Intermolecular Coupling of Aldehydes and Ketones

1 and 6.2 Table 6.1). The driving force of the reaction is the formation of strong titanium-oxygen bonds. 

Product TiCI, Reducing Agent Solvent Yield [%) Ref. 

7 kcal respectively [14, 15], and it has been estimated that olefins with a 

---

Samarium diiodide-induced intermolecular coupling of aldehydes and ketones to indoles with an electron-withdrawing group at the 3-position of the indole have also been reported [19]. Carbonyl compounds including acetone, acetophenone, benzophenone, pivaldehyde, and isobutyraldehyde added to the C-2 position of the indole to give the thermodynamically stable trani-dihydroindole derivatives 27. 

Pinucolic coupling of ketones and aldehydes. The reaction of TiCU and 70 -80 mesh magnesium amalgamated with HgCIa leads to a Ti(H) species that is effective for intermolecular coupling of aldehydes and ketones as shown in the examples. ... 

The intermolecular coupling of aldehydes and ketones has been used to prepare unusual molecules, in particular sterically hindered and/or strained alkenes that exhibit specific physico-chemical properties and are of theoretical interest (Figures... 

Intermolecular Coupling of Aldehydes and Ketones with Functional Heteroatom Croups... 

Procter reported a solid-phase variant of Fukuzawa s asymmetric y-butyr-olactone synthesis (see Chapter 5, Section 5.2) that involves the intermolecular reductive coupling of aldehydes and ketones with a,p-unsaturated esters, immobilised using an ephedrine chiral resin 12.44 For example, treatment of acrylate 13 and crotonate 14 with cyclohexanecarboxaldehyde, employing Sml2 in THF, with tert-butanol as a proton source, gave lactones 15 and 16, respectively, in moderate yield and good to high enantiomeric excess (Scheme 7.11).44 The ephedrine resin 12 can be conveniently recovered and recycled.45... 

Samarium diiodide has also been used for the intramolecular coupling of aldehydes and ketones with O-benzyl formaldoxime [83], for the corresponding intermolecular coupling with diphenylhydrazone [84,85] and for the intramolecular coupling of an a,p-unsaturated ester with an oxime ether [86] (Scheme 39). In all these cases the addition of HMPA was found to be essential for a successful reaction. 

McMurry reactions will be presented in the following order intermolecular, intramolecular, mixed (tandem) couplings of aldehydes and ketones, and finally keto ester, oxoamide, and acetal couplings. All the compounds which serve as illustrations are listed in Tables 6.1-6.10, along with the titanium reagents and solvents used for their preparation and the yields of isolated products where not specified, the reactions were performed at solvent reflux temperature. 

The intermolecular Sml2 Reformatsky reactions of a-haloamides have similarly received little attention however, Ohta showed that 7V,tV-dibenzyl-a-haloamides undergo efficient coupling with a range of aldehydes and ketones (Scheme 5.94).148... 

Several contributions have appeared in which intermolecular reductive couplings between ketones or aldehydes and electron-deficient alkenes have been described [30h, 53]. Reactions of aldehydes and ketones with unsaturated esters result in the formation of lactones. Diastereoselectivities are normally modest in these cases, but can be quite high for certain substitution patterns (Eq. 45). 

Sml2 can effectively promote the intermolecular reductive dimerisation of aldehydes or ketones giving rise to symmetrical diols.7 9 Generally, arylalde-hydes and aryl ketones couple within seconds in THF at room temperature. Aliphatic aldehydes and ketones react considerably more slowly several hours are required for the aldehydes, whereas for ketones reaction times of 24 h are usually needed. Nevertheless, these slower couplings can be greatly accelerated by the addition of additives such as HMPA.10... 

Some diversity among the carbonyl components of the reaction has also been examined in the intermolecular reactions. For example, two groups have reported that the reaction of Cr(CO)3-complexed aryl aldehydes and ketones with oi,f -unsaturated esters leads to diastereomerically pure lactones, with radical coupling directed anti to the metal tricarbonyl center (Eq. 52) [60]. 

Few examples of what might be described as an intermolecular coupling reaction on inactivated alkenes has appeared [62], Thus ketyl radicals generated from aromatic aldehydes and ketones underwent intermolecular addition to the para position of another aldehyde. Cross-coupling reactions are not feasible in these systems and typically yields are quite low. 

Yu T, Sun X, Wang C et al (2005) Zirconocene-mediated intermolecular coupling of si-tethered diynes with alkynes ketones aldehydes and isocyanates by means of novel skeletal rearrangement of zirconacyclobutene-silacyclobutene and zirconacyclohexadiene-silacyclo-butene fused-ring intermediates. Chem Eur J 11 1895-1902... 

Arylative or silylative cyclizations of allenyl aldehydes or ketones have been reported (Equations (101) and (102)).459,459a The intermolecular process, that is, three-component coupling reaction of aldehydes, allenes, and arylboronic acids, is catalyzed by palladium as well (Equation (103)).46O 46Oa These reactions are proposed to proceed through nucleophilic attack of the allylpalladium intermediates to the carbonyl groups. 

Niobium. Szymoniak has developed a niobium-based method for the pinacol coupling of aliphatic aldehydes, aromatic aldehydes, and aromatic ketones (Eq. 3.18) [37]. In the presence of NbCl3, intermolecular couplings proceed with consistently high diastereoselectivity. In many cases, the diol forms an acetal with the remaining aldehyde, and this is isolated at the end of the reaction. The stereoselection of... 

Alkenes can be obtained from aldehydes or ketones on reductive dimerization by treatment with a reagent prepared from titanium(III) chloride and zinc-copper couple (or L1A1H4), or with a species of active titanium metal formed by reduction of titanium(III) chloride with potassium or lithium metal. This McMurry coupling reaction is of wide application, but in intermolecular reactions generally affords a mixture of the E- and Z-alkenes (2.99). 

---