Triflates hydroxy group activation

Evans and coworkers have reported that cationic copper(II)-bis(oxazoline) complexes derived from ferf-leucine are effective Lewis acids for a wide range of enantioselective Diels-Alder reactions. While initial investigations employed cy-clopentadiene as the diene and triflate catalyst 31a (Scheme 24) as the Lewis acid [82], subsequent studies revealed that the reaction rate is strongly dependent on the counterion X [83]. The hexafluoroantimonate catalyst 31b is approximately 20 times more reactive than 31a and is typically more stereoselective. The heightened reactivity and selectivity conferred by catalyst 31b allows access to more substituted adducts in uniformly high enantioselectivity. The active catalyst is easily prepared and robust exposure to air is not deleterious and the reactions may be conducted in the presence of free hydroxy groups. However, reduction of the metal center can be problematic with electron-rich dienes this side reaction may be controlled by a judicious choice of temperature. 

The reaction processes shown in Scheme 8 not only accomplish the construction of an oxepane system but also furnish a valuable keto function. The realization that this function could, in an appropriate setting, be used to achieve the annulation of the second oxepane ring led to the development of a new strategy for the synthesis of cyclic ethers the reductive cyclization of hydroxy ketones (see Schemes 9 and 10).23 The development of this strategy was inspired by the elegant work of Olah 24 the scenario depicted in Scheme 9 captures its key features. It was anticipated that activation of the Lewis-basic keto function in 43 with a Lewis acid, perhaps trimethylsilyl triflate, would induce nucleophilic attack by the proximal hydroxyl group to give an intermediate of the type 44. 

After protection, the a-hydroxy esters can be reduced by DIBAL-H into O-protected a-hydroxyaldehydes that are very useful synthetic intermediates (e.g., leukotrienes,7-9 ionophore antibiotics,10 insect pheremones,11 etc.). The secondary hydroxyl group of the a-hydroxy esters may also be substituted with inversion of configuration after activation as triflates of nosylates (p-nitrobenzenesulfonates) to give a-alkyl esters12 ora-amino esters.13... 

An alternative route to 79b involved nucleophilic displacement from an enantiomerically pure hydroxy acid 82 with a malonate enolate. The OH group was activated as a triflate 83. This method depends on the availability of optically pure hydroxyacid.12 Notice that the wrong enantiomer of 82 must be used as inversion occurs during the SN2 reaction leading to 79b. 

Ottenheijm s group has recently improved procedure VIII.7 (164) (Scheme 33) for the preparation of optically active N-hydroxyamino acid derivatives by a substitution reaction. N-Benzyloxyamino acid esters were obtained from triflates of a-hydroxy esters and O-benzylhy-droxylamine (222). The optical purity of the products was very high. 

In 1995, Pirrung and Bradley " reported the use of dimethoxybenzoin (DMB) carbonate to protect various alcohols, including the 5 -hydroxyl group of nucleosides. The DMB carbonate was synthesized in three steps, starting with methylation of carbonyldiimidazole with methyl triflate followed by addition of 2-(3,5-dimethoxyphenyl)-2-hydroxy-l-phenylethanone to form a relatively stable activated acylating agent. Treatment with an alcohol under basic conditions in nitromethane furnished the protected alcohol 72 in yields that ranged from 42 to 95%. 

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