Heterocoupling Diastereoselective

Cathodic heterocoupling of ketones with allylic alcohols takes place at a carbon fiber cathode with high regio- and diastereoselectivity to afford the corresponding... 

The heterocoupling of carboxylic acids bearing chiral auxiliaries has been used to study the diastereoselectivity of the coupling of Kolbe radicals [204b]. For that purpose, 2-substituted malonic acid amides bound to seven different chiral auxiliaries were coelectrolyzed with different coacids [Eq. (200]- The yields in heterodimer ranged between 13 to 69%, and the diastereoselectivities between 20 and 86% de. 

From a synthetic standpoint the intermolecular pinacolic coupling reaction is limited because only homocoupling reactions are generally practical. Cross-coupling reactions mediated by SmF are restricted to specialized, matched partners [35]. Thus a-dicarbonyl compounds can be heterocoupled with aldehydes, providing facile entry to 2,3-dihydroxy ketones. Although selectivities vary, in some cases the diastereoselectivity of the process can be quite high (Eq. 25). 

The stereochemistry of the products and the regioselectivity of the coupling reaction indicates that adsorption of saturated alkyl radicals is relatively unimportant [20]. Carboxylates which are chiral and non-racemic at the a-position totally lose their optical activity in mixed heterocoupling [21, 22]. This racemization indicates either a free radical as intermediate or its fast desorption-adsorption at the anode. These findings are further supported by the decarboxylation of 3 and 4, which both form the same 1 2 1 mixture of transfrans-, cis,trans- and c ,c -coupled dimer, whilst 5-7 show a slight diastereoselectivity [23, 24]. The latter could be due to some adsorption caused by the phenyl group or double bond and/or by a more effective facial shielding of the radicals (see Chapter 3.3). 

With oxazolidine auxiliaries the diastereomeric heterocoupling products 39 and 40 are obtained in 33% yield (46% de) and 20% yield (45% de) respectively [97], The oxazolidinone 41 as auxiliary leads to a maximum diastereoselectivity of only 9%... 

Camphorsultam, a frequently used chiral auxiliary in diastereoselective syntheses [101], has also been applied in radical reactions [99]. Heterocoupling reactions with 42, 43, and the coacids 33 and 35, afforded the products 44-48 (Eq. 7). The results demonstrate that the diastereoselectivity strongly increases with the steric bulk of the 2-substituent in the malonates 42 and 43, namely 79.5% de with R = tBu and 41.3% de with R = iPr. With increasing bulk of the substituents in the coacid, hydrogen abstraction of the auxiliary substituted radical becomes a major competing reaction leading to 47 and 48. 

For the heterocoupling of 52 and 54 with the coacids 33 and 35, respectively, the temperature dependence (—15 to 53 °C) of the diastereoselectivity has been determined. The yields in heterocoupling products ranged from 9 to 79%, the diastereoselectivity from 2.24 1 to 14.6 1. Side-products were formed by hydrogen abstraction of the ester-substituted radical (3-69%) and with the acid 54, the methylether 60 originating from the cation that is formed by further oxidation of the intermediate benzyl radical (19-33%). 

With both acids 52 and 54 and the coacid 33, the diastereoselectivity is temperature independent. This means that the rate difference for the diastereofacial coupling of the intermediate ester radical is fully entropy controlled. In the corresponding heterocoupling with the radical from the coacid 35, the diastereoselectivity is controlled by activation enthalpy and entropy [102]. 

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