Towards a Truly Efficient, Aerobic, Catalytic Oxidation Protocol

Towards a Truly Efficient, Aerobic, Catalytic Oxidation Protocol A. BuOK A Unique Base 

After screening unsuccessfully a number of different additives, we were gratified to find that 4BuOK uniquely satisfied our requirements. Interestingly, we also noticed that the mode of addition of the various reaction partners played a crucial role in the success of this new procedure (Fig. 8). 

it appeared that addition of the base to the pre-formed CuCl Phen/DBAD complex resulted in rapid deactivation of the system, as demonstrated by the poor conversion of 2-undecanol 21 into the corresponding ketone 22 (Fig. 8, Entry 1) (31). On the other hand, adding BuOK to CuCl-Phen, in the presence of 2-undecanol, followed by the addition of DBAD and heating under a gentle stream of oxygen led to complete conversion of 21 into 22 (Fig. 8, Entry 2). This efficient, catalytic, procedure was then applied to a range of representative alcohols. Some selected examples are shown in Table VI. 

As can be seen from Table VI, secondary aliphatic, allylic, and benzylic alcohols are all quantitatively converted into the corresponding carbonyl derivatives. It is interesting to note that no epimeriza-tion of menthone takes place under these conditions (Entry 3). Furthermore, rather hindered decaline derivatives (Entry 5) are also smoothly oxidized. 

These observations imply that the Cu oxidant is little sensitive to the steric surroundings of the hydroxyl function. The scope of the reaction can be further extended to protected primary p-amino alcohols with equal efficiency. The oxidation of dibenzyl valinol (Entry 6), which contains a tertiary nitrogen atom, proceeds in excellent yield. Moreover, the involvement of a neutral medium is ideally demonstrated by the lack of racemization of both dibenzyl valinal and Boc-prolinal (Entries 6 and 7). Purification of this latter product, which was prepared on a gramm-scale, necessitated only a simple filtration (32). 

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