Intramolecular reactions acyloin

Another important reductive coupling is the conversion of esters to a-hydroxyketones (acyloin condensation).267 This reaction is usually carried out with sodium metal in an inert solvent. Good results have also been obtained for sodium metal dispersed on solid supports.268 Diesters undergo intramolecular reactions and this is also an important method for the preparation of medium and large carbocyclic rings. 

The acyloin condensation converts two esters to an cr-hydroxyketone (an acy-loin), often in an intramolecular fashion. The reaction proceeds by a mechanism very similar to the pinacol coupling, except that after the radical-radical combination step there are two elimination steps and two more electron transfer steps. The intramolecular reaction works well for a wide variety of ring sizes. 

The acyloin condensation involves essentially the same chemistry as the pinacol reaction, but the substrates are esters, rather than aldehydes or ketones, and most reactions use an alkali metal as the electron source (Figure 20.10) 4 moles of sodium are needed to complete the reaction. The reaction is often modified by addition of trimethylchlorosilane, to capture the dianion. This is called the Riihlman modification and allows the reaction to proceed successfully for intramolecular reactions giving rise to both small and medium rings, mainly by suppressing potential side reactions. Examples are shown in Figure 20.11. 

The intramolecular condensation reaction of diesters, the Dieckmann condensation, works best for the formation of 5- to 7-membered rings larger rings are formed with low yields, and the acyloin condensation may then be a faster competitive reaction. With non-symmetric diesters two different products can be formed. The desired product may be obtained regioselectively by a modified procedure using a solid support—e.g with a polystyrene 10 ... 

Alkyl alkanoates are reduced only at very negative potentials so that preparative scale experiments at mercury or lead cathodes are not successful. Phenyl alkanoates afford 30-36% yields of the alkan-l-ol under acid conditions [148]. Preparative scale reduction of methyl alkanoates is best achieved at a magnesium cathode in tetrahydrofuran containing tm-butanol as proton donor. The reaction is carried out in an undivided cell with a sacrificial magnesium anode and affords the alkan-l-ol in good yields [151]. In the absence of a proton donor and in the presence of chlorotrimethylsilane, acyloin derivatives 30 arc formed in a process related to the acyloin condensation of esters using sodium in xylene [152], Radical-anions formed initially can be trapped by intramolecular addition to an alkene function in substrates such as 31 to give aiicyclic products [151]. 

Acyloins undergo nucleophilic addition to /3-ethoxyvinylphosphonium salts (141) to yield an ylide (142) (74JOC584). Intramolecular Wittig reaction results in formation of the dihydrofuran (143), which is converted to the furan (144) by elimination of ethanol (Scheme 32). Symmetric acyloins give one product, but unsymmetrical ones may give two products under basic conditions due to tautomerization. 

A modification involves the addition to the reaction mixture of chlorotrimethyl-silane which gives the bis-(trimethylsilyloxy)alkene which is hydrolysed to yield the acyloin.145 A preparative example, which also illustrates an intramolecular acyloin reaction to form an alicyclic ring system, is given in Expt 7.10. 

The bimolecular reductive coupling of carboxylic esters by reaction with metallic sodium in an inert solvent under reflux gives an a-hydroxyketone, which is known as an acyloin. This reaction is favoured when R is an alkyl. With longer alkyl chains, higher boiling solvents can be used. The intramolecular version of this reaction has been used extensively to close rings of different sizes, e.g. paracyclophanes or catenanes. 

One typical radical reaction is a coupling reaction. Oxidative decarboxylation coupling reaction of carboxylic acids by electrolysis (Kolbe electrolysis), intramolecular coupling reaction of diesters with Na (acyloin condensation), formation of pinacols from ketones or aldehydes with Na or Mg are well known classical methods [1,2]. Recently, oxidative... 

A closely allied reductive linking of carbonyl groups is an intramolecular version with esters, called the acyloin reaction, which again gives a 1, 2-dioxygenated skeleton... 

The asymmetric intramolecular benzoin condensation with model substrate 106 (R = Me) and the chiral triazolium salt 119 as precatalyst gave rise to the desired acyloin 107 in good yields by utilizing toluene as solvent and diazabicycloundecane (DBU) or KOt-Bu as the base (Scheme 33). Unfortunately only moderate enantiomeric excess (37% 18%) could be achieved, even at 5°C. The use of 10 mol% of the TBS-substituted catalyst 123 and stoichiometric amounts of DBU in toluene at room temperature enabled the methyl-substituted acyloin 106 to be obtained in high yield (92%) but with only moderate enantios-electivity (61%). Application of the TIPS substituted catalyst 123 under the same conditions resulted in an increased enantiomeric excess of 77%, which could be further improved to 84% with almost unchanged yields by performing the reaction at 5°C. The reactions with the tetracyclic catalyst 127 were conducted in tetrahydrofuran for better solubility. Furthermore, DBU was found to cause side-reactions that could be suppressed when KOf-Bu was used in substoichiometric amounts (9... 

An intramolecular reductive coupling of ketones with nitriles has been reported for acyclic and monocyclic substrates y9-amino nitriles were isolated from acyclic malononitrile adducts [87]. The Sml2-initiated reductive cyclization of cyclic a-cyanoalkyl-substituted ketones leads to acyloin products in high yields. In this instance further irradiation of the reaction mixtures was performed to afford complete conversion (Scheme 27) [88]. More applications have been collected in several excellent reviews [89-92]. 

From a synthetic point of view, bond forming steps are the most important reactions of radical ions [202]. Several principle possibilities have been described in Section 8.1 and are summarized in Scheme 52. Many carbo- and heterocyclic ring systems can be constructed by (inter- and intramolecular) radical addition to alkenes, alkynes, or arenes. Coupling of carbonyl radical anions leads to pinacols either intra-or inter-molecular which can be further modified to give 1,2-diols, acyloins or alkenes. Radical combination reactions with alkyl radicals afford the opportunity to synthesize macrocyclic rings. These radical ion-radical pairs can be generated most efficiently by inter- or intramolecular photoinduced electron transfer. 

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