Diastereoselectivity aldols

Diastereoselective Aldol Condensation with Boron Enolates... 

The a-alkoxy iron-acyl complex 5 may be deprotonated to generate the lithium enolate 6, which undergoes a highly diastereoselective aldol reaction with acetone to generate the adduct 7 as the major product. Deprotonation of acetone by 6 is believed to be a competing reaction 30% of the starting complex 5 is found in the product mixture48 40. 

The boron enolates derived from (5)-4-silylated 2,2-dimethyl-l,3-dioxan-5-one undergo anti diastereoselective aldol reactions which provide access to protected oxopolyols of high stereochemical integrity <96SYN1095>. 

Scheme 37 Asymmetric synthesis of 1,2-diamines from chiral a-aminonitriles derived from diastereoselective aldolization...

A jy -diastereoselective aldol reaction based on titanium enolates from (A)-l-benzyloxy-2-methyl-3-pentanone was developed by Solsona et al. (Equation (12)).64 The titanium enolate of this chiral ketone afforded the corresponding syn-syn aldol adducts in high yields and diastereomeric ratios with a broad range of aldehydes. 

Finally, several diastereoselective aldol reactions using titanium enolates and carbonyl electrophiles have also been applied to the total synthesis of natural products.69-72... 

TABLE 3-1. Diastereoselective Aldol Reaction Using Chiral Reagent 5... 

Scheme 4.37. Diastereoselective aldol reactions of an alkyl zirconocene.

Diastereoselective aldol condensations.1 The aldol condensation of a chiral ethyl ketone such as 2 with aldehydes catalyzed by Bu2BOTf gives a mixture of all four possible diastereomeric adducts with little or no stereocontrol. In contrast, reactions catalyzed by either (+)- or (- )-l are highly diastereoselective. By proper choice of (+)- and (- )-l and of (+)- and (- )-2, each one of the four possible 1,2-yyn-diastereomers can be obtained in high purity. 

Diastereoselective aldol reactions The boryl enolates of chiral crotonate imides (1) and (2) react with aldehydes to form adducts (3) and (4), respectively, with high diastereoselectivity and complete a-regioselectivity. The method of choice for reductive cleavage of the adducts is formulated for 3 hydrolysis can also be effected with LiOH and H202. 

Diastereoselective aldol condensations. This furan (1) can undergo condensation with aldehydes as a butenolide to form 8-hydroxy-a,(3-unsaturated--y-lactones (2). The diastereoselectivity can be controlled by the choice of catalyst. Lewis... 

Scheme 9 EGA-catalyzed diastereoselective aldol reaction of acetal with an enolether.

Diastereoselective aldol condensations and related reactions. The geometry of enolates... 

The utilization of a-amino acids and their derived 6-araino alcohols in asymmetric synthesis has been extensive. A number of procedures have been reported for the reduction of a variety of amino acid derivatives however, the direct reduction of a-am1no acids with borane has proven to be exceptionally convenient for laboratory-scale reactions. These reductions characteristically proceed in high yield with no perceptible racemization. The resulting p-amino alcohols can, in turn, be transformed into oxazolidinones, which have proven to be versatile chiral auxiliaries. Besides the highly diastereoselective aldol addition reactions, enolates of N-acyl oxazolidinones have been used in conjunction with asymmetric alkylations, halogenations, hydroxylations, acylations, and azide transfer processes, all of which proceed with excellent levels of stereoselectivity. 

DIASTEREOSELECTIVE ALDOL CONDENSATION USING A CHIRAL OXA2DLIOINONE AUXILIARY (2S, 3S )-3-HYDR0XY-3-PHENYL-2-METHYLPR0PAN0IC ACID... 

Scheme 6.32 y-Butenolides obtained from diastereoselective aldol addition of 2-trimethylsilyloxyfuran to aldehydes catalyzed by urea 32. 

Some enantiomerically pure substituted 2-oxazolidinones are excellent as chiral auxiliaries. From the pioneering studies 2 conducted in the early 1980 s of the uses of such auxiliaries has emerged what is perhaps the most widely used method today for the preparation of enantiomerically highly enriched a-alkylalkanoic acids, alcohols and aldehydes, that is, the alkylation of enolates from chiral 3-acylated 2-oxazolidinones followed by auxiliary removal2 59. The early work has been reviewed60-62. These enantiomerically pure cyclic imide auxiliaries have been used not only for alkylations but also in a plethora of a-functionalization reactions, such as diastereoselective aldol, a-hydroxylation, a-amination and Diels-Alder reactions and these are discussed elsewhere in this volume. 

With meso-conflgured dialdehyde precursors, the enantiotopic nature of the termini must give rise to a conflgurational terminus differentiation upon twofold chain extension because the catalyst-controlled diastereoselective aldol additions will break the inherent o symmetry. While the two enantiotopic termini cannot... 

TABLE 6. Diastereoselective aldol-type reaction of bislactim ether with aldehydes... 

The oxazolidinones have been used as chiral auxiharies for enolate alkylation and aldol reactions in enantioselective and total syntheses The interest in these substrates is largely known for iyw-diastereoselective aldol reactions with chlorotitanium or diaUcylboron oxazilidinone enolates (equation 114). 

Having identified the (+)-stereoisomer as the biologically active isomer, several independent enantioselective syntheses of this stereoisomer were developed. The initial synthesis developed in discovery chemistry employed the diastereoselective aldol condensation pioneered by Braun as the key component. Thus, treatment of aldehyde 13 from the racemic synthesis with the magnesium enolate of (5)-(+)-2-acetoxy-l,l,2-triphenylethanol at -70 °C, afforded 17 in 60% yield as a 97 3 mixture of the / ,5 5,5-diastereomers by HPLC (Scheme 3). Ester exchange employing sodium methoxide provided the methyl ester in quantitative yield. Reaction of this ester with three equivalents of lithio-f-butylacetate at -40 °C afforded the nearly enantiomerically pure r-butyl ester analog of racemic 14 in 75% yield. 

These highly diastereoselective aldol reactions have been used in a synthesis of 6-deoxyerythronolide B (5), which contains 10 asymmetric centers. Four aldol reactions, indicated by dotted lines, were used to construct the carhon framework with overall stereoselection of 85%.2... 

To connect the C2 and C3 atoms of the 1-hydroxyethylene moiety, Wuts et al.[341 and Poss and Reid 35 used the Wadsworth-Emmons reaction between a (3-amino-a-hydroxy-aldehyde and a phosphonate (two-carbon fragment) to give the desired isostere after reduction of the alkene. In the synthesis reported by Poss and Reid (Scheme 17) the stereochemistry of the hydroxyl group at C4 is established by a highly diastereoselective aldol addition to furan. A slight modification was employed by Chakravarty et all36 and Plata et al.[37 where 4-amino-3-oxo phosphonates were reacted with an aldehyde or ketone form of the two-carbon fragment. 

Other examples of the uses of enolate derivatives of thioesters highly diastereoselective aldol reactions were reported by Gennari [3 and Hanaoka et al. [374, 375]. The latter reported the reaction between chromium-complexed benzaldehyde (1) and the titanium enolate of thioester (2) as the first step of sequences directed towards the synthesis (+)-goniofufurone [374] and the taxol C13 side-chain [375]. They also u cobalt-complexed acetylenic aldehydes for the selective formation of sy aldols [376]. 

Acyl-l,3-oxazolidine-2-thiones, chiral (1). Nagao and co-workers1 have prepared the chiral 3-acetyl-l,3-oxazolidine-2-thiones (la and lb) and used them to effect diastereoselective aldol reactions. The two chiral auxiliaries show, as expected, opposite diastereoselectivities, but contrast with the diastereoselectivities observed with chiral 4-alkyl-2-oxazolidones (11, 379-381). This aldol reaction has been used to prepare the chiral azetidinone 4 (equation I) and (-I- )-Prelog-Djerassi lactone. 

Diastereoselective aldol condensations.1 The reaction of (S)-( - )-2-benzyl-oxyhexanal (2) complexed with TiCl4 with the bistrimethylsilyl enol ether (1) of methyl acetoacetate gives almost exclusively the syn-aldol adduct (3). This reaction... 

Diastereoselective aldol reaction. Alkyl trityl ketones (2) are readily prepared by reaction of 1 with an aldehyde followed by Cr03 oxidation (50-70% overall yield). Because of steric effects these ketones undergo highly diastereoselective aldol condensation to give syn-adducts (95-99% syn). After protection of the hydroxyl group, the adduct is cleaved by lithium triethylborohydride.1... 

To address limitations in the use of glyceraldehyde acetonide (43) as a three-carbon chiral building block, butane-2,3-diacetal-protected glyceraldehyde (44, R1 = R2 = H) has been prepared. It undergoes diastereoselective aldol reactions with a range of carbonyl compounds esters, thioesters, and ketones. The work has been extended (g) to other derivatives such as the a-substituted aldehyde (44, R1 = Me, allyl) and the methyl ketone (44, R2 = Me).122a,b... 

A highly diastereoselective aldol of an a-CF3-substituted enolate has opened up a (g) new route to trifluoromethyl-substituted chiral centres.123... 

Diastereoselective aldol reactions. Heathcock and Flippin6 have observed that BF3 etherate can improve syn-selectivity in the reaction of an enolate (1) of pinaco-lone with 2-phenylpropanal (equation I). Thus, the reaction of the t-butyldimethylsi-lyl enolate in the presence of BF3 etherate is more syn-selective than that of the... 

Amino-y-butyrolactones.5 The (dimethylamino)carbene 1 undergoes highly diastereoselective aldol reactions with aldehydes even in the absence of a Lewis acid to form syn-adducts 2, from which the metal unit can be removed by photolysis. 

Diastereoselective aldol coupling of alkynyl aldehydes.3 The Co2(CO)6 complexes (2) of alkynyl aldehydes react with silyl enol ethers to form aldols with... 

P-Hydroxy carboxylic acids (12,3).2 This acetate on double deprotonation with LDA undergoes diastereoselective aldol reactions with aldehydes. The adducts are easily hydrolyzed to optically active P-hydroxycarboxylic acids with release of (R)-(+)-1,1,2-triphenyl-1,2-ethanediol, the precursor to 1. Optically pure acids can be obtained by crystallization of the salt with an optically active amine such as (S)-(—)-1 -pheny lethylamine. 

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