The Dehydrogenation of Steroidal Δ^3,5-Enol Ethers with Dichlorodicyanoquinone (DDQ)¹

Abstract

The reaction of dichlorodicyanoquinone (DDQ) with 3-ethoxy A3'%eroids ( I ) leads, in the absence of water, to l14,6-trien-3-ones (VI). The sequence is pictured as proceeding via hydride abstraction a t C-7, lose of a C-2 proton from the oxonium intermediate (11), followed by hydride loss from C-1. I n the presence of water, hydrolysis of the oxonium species (11) is faster than (2-2 proton loss leading to a high yield of 4,6-dien-3-oneThe quinone-mediated dehydrogenation of steroidal A4-3-ketones has proven to be a reaction of considerable practical application and of intrinsic theoretical interest. Agnello and Laubach2 found that a t elevated temperatures chloranil converted A4-3-keto steroids into the corresponding 6-dehydro steroids and proposed that the reaction proceeded via the A36-enol followed by C-7 hydride ion abstraction. Cited in support of the enol mechanism were the observations that a A5-3-ketone and a A36-enol ether underwent conversion by chloranil to the A46-dienone a t a much greater rate than was the A4-3-ketone. In contrast to the behavior of chloranil, the closely related but higher potential quinone, 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), was found by Burn, Kirk, and PetrowS to introduce 1,2 rather than 6 7-unsaturation into A4-3-ketone substrates. Ringold and Turner4 rationalized the different behavior of the two quinones as oxidation of the kinetically determined enol in the case of DDQ and of the thermodynamically more stable enol in the case of chloranil and demonstrated that in the presence of anhydrous hydrogen chloride, DDQ led to 6,7 dehydrogenation. This latter observation was construed to be evidence for an enol-dependent reaction since in the presence of strong acid the Aa5-enol should be the kinetically favored as well as the more stable enol. It was thus of interest to investigate the interaction of DDQ with fixed derivatives of this enol, and, for this purpose the oxidation of a number of 3-etho~yandrost-3~5

Protonation of conjugated carbonyl groups in sulfuric acid solutions. III. α,β-Unsaturated ketosteroids

“…They are commercial materials, except for conlpounds 18 and 19, which were synthesized from 1 and testosterone propionate, respectively, by dehydrogenation with chloranil in t-butyl alcohol (3). Compounds 18 and 19 melted a t 168.5-169" and 135-136", respectively, and their ultraviolet spectra in ethanol agreed with literature data (4,5 The method and apparatus used to determine pKDII+ have been described previously (1). However, in the present work an additional complication is present.…”

Specificity in enzyme inhibition. 2. .alpha.-Aminohydroxamic acids as inhibitors of histidine decarboxylase and 3,4-dihydroxyphenylalanine decarboxylase

“…Histidine hydroxamic acid 4 showed more specificity for inhibition of the histidine decarboxylase than for the inhibition of dopa decarboxylase while the tryptophan analog 5 had little activity in the inhibition of the dopa decarboxylase but was as active as the histidine analog in the inhibition of histidine decarboxylase. The above compounds can be compared (Table I) with a-methyldihydroxyphenylalanine (6) as a specific inhibitor of dopa decarboxylase and with 4-(4imidazolyl)-3-amino-2-butanone (7) as a specific inhibitor of histidine decarboxylase.…”

DDQ as a versatile and easily recyclable oxidant: a systematic review

“…However, in the presence of water, the reaction proceeds quickly through hydrolysis of the intermediate 84 rather than proceeding through a second path whereby it loses a proton to generate 86 in good yield (Scheme 37). 62 In 1994, Böhme and Kempe proposed a mechanism for the formation of steroids-based uorescent probes with an aliphatic side chain or without it. Starting from steroidal alcohols 87 and 91, they prepared different intermediate compounds via DDQ-assisted oxidation (Scheme 38).…”

“…However, in the presence of water, the reaction proceeds quickly through hydrolysis of the intermediate 84 rather than proceeding through a second path whereby it loses a proton to generate 86 in good yield ( Scheme 37 ). 62 …”