Aldehydes cross-coupling with

Electrophiles also react at C-5 of 1,3-dioxin-4-ones. Two ways of activation have been reported (1) magnesiation of 5-iodo-l,3-dioxin-4-ones afforded the Grignard reagents which can be cross-coupled with allyl halides in the presence of copper cyanide <2001TL6847> or with iodoalkenes under Pd(0) catalysis <2002T4787> and (2) Sc(OTf)3-catalyzed reaction of a side-chain-hydroxylated l,3-dioxin-4-one with aldehydes provided the bicyclic dioxinone in 60-85% yield (Scheme 27) <20050L1113>. 

The anion derived from the 1,3-dithiole 367 reacts with thioxanthone to give the 9-(l,3-dithiol-2-ylidene)thiox-anthene derivative which is a 7t-electron donor system. The introduction of a benzaldehyde unit at the 4-position of the dithiole ring was achieved by iodination and a Pd-mediated cross-coupling with 4-formylbenzeneboronic acid. The aldehyde group allowed attachment to C(,o via a 1,3-dipolar cycloaddition of an azomethine ylide (Scheme 87) <2005JMC1232>. 

The Reformatsky reagents, i.e. zinc enolates of esters, undergo Ni catalysed cross-coupling with aryl halides.53 The Ni catalysed reaction of arylzincs with a-bromoacetates also permits a-arylation of esters54 (Scheme 11.13). However, a-alkenylation of enolates of ketones, aldehydes, and esters has been less satisfactory. Its further development is clearly desirable. Alternatively, a-alkenylation of a-iodoenones in conjunction with conjugate reduction discussed earlier should be considered. 

The insight that zinc ester enolates can be prepared prior to the addition of the electrophile has largely expanded the scope of the Reformatsky reaction.1-3 Substrates such as azomethines that quaternize in the presence of a-halo-esters do react without incident under these two-step conditions.23 The same holds true for acyl halides which readily decompose on exposure to zinc dust, but react properly with preformed zinc ester enolates in the presence of catalytic amounts of Pd(0) complexes.24 Alkylations of Reformatsky reagents are usually difficult to achieve and proceed only with the most reactive agents such as methyl iodide or benzyl halides.25 However, zinc ester enolates can be cross-coupled with aryl- and alkenyl halides or -triflates, respectively, in the presence of transition metal catalysts in a Negishi-type reaction.26 Table 14.2 compiles a few selected examples of Reformatsky reactions with electrophiles other than aldehydes or ketones.27... 

Aromatic aldehydes, Ar CHO, have been cross coupled with diarylbromomethanes, Ar Ar CHBr, to give diaryl acetophenone derivatives, Ar COCHAr Ar, using NHC catalysis. A benzoin can be used as a masked aldehyde in the reaction, indicating that the formation of the Breslow intermediate is reversible. The utility of the reaction has been extended on the halide side a-halo ketones and esters can serve in place of diarylmethyl bromides. 

TMS-alkynes are oxidized at the terminal carbon to carboxylic acids by hydroboration/oxidation (dicyclohexylborane/NaOH, H2O2). This does not work with TIPS-alkynes. Instead, TIPS-alkynes are cleanly monohydroborated at the internal carbon by 9-borabicyclo[3.3.1]nonane dimer to give (Z)- -borylvinyl-silanes. These can be oxidized in high yields to a-silyl ketones, or cross coupled with a bromide R Br (R = aryl, benzyl, dimethyl-vinyl) in the presence of NaOH and tetrakis(triphenylphos-phine)palladium(0) to give /3,/3-disubstituted vinylsilanes (Suzuki reaction eq 14). The same nucleophilic substituted vinylsilane can be added to an aromatic aldehyde to provide access to ( )-3-silyl allyl alcohols. ... 

Good functional group tolerance was observed halides, esters, aldehydes, and vinyl and nitro groups were all viable substituents. Benzothiazoles can also undergo Cu-catalyzed dehydrogenative cross-coupling with silver(I) as an oxidant (eq 43). ... 

In a cross-coupling benzoin condensation of two different aldehydes, usually a mixture of products is obtained, with the ratio being determined by the relative stabilities of the four possible coupling products under thermodynamic control. If, however, an acyl silane, e.g. 5, is used as the donor component, the a-silyloxy-ketone 6 is obtained as a single product " ... 

Optically active (Z)-l-substituted-2-alkenylsilanes are also available by asymmetric cross coupling, and similarly react with aldehydes in the presence of titanium(IV) chloride by an SE process in which the electrophile attacks the allylsilane double bond unit with respect to the leaving silyl group to form ( )-s)vr-products. However the enantiomeric excesses of these (Z)-allylsilanes tend to be lower than those of their ( )-isomers, and their reactions with aldehydes tend to be less stereoselective with more of the (E)-anti products being obtained74. 

Trimethyl(l-phenyl-2-propenyl)silane of high enantiomeric excess has also been prepared by asymmetric cross coupling, and reacts with aldehydes to give optically active products in the presence of titanium(IV) chloride. The stereoselectivity of these reactions is consistent with the antiperiplanar process previously outlined75. 

Even with the limitation on yield implied by the statistical process, cross-dimerization is still useful when one of the reactants is an alkane, because the products are easy to separate, and because of the few other ways to functionalize an alkane. The cross-coupling of an alkane with trioxane is especially valuable, because hydrolysis of the product (10-6) gives an aldehyde, thus achieving the conversion RH RCHO. The mechanism probably involves abstraction of H by the excited Hg atom, and coupling of the resulting radicals. 

A cross-coupling reaction of aldehydes with a-diketones proceeded in the presence of water to give the corresponding adducts in moderate to good yield. It is possible to use the substrates such as phenyl-glyoxal monohydrate, aqueous methylglyoxal, formalin, and aqueous a-chloroacetaldehyde for this reaction.330... 

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