Acyloin condensation intramolecular

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 ... 

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. 

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]. 

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... 

Intramolecular acyloin condensation [71] of the diester 90 under dilution conditions with sodium in toluene and with addition of trimethylsilyl chloride led to the bis(trimethylsilyl)en-diol ether 91 (29% yield) which was transformed subsequently in several steps to [l.l.l.ljparacyclophane 92 [71a]. 

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. 

Modem acyloin condensations are usually executed in the presence of Me3SiCl, and a bis(silyloxy)alkene is obtained as the immediate product. The bis(silyl-oxy)alkene may then be hydrolyzed to the acyloin upon workup. The yield of the acyloin condensation is greatly improved under these conditions, especially for intramolecular cyclizations. The MesSiCl may improve the yield by reacting with the ketyl to give a neutral radical, which can undergo radical-radical combination more easily with another ketyl radical due to a lack of electrostatic repulsion. 

Acyloin condensation. Carbene species (for promoting intramolecular acyloin condensation) are mote readily generated from 1,2,4-triazolium salts when one of the iV-substituents is highly electron-deficient (e.g., 1). The bicychc triazolium salt 2 derived... 

The acylation of a-alkoxylithium reagents, prepared by the transmetallation of the corresponding stannanes,with a tertiary amide, provides an interesting and flexible approach to acyloin products. Intramolecular condensations are also possible allowing the preparation of small and normal ring ketones [equation (31)]. ... 

Scheme 9.146. A representation of an intramolecular Claisen-type condensation (an acyloin condensation) in which the diethyl ester of 1,6-hexanedicarboxylic acid (diethyl adipate, CH3CH202C(CH2)4C02CH2CH3)) undergoes cychzation to yield ethyl 2-oxocyclopentanecarboxylate in the presence of ethoxide anion ( OCH2CH3) in ethanol (ethyl alcohol, CH3CH2OH) solvent.

Another example of the acid-catalysed intramolecular cyclization of diazoketones cf. refs. 58, 92, 93) is a high-yielding preparation of polycyclic enones (101) from diazoketones (100). Further reports have appeared on the preparation of fused cyclopentanones by condensations between acetonedicar-boxylate and a-diketones yields are higher if the substituents on the latter substrates are small. An alternative approach to polycyclopentanoids, consisting of successive additions of propargyl alcohol anions to cyclopentanones followed by double dehydrative cyclization and hydrogenation, has been used to prepare the potential dodecahedrane precursor (102) cf ref. 63). The cage compound (103), obtained from 1,4-naphthoquinones and cyclopentadiene, produces the polycyclopentanoid (104) under acyloin condensation conditions. ... 

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 precatalyst 20 led to excellent results in the enantioselective intramolecular crossed benzoin condensation of the aldehyde ketones 24, as shown in Scheme 9.6. The quaternary stereocenter of the acyloins 25 was created with good to very good yields and excellent ee-values. (For experimental details see Chapter 14.20.1). The precatalyst 19 proved to be even more active, and the yields were consistently excellent, albeit accompanied by lower ee-values (63-84%). 

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... 

O. R. 1-9, C. R. Hauser and B. E. Hudson, Jr., The Acctoacetic Ester Condensation and Related Reactions lV-4, S. M. McElvain, The Acyloins 11-4, W. S. Johnson, The Formation of Cyclic Ketones by Intramolecular Acylation VIII-2, D. A. Shirley, The Synthesis of Ketones from Acid Chlorides and Organometallic Compounds of Magnesium, Zinc, and Cadmium. ... 

Scheme 9.160. A Thorpe-Ziegler reaction of 2,6-dicyano-2-methylhexane. First, base treatment allows the dinitrile to undergo acyloin-type condensation (Scheme 9.145) to an imino-nitrile. Hydrolysis of the imine (Scheme 9.65) generates a P-ketonitrUe, which, on further hydrolysis (Scheme 9.46), produces a P-ketocarboxylic acid, which then undergoes decarboxylation (vide infra). Interestingly, the intermolecular version of this reaction is the Thorpe reaction, while the intramolecular version is the Thorpe-Ziegler reaction. See Baron, H. Remfry, F. G. P. Thorpe, J. F. /. Chem. Soc., 1904,85,1726, as well as Ziegler, K. Eberle, H. Ohlinger, H. Liebigs Ann. Chem., 1933,504, 94, and Ziegler, K. Chem. Ber., 1934,67,139.

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