Ylide compounds ketone derivation

Ylides forming from the thermolysis of compound 59 (R1, R2 = Me, R3 = Ar, R4 = OMe) reacted also with dimethyl acetylenedicarboxylate (DMAD) or diethyl azodicarboxylate (DEAD) <2003TL5029> in the presence of aldehydes, quinones <2001TL2043>, or ketones <20020L2821, 20000L3501> to give 2,5-dihydrofuran derivatives, for example, 67 (Rs = Me, Et). 

Decarboxylation of 1,3-dimethylorotic acid in the presence of benzyl bromide yields 6-benzyl-1,3-dimethyluracil and presumably involves a C(6) centered nucleophilic intermediate which could nonetheless have either a carbene or ylide structure. Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry has been used to explore the gas-phase reactions of methyl nitrate with anions from active methylene compounds anions of aliphatic ketones and nitriles react by the 5n2 mechanism and Fco reactions yielding N02 ions are also observed nitronate ions are formed on reaction with the carbanions derived from toluenes and methylpyridines. 

These compounds come from methylenation reactions of the corresponding carbonyl derivative by means of an ylide. Several experimental conditions have been described. In most cases, CF2Br2 and HMPT (hexamethyl phosphorotriamide) are employed. The reaction occurs with aldehydes as well as with ketones in the furanose and pyranose series. The reaction can also be performed with lactones the fluoromethyl group is then introduced in the anomeric position. With these substrates, the Julia olefmation, which uses difluoromethyl sulfone, has also been reported to be an efficient method. Some examples of these reactions are shown in Figure 6.24. 

One problem in the anti-selective Michael additions of A-metalated azomethine ylides is ready epimerization after the stereoselective carbon-carbon bond formation. The use of the camphor imines of ot-amino esters should work effectively because camphor is a readily available bulky chiral ketone. With the camphor auxiliary, high asymmetric induction as well as complete inhibition of the undesired epimerization is expected. The lithium enolates derived from the camphor imines of ot-amino esters have been used by McIntosh s group for asymmetric alkylations (106-109). Their Michael additions to some a, p-unsaturated carbonyl compounds have now been examined, but no diastereoselectivity has been observed (108). It is also known that the A-pinanylidene-substituted a-amino esters function as excellent Michael donors in asymmetric Michael additions (110). Lithiation of the camphor... 

Fluoroolefins may be prepared by the reaction of Wittig reagents and other pho sphorus-contaimng ylides with fluorinated carbonyl compounds. (A discussion of the fluorinated Wittig reagents or other fluorinated phosphorus reagents with nonfluonnated carbonyl compounds is on page 581.) Tnphenylphosphoranes, derived from alkyltriphenyl phosphonium salts, react with 1,1,1-trifluoroacetone [3/] or other trifluoromethyl ketones [32, 33] (equation 26) (Table 10). 

Oxidative methanolysis of azetidinone 176 followed by hydrogenolysis of compound 177 afforded /3-lactam 178, which was protected to obtain the protected amine 179. The best conditions for rearrangement of 179 were found using TFA. Conversion of compound 180 to carbacephem 183 was accomplished by ketone reduction, alcohol protection, and elimination of methanol. Synthesis of carbacephem derivative 186 has been performed by rhodium(n)-catalyzed cycliza-tion of iodonium ylide 185 <1997TL6981> (Scheme 33). The iodonium ylide 185 was easily prepared from the corresponding /3-keto ester 184 and [(diacetoxy)iodo]benzene in good yield. 

While most of the initial studies have involved the transition metal-catalyzed decomposition of a-carbonyl diazo compounds and have been reviewed [3-51], it appears appropriate to highlight again some milestones of these transformations, since polycyclic structures could be nicely assembled from acyclic precursors in a single step. Two main reactivities of metalo carbenoids derived from a-carbonyl diazo precursors, namely addition to a C - C insaturation (olefin or alkyne) and formation of a ylid (carbonyl or onium), have been the source of fruitful cascades. Both of these are illustrated in Scheme 27 [52]. The two diazo ketone functions present in the same substrate 57 and under the action of the same catalyst react in two distinct ways. The initially formed carbenoid adds to a pending olefin to form a bi-cyclop. 1.0] intermediate 58 that subsequently cyclizes to produce a carbonyl ylide 59, that is further trapped intramolecularly in a [3 + 2] cycloaddition. The overall process gives birth to a highly complex pentacyclic structure 60. 

Ketones.- A new synthesis of cyclopentadienes by the reactions of allylidenetriphenylphosphonium ylides (40) with a-halogenocarbonyl compounds has been reported.33 Wittig reactions of the ylide derived from the phosphonium salt (41) provide the hydrazones (42).34 This reaction combined with hydrolysis of (42) constitutes a method for the n-i-2 homologation of ketones and aldehydes (Scheme 8). 

An epoxidation reaction utilizing a complex diazo compound is shown in equation (30)." The addition of diazomethane to highly electron-deficient esters has been reported to yield 2-alkoxy-2-substituted epoxides (equation 31)." The stereoselectivity of the addition of diazomethane to pentulose derivative (20) was shown to be superior to that obtained using sulfur ylides, giving ratios of 95 5 in favor of (21 equation 8). However, the yields were unstated, and the products were accompanied in most cases by significant amounts of homologous ketone. ... 

One more carbene-based route to oxapenam derivatives utilizes the Cu-catalyzed decomposition of diazo compounds 547 via cyclic sulfonium ylide 548. The protocol is effective for 5-aryl (80H1999) and 5-heteryl-substituted (82H1597) diazo compounds of type 547. Oida and co-workers succeeded in obtaining oxapenam 549 (33%) by Cu(acac)2-catalyzed transformation of 5-alkenyl-substituted diazo ketones 550. The attempted synthesis of... 

The metal-catalyzed decomposition of diazo compounds 603 provides access to a variety of cephem derivatives (Scheme 30). Copper-mediated cyclization of diazo ketone 603 (R = Et) gives 3-oxocepham through sulfo-nium ylide formation followed by j8-elimination (80H1999). The formation of cephem derivatives 604 and 605 presumably involves the intermediacy of ylide 606 (R = Ac, ArCH2) and its subsequent rearrangement. A more sophisticated mechanism is proposed for the formation of 607 and 608 (83H205). 

The transformation of penicillin-derived diazo ketones 696 into compounds 697a and b with the nitrogen atom in the ring fusion position on treatment by Cu(acac)2 proceeds via a sulfonium ylide with subsequent rearrangement (77T547 80TL2451 82H1647). 

Allyldiethylamine behaves similarly, but the yields are low since neither the starting amine nor the products are stable to the reaction conditions. For the efficiency of the cyclopropanation of the allylic systems under discussion, a comparison can be made between the triplet-sensitized photochemical reaction and the process carried out in the presence of copper or rhodium catalysts whereas with allyl halides and allyl ethers, the transition metal catalyzed reaction often produces higher yields (especially if tetraacetatodirhodium is used), the photochemical variant is the method of choice for allyl sulfides. The catalysts react with allyl sulfides (and with allyl selenides and allylamines, for that matter) exclusively via the ylide pathway (see Section 1.2.1.2.4.2.6.3.3. and Houben-Weyl, Vol. E19b, pll30). It should also be noted that the purely thermal decomposition of dimethyl diazomalonate in allyl sulfides produces no cyclopropane, but only the ylide-derived product in high yield.Very few cyclopropanes have been synthesized by photolysis of other diazocarbonyl compounds than a-diazo esters and a-diazo ketones, although this should not be impossible in several cases (e.g. a-diazo aldehydes, a-diazocarboxamides). Irradiation of a-diazo-a-(4-nitrophenyl)acetic acid in a mixture of 2-methylbut-2-ene and methanol gave mainly l-(4-nitrophenyl)-2,2,3-trimethylcyclo-propane-1-carboxylic acid (19, 71%) in addition to some O-H insertion product (10%). ... 

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