Retro fragmentation

These enoximes can be prepared through available annelated six-membered cyclic nitronates (391) by their silylation giving rise to the iminium cations A, whose deprotonation affords annelated 2H-5,6-dihydrooxazines (392). After the known retro-fragmentation (490), the latter compounds are transformed into the target conjugated en oximes (395). 

Another approach, attributable to Warrener, induces the retro reaction under much milder conditions by ensuring that the dienophile retro fragment is a stabilized (aromatic) spedes.Again, this route has been applied to the parent compound (Section II,A Eq. 5), but it has also been employed in the synthesis of 2-ethoxycarbonylisoindole and of 4,5,6,7-tetrafluoro-2-methylisoindole.17... 

The mass spectrum of 2-pyrone shows an abundant molecular ion and a very prominent ion due to loss of CO and formation of the furan radical cation. Loss of CO from 4-pyrone, on the other hand, is almost negligible, and the retro-Diels-Alder fragmentation pathway dominates. In alkyl-substituted 2-pyrones loss of CO is followed by loss of a hydrogen atom from the alkyl substituent and ring expansion of the resultant cation to the very stable pyrylium cation. Similar trends are observed with the benzo analogues of the pyrones, although in some cases both modes of fragmentation are observed. Thus, coumarins. 

Also the mirror image of the strueture I, eorreetly denoted as exo-3,10-dihydroxy-3,5,8,10-tetra-methyltrieyelo[6.2.2.0 ]dodeea-5,l 1-diene-4,9-dione, would be possible sinee enantiomers are not differentiated by NMR. A retro-Diels-Alder fragmentation of I to CsH/oO explains why the moleeular ion eorresponding to the moleeular formula C16//20O4 is not deteeted in the mass spee-trum. The metabolite I eould be formed by Diels-Alder dimerisation of 1,5-dimethyleyelohexa-l,3-dien-5-ol-6-one J as the primary metabolite which acts as diene and dienophile as well... 

Molecular orbital calculations indicate that cyclo C-18 carbyne should be relatively stable and experimental evidence for cyclocarbynes has been found [25], Fig. 3B. Diederich et al [25] synthesised a precursor of cyclo C-18 and showed by laser flash heating and time-of flight mass spectrometry that a series of retro Diels-Alder reactions occurred leading to cyclo C-18 as the predominant fragmentation pattern. Diederich has also presented a fascinating review of possible cyclic all-carbon molecules and other carbon-rich nanometre-sized carbon networks that may be susceptible to synthesis using organic chemical techniques [26]. 

Carboximide 160, the C35-C42 fragment, can be traced retro-synthetically to phosphonate 169 and aldehyde 170. In the synthetic direction, the C35-C36 bond in 160 could be constructed by an intermolecular Horner-Wadsworth-Emmons (HWE)70 coupling of intermediates 169 and 170. Reduction of the unsaturated coupling product and exchange of silyl protecting groups would then furnish compound 160. 

Several chemical transformations in the chlorin series were discovered during the course of Woodward s total synthesis of chlorophyll a.3a d An important reaction in the final steps of this total synthesis is the removal of an a-oxo acid ester residue from the 17-position of the chlorin 22, which proceeds very smoothly in the presence of base by a retro-aidol-type fragmentation to yield the chlorin isopurpurin methyl ester (23) which is also available by degradation of chlorophyll a, so that at this point of the synthesis synthetically derived material could be compared with an authentic sample prepared from natural chlorophyll a. 

This retro-aldol-typc fragmentation is possible because the chlorin chromophore stabilizes the anion formed on loss of the a-oxo acid residue. A related reactivity is observed in the reduction of 3-vinylchlorins, e.g. 24, to 3-ethylporphyrins, e.g. 25, in the presence of hydrogen iodide in acetic acid. The mechanism of this reaction can be represented as a sequence of tautomeric reactions which lead to the completely conjugated porphyrin system.32c-40-54... 

It should be noted that the cyano group is lost by a retro-Claisen-type fragmentation 6->7 which gives automatically the pyrrocorphin 7 on the hexahydro oxidation level rather than by a /i-elimination-type process which would give a tetrahydroporphyrin. A similar fragmentation process has been observed in the total syntheses of chlorophyll a (sec Section 1.2.1.) and of a tolyporphin model (see Section 1.3). 

Scheme 8.52 Retro-aldol fragmentation of an epoxide-derived hemiacetal.

Another example of a [4S+1C] cycloaddition process is found in the reaction of alkenylcarbene complexes and lithium enolates derived from alkynyl methyl ketones. In Sect. 2.6.4.9 it was described how, in general, lithium enolates react with alkenylcarbene complexes to produce [3C+2S] cycloadducts. However, when the reaction is performed using lithium enolates derived from alkynyl methyl ketones and the temperature is raised to 65 °C, a new formal [4s+lcj cy-clopentenone derivative is formed [79] (Scheme 38). The mechanism proposed for this transformation supposes the formation of the [3C+2S] cycloadducts as depicted in Scheme 32 (see Sect. 2.6.4.9). This intermediate evolves through a retro-aldol-type reaction followed by an intramolecular Michael addition of the allyllithium to the ynone moiety to give the final cyclopentenone derivatives after hydrolysis. The role of the pentacarbonyltungsten fragment seems to be crucial for the outcome of this reaction, as experiments carried out with isolated intermediates in the absence of tungsten complexes do not afford the [4S+1C] cycloadducts (Scheme 38). 

The retro Diels-Alder reaction usually requires high temperatures in order to surmount the high activation barrier of the cycloreversion. Moreover, the strategy of retro Diels-Alder reaction is used in organic synthesis to mask a diene fragment or to protect a double bond [47]. Some examples are illustrated in Scheme 1.11. 

Mandelbaum A. Stereochemical Effects in the Retro-Diels-Alder Fragmentation... 

Keywords retro-Diels-Alder fragmentation occurring in gas-phase, fragmentation in mass spectrometry... 

A few routes to new silenes, usually involving flash vacuum pyrolysis at high temperatures, have been reported. Silenes were proposed as the result of the thermal expulsion of trimethylmethoxysilane, or a similar volatile fragment, from the starting material but frequently, proof that the silenes proposed to account for the observed products were in fact formed was not provided.116 119 The other thermal route employed was the retro-Diels-Alder regeneration of a silene from an adduct with an aromatic compound—often a 9,10-anthracene or 1,4-naphthalene adduct or, in some cases, a 1,4-benzene adduct, as illustrated in Eq. (19).120... 

Fragmentation Group-transfers, retro-ene, cyclo-reversions. 

Mass spectra of the cis- and /ram-isomers of the pyrimido[2,TA [l,3]thiazin-6-ones 294 and 295 were studied. Retro-Diels-Alder fragmentation of the hydrocarbon ring was of medium to low stereospecificity. A number of highly selective processes were discovered allowing differentiation between stereoisomers <1996RCM721>. The mass spectral fragmentation pattern of 296 was studied in detail <1996PS(113)67>. 

The mass spectra of compounds 10 and 11 were consistent with their assigned structures and showed molecular mass at mlz 432 due to the dimeric form, while the presence of the base peak at m/z 217 accounts for an easy retro-dimerization <1989JOC3062>. The fragmentation pattern of compound 4 has already been discussed in CHEC-II(1996) <1996CHEC-II(8)707>. 

Unfortunately, upon treating hydroxy ketone 56 with MeLi for extended reaction times, some sort of fragmentation reaction appeared to occur (Scheme 8.15). While the desired addition product 63 was not seen, the fragmentation that took place may be attributed to a retro-aldol reaction through intermediates such as 60 and 61. The tentatively assigned structure of final product 62 is shown, although it was not fully... 

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