An Efficient Transformation of Cyclic Ene-carbamates into .OMEGA.-(N-Formylamino)carboxylic Acids by Ruthenium Tetroxide Oxidation

Abstract

The high-valent metal-promoted oxidation of a carboncarbon double (CϭC) bond with cleavage is a promising synthetic route to the corresponding carbonyl compounds. This chemistry has been extensively studied.1) Ruthenium tetroxide (RuO 4 ) is well known as a highly effective oxidant, [2][3][4] and the oxidative cleavage of simple CϭC bonds is one of the most common reactions between RuO 42) and alkenes. However, only a low effort regarding the oxidative cleavage of the CϭC double bond to the corresponding carbonyl compounds in enol ethers, enol esters and enamines has been made to date. To the best of our knowledge, there are only two papers. The first example of this type of reaction was described by Desai and co-workers, 5) who reported one case that attempted the cleavage of a CϭC bond in steroidal enamines. Torii and co-workers 6) revealed the procedure for the RuO 4 oxidative cleavage of enolic olefins including two six-membered nitrogen-containing heterocyles that afforded the carbonyl compounds under the conditions using the substrate in a suspension of CCl 4 and H 2 O in the presence of RuO 2 · xH 2 O and NaIO 4 .On the other hand, we have been working on the transformation of cyclic [7][8][9] and acyclic [10][11][12] N-acyl amines into the corresponding lactams and imides including the natural products [13][14][15][16][17] by the RuO 4 oxidation. The double layer oxidation method using a catalytic amount of RuO 2 hydrate, an excess of a NaIO 4 aqueous solution and ethyl acetate system was established for these purposes in our laboratory. In addition, it was recently reported that the single layer RuO 4 oxidation 18) of cyclic N-acyl amines using a tert-butanol and NaIO 4 aqueous solution system gave the ring opened wamino acids (Chart 1). We now report that the simple RuO 4 oxidation of various cyclic ene-carbamates including the optically active one into the corresponding w-(N-formylamino)carboxylic acids and the formal synthesis of L-carnitine as the utilization of this RuO 4 oxidation. Results and DiscussionThe substrates, five-, six-and seven-membered cyclic enecarbamates (1a, 2a, 3a), were prepared from the corresponding N-acyl amines via the N-acyl lactams in good yields by the reported method. 19) We have previously tested the utility of the urethane type N-protecting groups, 9) benzyloxycarbonyl (Z), p-nitrobenzyloxycarbonyl (PNZ), trichloroethoxycarbonyl (Troc) and tert-butoxycarbonyl (Boc) groups for the RuO 4 oxidation of the cyclic amines, and found the following three points: (1) the Z group is decomposed by RuO 4 that produced a low yield of products, (2) the PNZ and Troc groups generally require a longer reaction until the starting materials disappear, and (3) the Boc group is stable, accelerates the oxidation, and affords the products in high yields. In addition, the Boc group can be easily removed from the Nprotected amines by common procedures. Thus, we selected the Boc group as the N-protecting group for this RuO 4 oxidation.RuO 4 Oxidation of Ene-carbamates The oxidation of N-tert-but...

Manganese-Catalyzed Desaturation of N-Acyl Amines and Ethers

“…Because of the fact that α,β-unsaturated cyclic ene-carbamates are versatile intermediates for the synthesis of various nitrogen-containing bioactive molecules, ,− it would be highly advantageous if the viability of the desaturation reaction was demonstrated on a larger scale. Accordingly, we then carried out a gram-scale reaction on 1a to explore reaction scalability.…”

A Unified Approach to Polycyclic Alkaloids of the Ingenamine Estate: Total Syntheses of Keramaphidin B, Ingenamine, and Nominal Njaoamine I

“…For proof-of-concept, compound 17 carrying a butenyl substituent was prepared by O-silylation of commercial 14 followed by regioselective C–H oxidation with RuO 2 cat./NaIO 4 (Scheme ). , The elaboration of 15 thus formed into 16 was also high yielding. A particularly noteworthy improvement concerns the use of a modified Saegusa-type decarboxylative dehydrogenation catalyzed by Pd 2 (dba) 3 to set the internal double bond of the Michael acceptor 17 ; the formation of the original building block 5 , which is much more electrophilic and hence more sensitive, had mandated stoichiometric selenation/selenoxide elimination for this purpose …”

Total Synthesis of Putative Xestocyclamine A

“…O-Silylation of cheap 4 and subsequent regioselective C-H activation with RuO2 cat./NaIO4 furnished lactam 5 in 55% yield over both steps on a >18 g scale. 20 Deprotonation with excess LiHMDS was followed by sequential addition of allyl chloroformate and PhSeCl; the resulting product was treated with H2O2 under strictly neutral conditions to give product 6 in high yield, again on a multigram scale. Because of its excellent acceptor properties, 6 must be stored at low temperature under inert conditions.…”