]. Later, these investigations were extended to more complex systems such as 24 [27], but ferrocene 9 still remains superior to all other compounds. 

Scheme 2.1.3.6 Diethylzinc addition to aldehyde 21. Conditions aldehyde 21 (0.5 mmol), ligand (5%), toluene (1 mL), diethylzinc (1.0 mL, 1.0 M in hexane, 2 equiv), 0 °C, 16 h under argon.

Table 4.2 Diethylzinc additions to aldehydes catalyzed by Ti(IV) complexes of lOd.

Isomers of ris-l-amino-2-indanol have attracted considerably less attention, although improved asymmetric inductions have been reported on several occasions. Diethylzinc addition to aldehydes with m-.V-disubslil tiled-1 -amino-2-indanols as catalysts yielded secondary alcohols with low enantiomeric excesses (40-50%),37 whereas r/.v-N-disubstituted-2-amino-1 -indanols led to increased selectivities (up to 80% ee) (see Section 17.3.2).46 High degrees of enantioselection were eventually achieved in the addition of diethylzinc to aliphatic and aromatic aldehydes with /raw.v-N-dialkyl-l-substituted-2-amino-l-indanols as catalysts (Scheme 17.25).47 Optimal results were obtained with bulky groups at the hydroxy-bearing carbon and at the nitrogen (R = Ph, R1 = ft-Bu), which led to the formation of (R)-l-phenylpropanol in 90% yield and 93% ee. 

Asymmetric amplification in the diethylzinc addition to aldehydes has been observed with many (3-amino alcohols as catalyst, presumably because of a reservoir effect similar to that discovered by Noyori et al. Asymmetric amplification has also been found for other classes of chiral catalysts—diamines, diols, titanium complexes, etc. The various examples are collected in Table 1. The... 

One of the emerging applications of 4,5-dihydroimidazole-based compounds is as chiral auxiliaries in metal complexes used for asymmetric synthesis for example, 457 in ruthenium-catalyzed DielsAlder reactions <2001 J(P 1)1500, 2006JOM(691)3445> 458 in diethylzinc addition to aldehydes <2003SL102> 459 in asymmetric intramolecular Heck reactions <20030L595> and 460 in ruthenium-catalyzed epoxidation <2005OL3393> and iridium-catalyzed hydrogenation of imines <2004TA3365>. 

Recent advances of the preparation of novel optically active organoselenimn compounds, mainly organic diselenides, and their application as chiral ligands to some transition metal-catalyzed reactions and also as procatalysts for asymmetric diethylzinc addition to aldehydes are reviewed. Recent results of catalytic reactions using some organoselenimn compounds such as aUylic oxidation of alkenes and its asymmetric version as well as epoxidation of alkenes are also summarized. 

Chiral Diselenides and Selenides as Procatalysts for Diethylzinc Addition to Aldehydes... 

Diols and diamines were also found to be highly efficient catalysts for this reaction. Recently it was shown that sulfur compounds containing amines are able to catalyze the diethylzinc addition to aldehydes [12]. 

The chiral ferrocenylselenium reagents were found to act as the effective ligands for Rh(I)-catalyzed asymmetric hydrosilylation and transfer hydrogenation (see Sects. 2.1 and 2.2, respectively). Fukuzawa and Tsudzuki have found that the chiral ferrocenylselenium-based amino alcohols (DASF), prepared by treatment of the chiral diferrocenyl diselenide with NaBH4 in ethanol followed by the addition of epoxides (Scheme 11), efficiently catalyzed the diethylzinc addition to aldehydes to provide the corresponding secondary alcohols with up to 99% ee... 

Wirth and co-workers used various chiral nitrogen-containing diselenides 20 - 24, which worked effectively as procatalysts for diethylzinc addition to aldehydes (see Sect. 3.1) [13] and for the catalytic oxyselenenylation-elimination reaction of frans- -methylstyrene (Scheme 26) [30]. Under the reaction conditions reported by Iwaoka and Tomoda [19], the diselenide 20 yields the product with highest enantioselectivity (up to 56% ee). Potassium peroxodisulfate seems to be superior to sodium and ammonium analogues. Effect of metal salts on stereoselectivity in the catalytic reaction using the diselenide 20 was investigated since it is known that metal ions can accelerate the decomposition of peroxo-... 

A large number of chiral a,a -orz/zo-disubstituted diphenyldiselenides with hydroxy and amino functions (e.g., 244 and 245) have been prepared by Wirth and co-workers. They were used as electrophiles for a number of asymmetric addition and cyclization reactions including the total synthesis of the lignan derivatives (-l-)-samin and (-l-)-membrine as well as catalysts in the asymmetric diethylzinc addition to aldehydes. 

Scheme 9.6 Enantioselective diethylzinc addition to aldehydes catalyzed by a tris-BINOL Ti coordination polymer.

Scheme 9.13 Chiral zirconium phosphonate hybrids-Ti-catalyzed enantioselective diethylzinc addition to aldehydes.

In addition to serving as a key stereochemical controlling element for synthesis of indinavir,5 the title compound has proven to be a remarkably versatile chiral ligand and auxiliary for a range of asymmetric transformations including Diels-Alder reactions,13 carbonyl reductions,14 diethylzinc additions to aldehydes,15 and enolate additions.16... 

A -( 3-Mercaptoethyl)pyrroldine 427, which is also C2 symmetric, was effective for catalysis of diethylzinc addition to aldehydes,as was the D-ribonolactone-derived hydroxypyrrolidine 428. ... 

The catalytic activity of polymer-supported chiral salen has been also studied in the enantioselective diethylzinc addition to aldehydes since the importance of this type of hgand in asymmetric catalysis. Soluble polymer-supported salens have been synthesized by Venkataraman... 

Chiral salen-type linear polymers have been prepared and tested in the diethylzinc addition to aldehydes [157]. The symetrical dialdehyde-containing compoimd 249 was first synthesized in five steps fi om 2-tertbutylphenol and allowed to react with 1,2-diaminocyclohexane and DPEN to afford the linear polymers 250 (Scheme 100). The catalytic activity of these chiral... 

Scheme 7.29 Asymmetric diethylzinc addition to aldehydes using silica-supported ligands 55 and 56.

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