Aldehydes base-promoted

As an example of enolate-ion reactivity, aldehydes and ketones undergo base-promoted o halogenation. Even relatively weak bases such as hydroxide ion are effective for halogenation because it s not necessary to convert the ketone completely into its enolate ion. As soon as a small amount of enolate is generated, it reacts immediately with the halogen, removing it from the reaction and driving the equilibrium for further enolate ion formation. 

Leighton has combined this concept of strained silacycles [62-66] with the asymmetric allylation chemistry in a series of pubhcations [60, 67-70], Leighton s aUyhc silacyclopentane 29 [67] (Scheme 20) works equally for allylation of aromatic and ahphatic aldehydes in the absence of additional Lewis bases (promoter activator) or Lewis acids with high yield and enantioselectivity. The mechanism of... 

Denmark utilized chiral base promoted hypervalent silicon Lewis acids for several highly enantioselective carbon-carbon bond forming reactions [92-98]. In these reactions, a stoichiometric quantity of silicon tetrachloride as achiral weak Lewis acid component and only catalytic amount of chiral Lewis base were used. The chiral Lewis acid species desired for the transformations was generated in situ. The phosphoramide 35 catalyzed the cross aldolization of aromatic aldehydes as well as aliphatic aldehydes with a silyl ketene acetal (Scheme 26) [93] with good yield and high enantioselectivity and diastereoselectivity. 

Asymmetric aldol additions of geometrically defined trichlorosilyl enolates of ketones to aliphatic and aromatic aldehydes have been carried out uncatalysed, and with a chiral phosphoramide as Lewis base promoter.54 Significant differences in rates and diastereoselectivities are interpreted in terms of the changeover from a boat-like transition state, with pentacoordinate siliconate, to a chair-like transition state with hexacoordination. 

The Darzens reaction is the base-promoted generation of epoxides XIII from aldehydes (or ketones) XI and alkyl halides XII, the latter carrying an electron withdrawing group, for example the carbonyl, nitrile, or sulfonyl, in the a-position (Scheme 6.83) [188, 189]. It is, formally, addition of a carbene to the C=0 double bond (Scheme 6.83, path B) and thus complements oxygen atom transfer to olefins... 

Liu L, Ji L, Wei Y (2008) Base promoted aerobic oxidation of alcohols to corresponding aldehydes or ketones catalyzed by CuCl/TEMPO. Catal Commun 9(6) 1379-1382... 

Mechanism 22-6 Base-Promoted Halogenation 1054 Mechanism 22-7 Final Steps of the Haloform Reaction 1056 Mechanism 22-8 Acid-Catalyzed Alpha Halogenation 1058 22-6 Alpha Bromination of Acids The HVZ Reaction 1059 22-7 The Aldol Condensation of Ketones and Aldehydes 1060... 

Addition of an Enolate to Ketones and Aldehydes (a Condensation) 1046 Substitution of an Enolate on an Ester (a Condensation) 1046 Base-Catalyzed Keto-EnolTautomerism 1047 Acid-Catalyzed Keto-EnolTautomerism 1047 Base-Promoted Halogenation 1054 Final Steps of the Haloform Reaction 1056 Acid-Catalyzed Alpha Halogenation 1058 Acid-Catalyzed Aldol Condensation 1063 1,2-Addition and 1,4-Addition (Conjugate Addition) 1085... 

Synthetic thiazolium salts (86c), developed by Stetter and his co-workers and similar to thiamine itself (Stetter 1976), have been successfully used by Suzuki et al. for a diastereoselective intramolecular crossed aldehyde-ketone benzoin reaction in the course of an elegant synthesis of preanthraquinones (Hachisu et al. 2003). By using the highly functionalized isoxazole 104 as substrate, the tetracyclic a-hydroxy ketone 105 was obtained by base-promoted cyclocondensation in good yield. The high diastereoselectivity was induced by pre-existing stereocenters in the substrates (Scheme 28). 

Sulfur ylides, derived from benzyl bromides and an optically active alkyl sulfide, undergo base-promoted reactions with aryl aldehydes to produce optically active 1,2-diatyl epoxides.The reaction is illustrated by equation (17) and produces epoxides with optical purities in the range of 28-47% ee. The bicyclic sulfide shown in equation (17) was derived from (-t-)-camphor8ulfonic acid and produces the (RiO-enantiomer of the epoxide in excess. 

Pentacoordinate silicon, in the form of allyltrichlorosilane, in the presence of DMF or HMPA, also undergoes allylation with aldehyde [97,98], The Lewis base-promoted approach has the merit of operational convenience. Stereoselective formation of allylic trichlorosilanes is achieved by copper-catalyzed coupling of allylic chloride and trichlorosilane or by palladium-catalyzed hydrosilylation of 1,3-dienes (Sch. 56) [99],... 

Base-promoted reaction of nitrobenzenes 680 with aryl imines 681 afforded arylindazoles 682 (Equation 144) <20000L413>. /3-Tosylhydrazono phosphonates 683, novel and bifunctional reagents, were employed in a concise approach to give polysubstituted pyrazoles 684 in the presence of aromatic and aliphatic aldehydes under basic conditions (Equation 145) <1999SL299>. 

Base-promoted halogenation of aldehydes and ketones is little used ir, practice because it s difficult to stop the reaction at the monosubstituted product. An -halogenated ketone is generally more acidic than the star ing, unsubstituted ketone because of the electron-withdrawing inductiv effect of the halogen atom. Thus, monohaiogenated products are themselvi rapidly turned into enoiate ions and further halogcnated. 

Ketene acetals. Homologation with protection of aldehydes is accomplished by a base-promoted condensation with (Et0)2CHP(0)Phj and elimination of Ph2P(0)OH. If asymmetric dihydroxylation is then applied to the enol ethers, chiral ethyl a-hydroxyalkanoates are obtained. 

There are very few examples of Lewis base-promoted allylations of aldehydes with allylstannanes. In 1992 Baba disclosed an intriguing method for allylation of aldehydes with allyl- and 2-butenyltributylstannanes in the presence of catalytic-amounts of dibutyltin dichloride and certain coactivators such as tetrabutylammo-nium iodide, tributylphosphine oxide, HMPA or tetraphenylphosphonium iodide [76]. No definitive mechanistic information is available on the role of the co-activators the authors speculate that the ligands accelerate the metathesis to form allyldibutyltin chloride which is the actual nucleophile. The same group has recently reported the use of a lead(II) iodide/HMPA catalyst for the allylation of a,yff-epoxyketones [76bj. 

Base-promoted isomerizations of oxiranes by way of oxirane C—H abstraction are less common. Lithium tetramethylpiperidide (LiTMP) has successfully been used for this purpose <94CC2103>. Monosubstituted oxiranes are isomerized with LiTMP to aldehydes. 

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