Aldehydes stereoselective additions

Stereoselective Addition of Dialkylzincs to Chiral Aldehydes. Stereoselective addition of dibutylzinc to racemic 2-phenylpropanal using (1S,2J )-DBNE as a chiral catalyst affords optically active alcohols (84% ee, 92% ee) as a result of the si face attack of the aldehyde regardless of its configuration (eq 21). ... 

The stereoselective addition of 5-(3-ethylpent-3-yl) thiopropanoate can be mediated in a similar way using the C2-asymmetric (/ ,/J)-l-chloro-2,5-diphenylborolane of 92 93% enantiomeric purity70,71, Once again, the ( )-0-enolate forms, and its addition to achiral aldehydes delivers essentially diastereomerically pure products (antijsyn >155 1). The corrected ee values range from 94 to 100%70. 

Lower stereoselectivities arise, however, from the addition of ester enolates to this glyceralde-hyde4. Another highly stereoselective addition is in the synthesis of erythromycin A where a single product results from the addition of lithiated tert-butyl thiopropanoate to the enantiomerically pure aldehyde (2/ ,3/ ,4,S, 6/ ,7/ ,8,S, 9/ ,10.S, 11 / )-7-acetoxy-3,4 9,10-bis(isopropy1-idenedioxy)-11-methoxymethoxy-2,4,6,8,10-pentamethyltridecanal5. 

The naphthyl derived ligand, (5)-1-mcthyl-2-[(l-naphthylamino)methyl]pyrrolidine (4) is especially effective in the stereoselective additions of (Z)-l-cthylthio-l-trimethylsilyloxy-l-propene to aldehydes. Thus, quantitative formation of. yyn-adducts is achieved, in addition to high reagent-induced stereoselectivity (>98% ee for the 3-hydroxy thioester products)23 32. 

I.3.5.6.4. Stereoselective Addition of Enantiomerically Pure Nitronates to Aldehydes... 

Using FmA catalysis and protected 4-hydroxybutanal, compound (97) has been stereoselectively prepared as a synthetic equivalent to the C-3-C-9 fragment of (-F)-aspicillin, a lichen macrolactone (Figure 10.35) [160]. Similarly, FruA mediated stereoselective addition of (25) to a suitably crafted aldehyde precursor (98) served as the key step in the synthesis of the noncarbohydrate , skipped polyol C-9-C-16 chain fragment (99) of the macrolide antibiotic pentamycin [161,162]. 

Trialkylstannyl enolates can be prepared from enol acetates by reaction with trialkyltin alkoxides and are sufficiently reactive to add to aldehydes. Uncatalyzed addition of trialkylstannyl enolates to benzaldehyde shows anti stereoselectivity.31... 

Recently, ///)H.YL has been found to catalyze the stereoselective addition of nitroalkanes to aldehydes in an. S -selective fashion, which is in agreement with the known stereopreference of this enzyme. This is the first example for a substitution of HCN by another carbon nucleophile, expanding the synthetic scope of this biocatalytic transformation. The addition of nitromethane to different aldehydes with moderate to good yields and enantioselectivity has been demonstrated (Figure 5.9) [58]. However, large amounts of enzyme are required to... 

The cyclopropylphosphonate anion undergoes the stereoselective addition reaction with aldehydes [106]. Although the Wittig-Horner elimination is not observed at this stage, the olefinic compounds are produced by treatment of the adduct alcohols 201 with NaH in the presence of 18-crown-6 as illustrated in Scheme 76. 

Triisopropylsilyloxyfurans were effective nucleophiles for the vinylogous Mannich addition to iminium ions that were formed by Rh2(cap)4-catalyzed oxidation of N-alkyl groups by THYDRO <06JA5648>. A stereoselective addition of 2-trimethylsilyloxyfurans to aryl aldehydes-derived aldimines employing a chiral phosphine/Ag complex as catalyst was developed <06AG(I)7230>. The prototypical example is shown below. 

Not only acyclic but also cyclic dienes can be employed to form t]3-aiiyititanium complexes. The complexes derived from 1,3-cyclopenta- and 1,3-cyclohexadiene undergo highly stereoselective addition with aldehydes (Scheme 13.11) [23]. 

Silyltitanation of 1,3-dienes with Cp2Ti(SiMe2Ph) selectively affords 4-silylated r 3-allyl-titanocenes, which can further react with carbonyl compounds, C02, or a proton source [26]. Hydrotitanation of acyclic and cyclic 1,3-dienes functionalized at C-2 with a silyloxy group has been achieved [27]. The complexes formed undergo highly stereoselective addition with aldehydes to produce, after basic work-up, anti diastereomeric (3-hydroxy enol silanes. These compounds have proved to be versatile building blocks for stereocontrolled polypropionate synthesis. Thus, the combination of allyltitanation and Mukayiama aldol or tandem aldol-Tishchenko reactions provides a short access to five- or six-carbon polypropionate stereosequences (Scheme 13.15) [28],... 

Stereoselective addition of cuprates to aldehydes Addition of Bu2CuLi to the formyl group of methyl y-oxocarboxylates (1) results in wans-disubstituted y-lactones (2) with high selectivity. The stereoselectivity is ascribed to chelation,... 

Wynberg3 has also effected stereoselective addition of (C2H5)2Zn to aryl aldehydes using cinchona alkaloids, particularly quinine and quinidine, which result in (R)- and (S)-alcohols in excess, respectively. The highest enantiomeric excess, 92% ee, was observed with o-ethoxybenzaldehyde catalyzed by quinine. 

The stereospecific reduction of a 2-butyne-l, 4-diol derivative and silver( I)-mediated cyclization of the resulting allene were successively applied to a short total synthesis of (+)-furanomycin 165 (Scheme 4.42) [68], Stereoselective addition of lithium acetylide 161 to Garner s aldehyde in the presence of zinc bromide afforded 162 in 77% yield. The hydroxyl group-directed reduction of 162 with LiAlH4 in Et20 produced the allene 163 stereospecifically. Cyclization followed by subsequent functional group manipulations afforded (+)-furanomycin 165. 

Table 9.18 Stereoselective addition of allenic titanium reagents to aldehydes.

SCHEME 19. Preparation of dibromoalkene 40 and stereoselective addition of bromolithioalkene 41 to aldehydes. Thex = Me2CHCMe2... 

SCHEME 21. Synthesis of N-protected a-amino acids and aldehydes by stereoselective addition of bromohthioalkene 5 -41 to sulfonyhmines. Mukaiyama aldol reaction of a-aminoaldehydes... 

Oxynitrilases are enzymes that catalyze the formation and cleavage of cyanohydrins through the stereoselective addition of hydrogen cyanide to aldehydes or methyl ketones giving enantiopure a-hydroxynitriles. The use of (R)-oxynitrilases for the preparation of chiral cyanohydrins has dramatically grown in the last decade because of their possibihties as precursors for the synthesis of many compounds with physiological properties [50]. 

Ooi has recently reported application of chiral P-spiro tetraaminophosphonium salt 37 as a catalyst for the highly enantio- and diasterioselective direct Henry reaction of a variety of aliphatic and aromatic aldehydes with nitroalkanes (Scheme 5.51) [92]. Addihon of the strong base KO Bu generates in situ the corresponding catalyhcally active triaminoiminophosphorane base A. Ensuing formation of a doubly hydrogen-bonded ion pair B positions the nitronate for stereoselective addition to the aldehyde. This catalyst system bears many similarities to guanidine base catalysis. 

Stereoselective addition to aldehydes is another powerful tool in organic chemistry. Two very specihc types of this reaction include allylation of aldehydes and cyanohydrin formation. These are both reactions that can beneht from the use of chiral bis(oxazoline) ligands.Two examples are summarized in Figure 9.53. 

Several DHAP aldolases having different stereospecificities were tested for their acceptance of this phosphonomethyl substrate mimic as the aldol donor, individual enzymes belonging to both Glass 1 and 11 types were found to catalyze the stereoselective addition of 14 to various aldehydes, providing bio-isosteric non-hydrolyzable analogues of sugar 1-phosphates in high yields (for example, 16/17 Scheme 2.2.5.7) [25, 26]. 

The results described in the following, part of which have been presented as a preliminary communication, are collected in a full paper. A. Dondoni, S. Franco, F. Junquera, F. L. Merch n, P. Merino, T. Tejero, and V. Bertolasi, Stereoselective homologation-amination of aldehydes by addition of their nitrones to C-2 metalated thiazoles. A general entry to a-amino aldehydes and amino sugars, Chem. Eur. J. 1 505 (1995). 

Complete details are available concerning stereoselective addition of these reagents to chiral aldehydes or ketones and of crotyltitanium compounds to carbonyl groups (12, 354).2 The most diastereoselective additions to cyclohexanones known to date are effected with organotitanium reagents. 

Stereoselective addition to an a-alkoxy aldehyde.3 The addition of organo-metallic reagents to acrolein dimer 1 can be controlled to a remarkable extent by the metal, evidently as a result of chelation, with R2Zn being more stereoselective than RLi or RMgBr. 

Eyer, M. Seebach, D. I-2-Nitro-l,3-alkanediols by stereoselective addition of nitroethanol to aldehydes. On the asymmetric electrophilic addition to double bonds. /. Am. Chem. Soc. 1985, 107, 3601-3606. 

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