Ketones intermolecular coupling

The 1,5- and 1,6-dialdehydes 22 and 24 undergo the annulative pinacol coupling to give the cyclic vzc-diols 23 and 25, respectively (Scheme 13) [29]. The vanadium-catalyzed intramolecular coupling reaction of 1,5-diketone 26 also proceeds with excellent selectivity (Scheme 14) although the intermolecular coupling of ketones such as acetophenone results in low diastereoselectivity under these conditions [21]. 

In contrast to the high regioselectivity and good yields of electroreductive intramolecular coupling reactions of ketones with multiple bonds shown in Schemes 34 to 37, the yields of interm olecular coupling reactions have been very low until recently. However, by using carbon fiber electrodes, intermolecular coupling reactions have... 

Scheme 38 Cathodic intermolecular coupling of ketones with alkenes R R, R alkyl, yield 52-82%.

Scheme 40 Cathodic intermolecular coupling of ketones with vinyl trimethylsilane R R alkyl, R prim. sec. alcohol, yields 35-96%.

The existence of a trimethylsilyl group on the carbon-carbon double bond seems to activate the double bond towards radical addition since the electroreductive intermolecular coupling of ketones with carbon-carbon double bond predominantly takes place at the... 

Electroreduction of y- and 5-cyano ketones in isoPrOH with a Sn cathode gave a-hydroxyketones with good diastereo-selectivities as cyclization products. The reaction has been used as a key step for the synthesis of, for example, guaiazulene, triquinanes, and dihydrojasmone. Similarly, the corresponding intermolecular couplings were realized [315]. 

Intermolecular coupling between ketones and 0-methyl oximes, hydrazones and nitrones is achieved on reduction at a tin cathode in isopropanol [105]. It is not clear which of the reacting species accepts the initial electron in these processes. The reaction with 0-methyloximes, followed by catalytic reduction of the first formed O-methylhydroxylamine, is a convenient synthetic route to 2-amino-alcohols. 

It is quite interesting that cathodic intra- and intermolecular coupling of a ketone with a vinylsilane (equations 97 and 98) takes place by using a carbon fiber cathode121. The carbon fiber cathode is essential for these reactions. 

Intermolecular coupling of ketones and alkenes, promoted by SmH, occurs with excellent stereochemical control. In one such reaction, samarium(II) iodide has been used to prepare cyclobutanones and cyclobutanols from chiral, 6-oxohex-2-enoates (equation 137)520. The reaction is performed in THF in the presence of HMPT and occurs in good yield with excellent stereocontrol. If appropriately located carbonyl and alkene moieties are present in a molecule, then Sml2-HMPT can be used to form cyclooctanols by a radical cyclization process in some cases there is a reasonable degree of diastereoselectivity (equation 138)521,522. 

The intermolecular coupling of homoallyl alcohols with o-bromoacetophenone 127 (Scheme 3-33) or o-bromostyryl ketones 129 (Scheme 3-34) gave dihydro- 128 and tetrahydronaphtlialene derivatives 130 in a sequence of Heck and aldol or Heck and Michael reactions [185]. After addition of the arylpalladium species formed initially... 

Intermolecular coupling of pyridines with ketones under acidic conditions has received attention but like the intramolecular reductive coupling of aromatic rings linked to aliphatic ketones [Eq. (62)], the reaction is essentially a ketone reduction, and the reader is referred to Chapter 10. 

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... 

Matsuda et al. have studied the hydroxyl group directed intermolecular ketone-olefin coupling reactions, induced by Sml2, between a-hydroxy ketones and a,P-unsaturated esters or nitriles (Scheme 30). It was noted that reactions... 

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. 

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. 

Shono and coworkers achieved electroreductive intra- and intermolecular couplings of ketones and nitriles in 2-propanol solutions containing Et4NTos using Sn cathodes at controlled potential (-2.8 V SCE). Intramolecular coupling of cyclic y- and (5-cyano ketones, besides good to excellent yields, proved to be cis stereoselective when a-hydroxy ketones with bicyclo[3.3.0] or [4.3.0] skeletons were formed. When the reactions were carried out at 65 °C instead of 25 °C, dehydration of hydroxy ketones occurred and the corresponding a,jS-unsaturated ketones were obtained. The presence of alkyl or 2-ethoxycarbonyl substituents did not hinder the cyclization. In Table 13 some representative examples are shown. 

Attempted intermolecular coupling of ketones and nitriles under conditions similar to those used for intramolecular coupling led to mixtures of two types of ketone-nitrile coupling products and alcohols resulting from ketone electroreduction. Product selectivity could be changed altering nitrile/solvent (2-propanol or ethanol) composition. Some results for cyclohexanone/acetonitrile reductions are shown in Scheme 27. 

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. ... 

Demir et have reported the first, catalytic, intermolecular aldehyde-ketone (103) coupling with acyl phosphonate (102). The cyanide ion catalyzed formation of acyl anion from acyl phosphonates, which next reacted with activated carbonyl compounds to furnish products (104) in 41-95% yields after phosphorylation of the resulting oxyanion (Scheme 23). 

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