With DDQ

Donor substituents on the vinyl group further enhance reactivity towards electrophilic dienophiles. Equations 8.6 and 8.7 illustrate the use of such functionalized vinylpyrroles in indole synthesis[2,3]. In both of these examples, the use of acetyleneic dienophiles leads to fully aromatic products. Evidently this must occur as the result of oxidation by atmospheric oxygen. With vinylpyrrole 8.6A, adducts were also isolated from dienophiles such as methyl acrylate, dimethyl maleate, dimethyl fumarate, acrolein, acrylonitrile, maleic anhydride, W-methylmaleimide and naphthoquinone. These tetrahydroindole adducts could be aromatized with DDQ, although the overall yields were modest[3]. 

Dioxopiperazines are amongst the most ubiquitous of natural products (75FOR(32)57) and they are formally derived by the cyclodimerization of a-amino acids (69CCC4000) or their esters. A number of methods are available for their oxidation to the corresponding pyrazines. Treatment of 2,5-dioxopiperazines with triethyl- or trimethyl-oxonium fluorobor-ate followed by oxidation with DDQ, chloranil or iodine results in pyrazine formation, usually in high yields (Scheme 63) (72JCS(P1)2494). 

Cleavage of MPM, DMPM, and TMPM ethers with DDQ in CHzCIs/HzO at 20 ... 

Ph3C BF, CH2CI2 or CH3CN, H2O. In this case the reaction with DDQ failed to go to completion. This was attributed to the reduced electron density on the aromatic ring because of its attachment at the more electron-poor anomeric center. 

This example shows that overoxidation of allylic alcohols may occur with DDQ. ... 

This ether has properties similar to the p-methoxybenzyl (MPM) ether except that it can be repioved from an alcohol with DDQ in the presence of an MPM group with 98% selectivity The selectivity is attributed to the lower oxidation potential of the DMPM group 1.45 V for the DMPM versus 1.78 V for the MPM. 

These groups are readily cleaved with Ph3C BF, 0°, 6 min, 90% yield 0°, 15 min, 90% yield. It should also be possible to cleave these carbonates with DDQ like the corresponding methoxy- and dimethoxy phenyl methyl ethers. 

The acetal can also be cleaved with DDQ (CH2C12, H2O, 66% yield) to afford the monobenzoate. Treatment of a 3,4-dimethoxybenzyl ether containing a free hydroxyl with DDQ (benzene, 3 A molecular sieves, rt) affords the 3,4-dimethoxy-benzylidene acetal. ... 

An explanation for the difference in behavior of chloranil and DDQ towards A -3-ketones was first provided by Ringold and Turner. The A -enol (67) is produced faster than the more stable A -enol (68) but is not attacked appreciably by chloranil, which lacks sufficient oxidizing potential. Instead, the more easily oxidized A -enol (68) is dehydrogenated to (69) as it is produced. With DDQ, the faster formed A -enol (67) can be effectively dehydrogenated and the A -3-ketone (70) is formed ... 

The reaction of androst-4-ene-3,17-dione with DDQ in refluxing benzene or dioxane leads to the A -3-ketone as the major product, although small amounts of A -3-ketone and A -3-ketone are also produced. The latter arises from the A -3-ketone, since the A -3-ketone is not dehydrogenated further under the usual reaction conditions. A -3-Ketone production is more favored in benzene than it is in dioxane substituents at C-6 can also influence this selectivity. A recent thorough investigation of the mechanism of dehydrogenation of 3-ketones under neutral and acidic condi-... 

A convenient synthesis of A -3-ketones in the 5 5 series uses DDQ in one step. This introduction has to be done indirectly because of the unfavorable direction of enolization. In this scheme, advantage is taken of the equilibrated formylation at C-2 of 5i5-3-ketones. Dehydrogenation of the 2-formyl derivative (72) proceeds rapidly with DDQ and deformylation is achieved in the presence of a homogeneous catalyst. A related approach involves preparation of the 2i -bromo-5i5-3-ketone by bromination of the 2-formyl compound (72). ... 

A cleavage reaction reminiscent of that already noted with chloranil " has been observed at room temperature with DDQ. This reaction is remarkable in that it stops at the dihydrophenanthrene stage (78, 79) and takes place... 

Androst-4-ene-3,17-dione (83) is converted into the enol ether (84) by reaction with triethyl orthoformate. Treatment of the enol ether (84) with DDQ in aqueous acetone gives the title dienone (85). This method is particularly suitable for A" -3-ketones substituted at the 6-position. 

Testosterone acetate (86) is treated with DDQ in refluxing benzene. It is necessary to purify the product by a rough chromatography and by crystallization.This reaction is normally accompanied by some A -introduc-tion, even in dry benzene, which gives the most selective reaction. Pure -3-ketones are normally obtained in 55-75% yields by this route (see, for example, ref. 171). 

Ketones may be prepared from 5a- and 5/5-saturated-3-ketones, A -3-ketones, A -3-ketones and 5a-A -3-ketones. At one time it was the only direct chemical alternative to microbiological methods for the preparation of the prednisone type of corticoids. A -Double bond formation is not observed, although A -trienones can be prepared from A -3-ketones. In common with DDQ, selenium dioxide is not normally useful for the preparation of A -3-ketones from 5a-3-ketones or A -3-ketones from 5j5-3-ketones. 

Cleavage of MPM, DMPM, andTMPM Ethers with DDQ in CH2CI2/H2O at 20°... 

Note that this method does not work on simple esters. In addition, TMSOCH2CH2OTMS/TMSOTF has been used to effect this conversion.The same process was used to introduce the cyclohexyl version of this ortho ester in a quassinoid synthesis. Its cleavage was effected with DDQ in aqueous acetone.(R,R)-2,3-Butanediol can be used to resolve the lactone. 

The MPM group was used in the preparation of a variety of triazoles, imidazoles, and pyrazoles. It is readily cleaved with CF3COOH at 65° (52-100% yield). It is also cleaved from a pyrido[2,3-Z ]indole with DDQ, 88% yield. ... 

DDQ, CHCI3, H207 The 3,4-dimethoxybenzyl group could be cleaved from a sulfonamide with DDQ (8-50% yield). ... 

Pyrazo[l,5-a]quinolines were synthesized by reaction of acrylates with 1-(Af-methylamino)quinolines 430 to afford the corresponding Michael addition product 431 which upon dehydrogenation with DDQ gave 432. 

Treatment of 8-azidomethylperhydropyrido[l,2-c]pyrimidin-l-one 157 with methyl triflate and catalytic hydrogenation of the azide group led to the formation of tricyclic guanidine derivative 158 (01JA8851). Hydroxy group of 149 was protected with methoxymethyl chloride, and the p-methoxybenzyl protecting group (PMB) was eliminated by treatment with DDQ. 

Halogenation of the 7 position also proves compatible with good antiinflammatory activity. Construction of this compound, aclomethasone dipropionate (80), starts by introduction of the required unsaturation at the 6,7 position by dehydrogenation with DDQ (76). The highly hindered nature of the hydroxyl at position 17 requires that a roundabout scheme be used for formation of the corresponding ester. Thus treatment of 76 with ethyl orthoformate affords first the cyclic orthoformate This then rearranges to the 17 ester on exposure to acetic acid. Acylation of the 21 alcohol is accomplished in straightforward fashion with... 

The completion of the synthesis of the polyol glycoside subunit 7 requires construction of the fully substituted stereocenter at C-10 and a stereocontrolled dihydroxylation of the C3-C4 geminally-disub-stituted olefin (see Scheme 10). The action of methyllithium on Af-methoxy-Af-methylamide 50) furnishes a methyl ketone which is subsequently converted into intermediate 10 through oxidative removal of the /j-methoxybenzyl protecting group with DDQ. Intermediate 10 is produced in an overall yield of 83 % from 50) , and is a suitable substrate for an a-chelation-controlled carbonyl addition reaction.18 When intermediate 10 is exposed to three equivalents of... 

The next key step, the second dihydroxylation, was deferred until the lactone 82 had been formed from compound 80 (Scheme 20). This tactic would alleviate some of the steric hindrance around the C3-C4 double bond, and would create a cyclic molecule which was predicted to have a greater diastereofacial bias. The lactone can be made by first protecting the diol 80 as the acetonide 81 (88 % yield), followed by oxidative cleavage of the two PMB groups with DDQ (86% yield).43 Dihydroxylation of 82 with the standard Upjohn conditions17 furnishes, not unexpectedly, a quantitative yield of the triol 84 as a single diastereoisomer. The triol 84 is presumably fashioned from the initially formed triol 83 by a spontaneous translactonization (see Scheme 20), an event which proved to be a substantial piece of luck, as it simultaneously freed the C-8 hydroxyl from the lactone and protected the C-3 hydroxyl in the alcohol oxidation state. 

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