Selective aldolization

Titanium tetrakis(diethylamide) selectively adds to aldehydes in the presence of ketones and to the least hindered ketone in compounds containing more than one ketone. The protection is in situ, which thus avoids the usual protection-deprotec-tion sequence. Selective aldol and Grignard additions are readily performed employing this protection methodology. ... 

Given the relatively rare appearance of oxetanes in natural products, the more powerful functionality of the Patemo-Biichi reaction is the ability to set the relative stereochemistry of multiple centers by cracking or otherwise derivitizing the oxetane ring. Schreiber noted that Patemo—Btlchi reactions of furans with aldehydes followed by acidic hydrolysis generated product 37, tantamount to a threo selective Aldol reaction. This process is referred to as photochemical Aldolization . Schreiber uses this selectivity to establish the absolute stereochemistry of the fused tetrahydrofuran core 44 of the natural product asteltoxin. ... 

Several chiral heterocyclic borylating agents have been found useful for enantio-selective aldol additions. The diazaborolidine 14 is an example.136... 

Various other examples of, sy -diastereoselective 60-67 or non-selective aldol reactions of titanium enolates with carbonyl electrophiles have been described.68... 

A highly diastereofacial /7-selective aldol reaction by using ester derivatives of norephedrine as a chiral auxiliary has been recently reported by Kurosu and Lorca (Scheme 38).138 This practical and general method proceeds via initial ( )-selective substrate enolization and provides access to a broad range of optically active 2-alkyl-3-hydroxycarboxylic acid esters of type 91. 

Using a similar C12,C 13 disconnection approach, Schinzer et al. also achieved a total synthesis of epothilone A (4) [16]. The key step involved a highly selective aldol reaction between ketone 27 and aldehyde 10 to afford exclusively alcohol 28 with the correct C6,C7 stereochemistry (Scheme 6). Further elaboration led to triene 29, which underwent RCM using ruthenium initiator 3 in dichloromethane at 25°C, to afford macrocyles 30 in high yield (94%). Although no selectivity was observed (Z E=1 1), deprotection and epoxidation of the desired Z-isomer (30a) completed the total synthesis [16]. 

Among chiral auxiliaries, l,3-oxazolidine-2-thiones (OZTs) have attracted much interest for their various applications in different synthetic transformations.2 Such simple structures, directly related to far better known chiral oxazolidinones,11,12,57 have been explored in asymmetric Diels-Alder reactions and asymmetric alkylations, but mainly in condensation of their /V-acyl derivatives with aldehydes. Chiral OZTs have shown interesting characteristics in anti-selective aldol reactions58 or combined asymmetric addition. 

The same natural product was synthesized by Paterson et al. [45] who assembled the carbon skeleton of the macrolide from three larger subunits as well. Instead of the Evans-Metternich variant they used their boron-mediated antz-selective aldol strategy which relies as the Evans-Metternich aldol on stereo-induction from the a-chiral center and translates the E-enolate geometry, established due to the use of Cy2BCl, to the anti aldol product (Scheme 33). 

Regio-, Enantio-, and Diastereo-selective Aldol Reactions. 10... 

Ir-diphosphine complexes have been shown to catalyze a number of potentially interesting C—C coupling reactions [41]. Special mention should be made of the various transformations of alkynes (cycloaddition, isomerization, dimerization, alkynylation), selected aldol and carbonylation reactions, even though the synthetic potential of some of these reactions has not been explored. 

Typical starting materials, catalysts, and products of the enamine-catalyzed aldol reaction are summarized in Scheme 17. In proline-catalyzed aldol reactions, enantioselectivities are good to excellent with selected cyclic ketones, such as cyclohexanone and 4-thianone, but generally lower with acetone. Hindered aldehyde acceptors, such as isobutyraldehyde and pivalaldehyde, afford high enantioselectivities even with acetone. In general, the reactions are anti selective, but there are aheady a number of examples of syn selective enamine aldol processes [200, 201] (Schemes 17 and 18, see below). However, syn selective aldol reactions are still rare, especially with cychc ketones. 

The present procedure is a modification of that originally reported by the submitter and co-workers. This procedure is applicable to a large scale preparation of the title compound in high overall yield (-80%) without purification of the intermediates by chromatography. The title compound is reported to be a useful reagent for anf/-selective aldol reactions with dicyclohexylboron triflate and triethylamine as enolization reagents. ... 

Deprotonation of the A -acyl substituent of benzothiazines gives a nucleophile that reacts by deacylation with a second molecule of starting material (Equation 46) < 1980TL3001 >. Such anions also react with ketones in an erythro-selective aldol condensation (Equation 47) <1983TL3883>. The selectivity is due to the formation of a Z-enolate and the reaction was also extended to A -acylphenothiazines. 

Boron enolates bearing menthol-derived chiral ligands have been found to exhibit excellent diastereo- and enantio-control on reaction with aldehydes34 and imines.35 Highly diastereo- and enantio-selective aldol additions of geometrically defined trichlorosilyl ketone enolates (31) and (32) have been achieved by promoting the reactions with chiral Lewis bases, of which (,S., S )-(33) proved to be the most effective.36 Moderate enantiomeric excesses have been achieved by using chiral ammo alcohols as catalysts for the Baylis-Hillman condensation of aldehydes with methyl vinyl ketone the unexpected pressure effect on the reaction has been rationalized.37... 

Examples of highly enantio- and regio-selective aldol condensation reactions have featured in a review of organic synthesis and catalytic antibodies.188... 

This work raises the possibility that some eryfAro-selective aldol condensations with metal enolates may actually involve the a-metallo ketone. 

In contrast, acyclic intermediates (5 and 6) have been isolated in the reaction of 1 with C6H5CHO in the presence of BF, etherate. Evidently this cycloaddition operates through a rAreo-selective aldol-type process. 

A catalytic enantio- and diastereo-selective aldol reaction of ketones with ketene (g) silyl acetals, H2C=C(OTMS)-OMe, gives fair to good yields and ee.129 With further substitution of the vinyl function, the reaction is diastereoselective, up to 97%. A highly developed catalyst/promoter protocol is employed a copper fluoride complex is combined with a Taniaphos auxiliary (a chiral ferrocenyldiphosphine), plus (EtO)3SiF. Evidence for the formation of species (EtO)4 SiF (n > 2) as active... 

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