Retro-Diels Alder

C, b.p. 170 C (decomp.), has a characteristic odour. It is the Diels-Alder product of cyclopentadiene reacting with itself, the exo-form being formed most rapidly but the endo-form is thermodynamically favoured. At temperatures above ISO C a retro-Diels-Alder reaction occurs and cyclopentadiene monomer is regenerated see diene reactions. 

In summary, it seems that for most Diels-Alder reactions secondary orbital interactions afford a satisfactory rationalisation of the endo-exo selectivity. However, since the endo-exo ratio is determined by small differences in transition state energies, the influence of other interactions, most often steric in origin and different for each particular reaction, is likely to be felt. The compact character of the Diels-Alder activated complex (the activation volume of the retro Diels-Alder reaction is negative) will attenuate these eflfects. The ideas of Sustmann" and Mattay ° provide an attractive alternative explanation, but, at the moment, lack the proper experimental foundation. 

Analogously, the effect of micelles on the rate of the unimolecular retro Diels-Alder reaction has been studied. Also here only a modest retardation" or acceleration" is observed. Likewise, the presence of micelles has been reported to have a modest influence on an intramolecular Diels-Alder reaction . Studies on the endo-exo selectivity of a number of different Diels-Alder reactions in micellar media lead to comparable conclusions. Endo-exo selectivities tend to be somewhat smaller in micellar solutions than in pure water, but still are appreciably larger than those in organic media In contrast, in microemulsions the endo-exo selectivity is reduced significantly" ... 

The observation that in the activated complex the reaction centre has lost its hydrophobic character, can have important consequences. The retro Diels-Alder reaction, for instance, will also benefit from the breakdown of the hydrophobic hydration shell during the activation process. The initial state of this reaction has a nonpolar character. Due to the principle of microscopic reversibility, the activated complex of the retro Diels-Alder reaction is identical to that of the bimoleciilar Diels-Alder reaction which means this complex has a negligible nonpolar character near the reaction centre. O nsequently, also in the activation process of the retro Diels-Alder reaction a significant breakdown of hydrophobic hydration takes placed Note that for this process the volume of activation is small, which implies that the number of water molecules involved in hydration of the reacting system does not change significantly in the activation process. 

We conclude that the beneficial effects of water are not necessarily limited to reactions that are characterised by a negative volume of activation. We infer that, apart from the retro Diels-Alder reaction also other reactions, in which no significant reduction or perhaps even an increase of solvent accessible surface area takes place, can be accelerated by water. A reduction of the nonpolar nature during the activation process is a prerequisite in these cases. 

In the case of the retro Diels-Alder reaction, the nature of the activated complex plays a key role. In the activation process of this transformation, the reaction centre undergoes changes, mainly in the electron distributions, that cause a lowering of the chemical potential of the surrounding water molecules. Most likely, the latter is a consequence of an increased interaction between the reaction centre and the water molecules. Since the enforced hydrophobic effect is entropic in origin, this implies that the orientational constraints of the water molecules in the hydrophobic hydration shell are relieved in the activation process. Hence, it almost seems as if in the activated complex, the hydrocarbon part of the reaction centre is involved in hydrogen bonding interactions. Note that the... 

The type of enforced hydrophobic effect that is operative in the retro Diels-Alder reaction cannot be referred to an enforced hydrophobic interaction, since there is no coming together, but rather a separation of nonpolar molecules during the reaction. It is better to refer to this process as an enforced hydrophobic effect. 

Under different conditions [PdfOAcj2, K2CO3, flu4NBr, NMP], the 1 3 coupling product 86 with 4-aryl-9,10-dihydrophenanthrene units was obtained. The product 86 was transformed into a variety of polycyclic aromatic compounds such as 87 and 88[83], The polycyclic heteroarene-annulated cyclopen-tadicnc 90 is prepared by the coupling of 3-iodopyridine and dicyclopentadiene (89), followed by retro-Diels Alder reaction on thermolysis[84]. 

The reaction of o-iodophenol, norbornadiene and CO proceeds via alkene and CO insertions to afford the lactone 562, which is converted into coumarin (563) by the retro-Diels-Alder reaction. In this coumarin synthesis, norbona-diene behaves as a masked acetylene[4)3],... 

In a novel approach to vitamin K, Hoffmann-La Roche has exploited the potential acidity at C-3 as a means to attach the side chain of vitamin (36). Menadione was reacted with cyclopentadiene to yield the Diels-Alder adduct. The adduct is treated with base and alkylated at C-3 with phytyl chloride. A retro Diels-Alder reaction yields vitamin K. Process improvements in this basic methodology have been claimed by Japanese workers (37). 

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. 

In 1973 two papers appeared almost simultaneously (73T101, 73CPB2026) describing the formation, as a minor product, of 3,4,5-trimethoxycarbonyl-l-phenylpyrazole (346) in the reaction between benzaldehyde phenylhydrazone and DMAD (EC=CE). To account for the formation of (346) George et al. (73T101) proposed a tentative mechanism (Scheme 29) involving a Diels-Alder reaction of type (a Figure 25), followed by a retro-Diels-Alder elimination of methyl phenylpropiolate (347). 

HC(17)1, p. 53), and by retro-Diels-Alder reaction of the adduct from norbornadiene and fulminic acid <67AG(E)456). 

The primary and secondary products of photolysis of common diazirines are collected in Table 4. According to the table secondary reactions include not only isomerization of alkenes and hydrogen elimination to alkynes, but also a retro-Diels-Alder reaction of vibrationally excited cyclohexene, as well as obvious radical reactions in the case of excited propene. 

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]. 

Scheme 9.3. Correlation between for Retro-Diels-Alder Reaction and Resonance Stabilization of Aromatic Products...

These amines gave, with methyl propiolate, products of Michael mono- and bis-addition. Adducts underwent further reaction leading to triazolo[4,5-/]quinolones 181, after retro Diels-Alder reaction and acetylene elimination to its methoxycar-... 

The concept of transient chirality in stereoselective synthesis of five-membered heterocycles using the retro-Diels-Alder methodology 99CRV1163. Five-member heteryladamantanes 99ZOR183. 

Retro Diels-Alder reaction of nitrogen bridgehead compound 415 at 100 °C afforded 6,7,8,9-tetrahydro-4//-pyrido[l,2-u]pyrimidin-4-one and cyclobutadiene (97SC195). 

Although furan is usually a poor diene in the Diels-Alder reaction, the chiral copper reagent 24b promotes its asymmetric addition to acryloyloxazolidinone to afford the 7-oxabicyclo[2.2.1]hept-2-ene derivative in high optical purity (Scheme 1.40). Because a retro-Diels-Alder reaction occurs above -20 °C, the reaction must be performed at low temperature (-78 °C) to obtain a high optical yield. The bicy-... 

R,R-DBFOX/Ph 250 reaction course 303 regioselectivity 216 retro-Diels-Alder reaction 29 reversal of enantioselectivity 224 rhodium... 

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