An Efficient Regioselective and Diastereoselective Synthesis of the Epoxy-quinol Functionality as Building Block for the Manumycin Antibiotics by the Sequence of Photooxygenation, Reduction and Weitz-Scheffer Epoxidation

Abstract

The photooxygenation of the acetanilide 2 affords the hydroperoxide 3, which by titanium-tetraisopropoxide-catalyzed reduction with dimethyl sulfide gives the corresponding quinol 4. Regioselective and diastereoselective Weitz-Scheffer epoxidation of the latter by tert-butyl hydroperoxide (TBHP) and DBU as base catalyst leads to the cis-epoxy quinol 1, the essential functionality in Manumycin antibiotics.

Syntheses of Natural Products Having an Epoxyquinone Structure

“…69 Aminophenol 62 was photooxygenated in the presence of TPP as a photosensitizer to give hydroperoxide 63, reduction of which with dimethyl sulfide in the presence of titanium tetraisopropoxide afforded alcohol 64. Weitz-Scheffer epoxidation of 64 was reported to take place in a completely diastereoselective manner due to participation of the hydroxyl group to give LL-C10037R analogue 65.…”

“…Weitz−Scheffer epoxidation of 64 was reported to take place in a completely diastereoselective manner due to participation of the hydroxyl group to give LL-C10037α analogue 65 .

10 Kilic's Synthesis of LL-C10037α Analogue 65 (Reprinted with Permission from Ref . Copyright 2002 Thieme)

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“…Kilic's Synthesis of LL-C10037α Analogue 65 (Reprinted with Permission from Ref . Copyright 2002 Thieme) …”

“…Although, for the purpose of construction of the quinone structure, oxidation of hydroquinone with hypervalent iodine reagents has been widely employed, Kilic and co-workers reported an alternative method employing photooxygenation, in 2002 (Scheme 10). 69 Aminophenol 62 was photooxygenated in the presence of TPP as a photosensitizer to give hydroperoxide 63, reduction of which with dimethyl sulfide in the presence of titanium tetraisopropoxide afforded alcohol 64. Weitz-Scheffer epoxidation of 64 was reported to take place in a completely diastereoselective manner due to participation of the hydroxyl group to give LL-C10037R analogue 65.…”

Efficient Synthesis of p-Quinols Using Catalytic Hypervalent Iodine Oxidation of 4-Arylphenols with 4-Iodophenoxyacetic Acid and Oxone

“…8,9) A commonly used methods for preparation of p-quinols is 4-substituted phenol oxidation. Among many reported oxidants for the oxidation of phenols, [10][11][12][13][14][15][16][17] hypervalent iodine(III) oxidants such as phenyliodine(III) diacetate (PIDA) and phenyliodine(III) trifluoroacetate (PIFA) are typically used [18][19][20][21] because of the non-toxic nature of hypervalent iodine(III) reagents and the method's simplicity. [22][23][24][25][26] However, this approach often gives low yields of the desired product because of competitive oligomerization, especially in the case of oxidation of 4-arylphenols.…”