Iminium salt organocatalysts can provide high selectivity and high efficiency in catalytic asymmetric epoxidation. They are normally used in conjunction with Oxone as the stoichiometric oxidant. Oxone, however, has limited stability and is insoluble in most organic solvents; we report here for the first time the development of a reaction system driven by hydrogen peroxide as the stoichiometric oxidant, involving an unusual double catalytic cycle

Introduction of a pseudoaxial substituent at a stereogenic center adjacent to the nitrogen atom in binaphthyl- and biphenyl-derived azepinium salt organocatalysts affords improved enantioselectivities and yields in the epoxidation of unfunctionalized alkenes. In the biphenyl-derived catalysts, the atropoisomerism at the biphenyl axis is controlled by the interaction of this substituent with the chiral substituent at nitrogen.

No abstract

A range of new biphenylazepinium salt organocatalysts effective for asymmetric epoxidation has been developed incorporating an additional substituted oxazolidine ring, and providing improved enantiocontrol in alkene epoxidation over the parent structure. Starting from enantiomerically pure aminoalcohols, tetracyclic iminium salts were obtained as single diastereoisomers through an atroposelective oxazolidine formation.

RECEIVED MAY 9, 1956 l-Methyl-3-carbethoxy-4-piperidone adds to methyl vinyl ketone t o yield the corresponding 3-( y-ketobutyl) derivative 11, which is readily deearbethoxylated and cyclized t o 1,2,3,4,6,7,8,9-octahydro-2-1nethyl-6-oxoisoqui1ioline (IV). This quinolone is converted by phenyllithiurn or phenylmagnesium bromide t o the 6-phenyl-6-hydroxyoctahydroisoquinoline V, which is readily rearranged by acid to the isomeric 10-hydroxy derivative VI. Both of these carbinols are dehydrated t o the hexahydroisoquinoline VII.This ketone was converted t o the 2-methyl-6-phenyl-6-acetoxyisoquinoline XI, which was found t o bc devoid of analgesic action.Hydrogenation converts I V t o the cis-decahydroisoquinolone VIII.The Michael addition of 1 -methyl-3-carbethoxy-4-piperidone (I) to methyl vinyl ketone proceeds in good yield (76y0) when carried out by the procedure, described in a previous paper of this series,2 for the addition of I to ethyl acrylate. The initial condensation product I1 could be separated and distilled, or be directly decarbethoxylated and cyclized by the method of Wilds and Close3 to the gctahydroisoquinolone IV. A small yield (3y0) of the ketoester 111, resulting from the cyclization of I1 before decarbethoxylation, geiierally accompanied IV.The octahydroisoquinolone IV was reported recently by Marchant and Pinder," who obtained it by two different procedures: (a) a Birch reduction of 1,2,3,4-tetrahydro-~-methoxy-3-methylisoqu~no-line followed by hydrolysis of the resulting hexahydroisoquinoline, and (b) the interaction of 4-diethylaminobutan-2-one with the keto ester I. Earlier, Georgian5 had reported the condensation of methyl vinyl ketone with I to form 2-methyl-6-oxo -9 -carbomethoxy -10 -hydroxydecahydroisoquinoline and the transformation of this product to IV by vigorous treatment with hydrochloric acid, but no details of this work were given.The reaction of phenyllithium with IV, followed by the decomposition of the resulting lithium salt with water, yielded the 6-phenyl-6-hydroxyoctahydroisoquinoline V in 007, yield. When phenylmagnesium bromide instead of phenyllithium was used with IV, and the magnesium salt decomposed with dilute acid, the isomeric I 0-hydroxy compound VI was the product. I t was obtained in only 55-6070 yield; 23-30% of unchanged I V was recovered. The presence of such an amount of the latter compound with the reaction product was doubtless the result of the enolization of the original unsaturated ketone IV by the Grignard reagent; the formation of thc 10-hydroxy derivative VI was due to the action of acid on the initially formed 6-hydroxy derivative V. This acid-catalyzed transformation of V into VI is quite facile and may be accomplished by simply dissolving V in 5% hydrochloric acid. The spectra of the carbinols V and VI were completely devoid of any carbonyl bands