Aldehydes, 2-hydroxy chiral

The sequence can also be used with aliphatic aldehydes it provides a general route to chiral hydroxy aldehydes, acids, and alcohols. 

Cram erythro-products" (G.E. Keck, 1984 A, B, C). [3-(Silyloxy)allyl]stannanes and O-pro-tected a- or y -hydroxy aldehydes yield 1,2,3- or 1,2,4-triols with three chiral centres with high regio- and diastereoselectivity (G.E. Keck, 1987). 

Cleavage of the oxathiane moiety can be carried out with iV-chlorosuccinimide/silver nitrate and leads to the a-hydroxy aldehyde 21 along with a diastereomeric mixture of sultines 20. The sultines can be reduced to the hydroxy thiol 22 which can be reconverted to the chiral auxiliary 16 in ail overall recovery of about 70%39. 

Cleavage of the addition product 5 can be easily performed by treatment with dilute ( 1 %) aqueous alcoholic hydrochloric acid which liberates the chiral amino alcohol 3 and an a-hydroxy aldehyde. The latter can be further oxidized to the oc-hydroxy carboxylic acid 6 with sodium chlorite33. 

Similarly, chiral nitrones (61a—c) and (62a—c) were obtained from the corresponding a-amino aldehydes (209, 210), nitrones (63a,b) from p-amino-a-hydroxy aldehydes (211), and chiral nitrones (64) and (65) from IV-fluorenyl-methoxycarbonyl (/V-Fmoc) amino acids and /V-Fmoc-dipeptides (Fig. 2.6) (212). 

Cyanohydrins are starting materials of widespread interest for preparing important compounds such as a-hydroxy acids/esters, a-amino acids, / -amino alcohols, a-hydroxy aldehydes, vicinal diols, and a-hydroxy ketones. Cyanohydrin compounds can be synthesized using various chiral catalysts such as cyclic... 

Oxidation of silyl enol ethers. Oxidation of silyl enol ethers to a-hydroxy aldehydes or ketones is usually effected with w-chloroperbenzoic acid (6, 112). This oxidation can also be effected by epoxidation with 2-(phenylsulfonyl)-3-( p-nitrophenyl) oxaziridine in CHC1, at 25-60° followed by rearrangement to a-silyloxy carbonyl compounds, which are hydrolyzed to the a-hydroxy carbonyl compound (BujNF or H,0 + ). Yields are moderate to high. Oxidation with a chiral 2-arene-sulfonyloxaziridine shows only modest enantioselectivity. 

The reaction was used for synthesis of (- )-norpseudoephedrine from a chiral a-hydroxy aldehyde (second example). The diastereoselectivity can be reversed by addition of alkyllithiums to a-trityloxy aldehydes, presumably because chelation with the oxygen atom is no longer possible. 

The chiral cyanohydrins also lead directly to a-hydroxy acids by hydrolysis (sequence B) [69] and to protected a-hydroxy aldehydes by first hydroxyl group protection, followed by reduction of the nitrile and hydrolysis of the intermediate imine (not shown) (sequence C) [114]... 

Since ketone R)-16 was prepared in a non-selective way when an achiral imino enolate was alkylated, it was considered whether alkylation of chiral enolates, such as that of oxazoline 18, with benzyl bromide 14, would provide stereoselective access to the corresponding alkylation product 19 with R-configuration at C(8) (Scheme 4). Indeed, alkylation of 18 with 14 gave the biaryl 19 and its diastereoisomer almost quantitatively, in a 14 1 ratio. However, reductive hydrolysis using the sequence 1. MeOTf, 2. NaBH4, and 3. H30", afforded hydroxy aldehyde 20 in 25% yield at best. Furthermore, partial epimerization at C(8) occurred (dr 7.7 1). An alternative route, using chiral hydrazones, was even less successful. 

Mukaiyama et al. developed a rather general and versatile method for the preparation of optically active a-hydroxyaldehydes by using the diamine (99) as chiral adjuvant. Thus, one Grignard reagent (R MgX) is reacted with the aminal (102) of methyl glyoxylate. In the next step a second kind of Grignard reagent (R2-MgX) is diastereoselectively added to the ketoaminal, and the desired chiral a-hydroxy-aldehyde (103) is obtained by hydrolysis 117-1I8). 

The scope of the present article comprises syntheses of sugar-type compounds containing four or more carbon atoms, an aldehyde or a ketone group, and a minimum of two hydroxyl groups (or their equivalents, such as amino or thiol groups) at least one of them being bound to a center of chirality. The subject of aldol-type reactions of formaldehyde and two- or three-carbon atom hydroxy aldehydes and hydroxy ketones has been omitted a comprehensive discussion of this topic, including a historical survey, has appeared in this Series.5... 

An unusual variation of the three-component process involves the use of unprotected carbohydrates 201, nature s chiral a-hydroxy aldehydes, as the carbonyl com-... 

Enantioselectivities of 21-70% ee were observed in the reaction of ethyl- and methyl-vinylketone with aromatic aldehydes 22 using the chiral hydroxy-pyrrolizidine-catalyst 24 which was prepared in four steps starting from BOC-I-prolinol (Scheme 5) [32]. The enan-tioselectivity was explained by the predominant formation of intermediate 26-A, which is less sterically hindered than the isomeric intermediate 26-B. The employment of a reaction temperature of -40 °C, the use of NaBF4 as a co-catalyst, and the presence of a hydroxy group in the base (which allows the formation of intramolecular hydrogen bonds) resulted in good conversions and rates. 

Diastereoselective addition of organometallic reagents to a-chiral aldehydes usually follows the Cram s rule or Felkin-Ahn model. However, the sense ot the Odiastereoselectivity in the catalysed addition of dialkylzinc to a-chiral aldehydes is determined not by the chirality of aldehyde but by the configuration of the chiral catalysts. By choosing the appropriate enantiomer of the chiral catalyst, one can obtain the desired diastereomer from the diastereoselective addition of dialkylzincs to a-chiral aldehydes.18 Either of the diastereomers of protected chiral 1,2-diols and 1,3-diols is synthesized using the appropriate enantiomer of the chiral catalysts [(15,2f )-l, (R,R)-15, and their enantiomers] from the addition of diorganozincs to protected a-hydroxy-19 and P-hydroxyaldehydes (Scheme 12.3).20... 

The hydroxynitrile lyase (HNL) class of enzymes, also referred to as oxynitrilases, consists of enzymes that catalyze the formation of chiral cyanohydrins by the stereospecific addition of hydrogen cyanide (HCN) to aldehydes and ketones (Scheme 19.36).275 279 These chiral cyanohydrins are versatile synthons, which can be further modified to prepare chiral a-hydroxy acids, a-hydroxy aldehydes and ketones, acyloins, vicinal diols, ethanolamines, and a- and P-amino acids, to name a few.280 Both (R)- and (.S )-selective HNLs have been isolated, usually from plant sources, where their natural substrates play a role in defense mechanisms of the plant through the release of HCN. In addition to there being HNLs with different stereo-preferences, two different classifications have been defined, based on whether the HNL contains a flavin adenine dinucleotide (FAD) co-factor. 

A stereospecific total synthesis of prostaglandins E3 and F3, containing an additional double bond in this side chain, starts from the optically active phosphonium salt 161. In this synthesis the ( )-13-double bond and the 15-hydroxy function are generated simultaneously by condensation of the chiral bicyclic aldehyde 163 with the P-oxido ylide 162 obtained by treatment of 161 with methyllithium. The corresponding phosphonium salt S) +)-161, already possessing the (Z)-configurated A17-double bond of prostaglandins, was prepared from (S)(—)-tartaric acid 1351 (Scheme 29). 

In addition to its stereoselectivity, the synthesis of chiral a-hydroxy aldehydes (69) from the aminal (68) has the advantage that the chiral auxiliary reagent (67) is easily prepared from (S)-proline, and that it may be recovered unchanged after use (79CL705). 

Af-(Phenylsulfanylmethyl)oxazolidinones derived from camphor 494 can be lithiated with n-BuLi at —78°C to give the chiral formyllithium equivalent 478683 (Scheme 128). This intermediate added to aldehydes in good yields, but lower stereoselectivity than compound 477, to afford crystalline adducts, which allowed the isolation of the major diastereomer 495. Hydrolysis of these adducts gave a-hydroxy aldehydes, which can be oxidized with PCC to the corresponding a-hydroxy acids. 

Chiral -hydroxy carboxylic acids. The enolate of 1, prepared by reaction with LDA followed by transmetallation with MgBr, reacts with aldehydes to provide the diastereomers 2 and 3 in the ratio 92-97 8-3. The adducts are cleaved by KOH in aqueous methanol to chiral (3-hydroxy carboxylic acids (4) and the chiral diol 5. 

Addition to a-hydroxy aldehydes. The Lewis acid-catalyzed addition of 1 to aldehydes to afford homoallylic alcohols (9, 8) has been extended to the reaction with derivatives of a chiral a-hydroxy aldehyde (2), which can result in the monoderivative of a jyn-diol (3) and/or an anti-d o (4). The diastereoselectivity can be controlled by the... 

Chiral tertiary u-hydroxy aldehydes This chiral 1,3-oxathiane (1) undergoes the highly selective reactions shown by 4,4,6-trimethyl-1,3-oxathiane (this volume) to give the optieally aetive oxathiane carbinols 3 in greater than 90% diastereomeric purity. These are cleaved by NCS antj silver nitrate (4, 216) to a-hydroxy aldehydes (4) and a sultine. which can be converted back to 1 (95% yield). The a-hydroxy aldehydes (4) are unstable... 

Chiral secondary a-hydroxy aldehydes, Rf HOHCHO. The chiral acyl derivatives 3, obtained from 1 by lithiation and reaction with an aldehyde followed by Swem oxidation, can be reduced stereoselectively before cleavage to the secondary a-hydroxy aldehydes. 

Diastereoselecttve aldol reactions. The diastereoselectivity in the Lewis acid-catalyzed aldol reaction of chiral oi-hydroxy aldehydes is independent of the geometry of the enol silyl ether. Also, the reaction does not involve prior Si-Ti or Si-Sn exchange. 

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