Diels-Alder reactions cyclisations

Problem The synthesis of bicycllc lactone (25) by the acid-catalysed cyclisation of (24) could be tried if (23) can be made by via Diels-Alder reaction. 

It is easier to use maleic anhydride for the Diels-Alder reaction and hydrolyse to (41) before cyclising to (39) in strong acid. 

Dienes, 11 addition to, 194-198 cisoid conformation, 197, 350 conjugated, 11 Cope rearrangement, 354 cyclisation, 346 cycloaddition to, 348 Diels-Alder reaction, 197, 349 excited state, 13 heat of hydrogenation, 16,194 isolated, 11 m.o.s of, 12 polymerisation, 323 Dienone intermediates, 356 Dienone/phenol rearrangement, 115 Dienophiles, 198, 350 Digonal hybridisation, 5 Dimedone, 202 Dimroth s Ej- parameter, 391 solvatochromic shifts, 391 solvent polarity, 391 Y and,392 Dinitrofluorobenzene proteins and, 172... 

Exo cyclisations of vinyllithiums onto phenyl-substituted alkynes 392 and 394 are also syn stereospecific, and give the sort of stereodefined dienes 393 and 395 of value in Diels Alder reactions.180 6-Exo cyclisations are also possible but are much slower, though they still give geometrically pure products (in contrast to 6-exo cyclisations onto silyl alkynes see below). Vinyllithiums cyclise onto alkyl-substituted alkynes (such as 396) only in the presence of TMEDA, and they do so very slowly. Nonetheless, a single geometrical isomer of the product 397 is obtained. 

Very recently, chiral tricarbonylchromium complexes have been introduced as novel chiral auxiliaries for aza Diels-Alder reactions [192, 193]. Using the brominated imine 3-8, Kiindig s group was successful in efficiently generating enantiopure polycyclic compounds such as 3-10 by cycloaddition of 3-8 to l-methoxy-3-trimethylsilyloxy-l,3-butadiene (Danishefsky s diene), subsequent radical cyclisation of the cycloadduct 3-9 and oxidative metal removal from 3-11 (Fig. 3-3). 

CL128>. Based on a Diels-Alder reaction between a 2-bromobenzoquinone and a 2-methylbutadiene and a subsequent base-promoted ynone cyclisation, the anthra[l,2-b]pyran-4,7,12-trione system 33 has been synthesised <06AG(E)6990> and the methodology used in an enantioselective total synthesis of the pluramycin antibiotic, y-indomycinone <06OL5873>. 

The intramolecular Diels-Alder reactions involving boryl-3-propenoic acid derivatives has been addressed to. So, heating the trienylamide (7) at 80°C in toluene for 15 hours led to a 1/3 mixture of the cycloadducts (8) and (8 ) isolated in 72 % yield (figure 6) l7. The trienylamide (9) could not be isolated since the IMDA occured at the temperature of the coupling step, i,e below 0°C in ether for 30 minutes. This very fast cyclisation led to a 85/15 mixture of cycloadducts (10) and (10 ) having respectively a cis and trans junction in the bicyclic structure. The cis bicyclic structure (10) results from an endo approach of the diene and the dienophile. This is in agreement with literature data l8. 

Most asymmetric Diels-Alder reactions have the chiral auxiliary attached to the dienophile as in the example we have just seen.14 One of the earliest was the blocked a-hydroxyenone16 136 that cyclises with electron-rich dienes to give adducts such as 139 and was used in a synthesis of pumiliotoxin 143 based on that of Overman.17 The weakness here is the cleavage of the auxiliary requires reduction to a diol and periodate cleavage with the inevitable destruction of the auxiliary. 

Three enantiomerically pure starting materials ensure remote stereochemical control Tandem iminium ion formation and vinyl silane cyclisation Part IV - Tandem Pericyclic Reactions Electrocyclic Formation of a Diene for Diels-Alder Reaction Tandem Ene Reactions Tandem [3,3]-Sigmatropic Rearrangements Tandem Aza-Diels-Alder and Aza-Ene Reactions... 

Cycloadditions only proceeding after electron transfer activation via the radical cation of one partner are illustrated by the final examples. According to K. Mizono various bis-enolethers tethered by long chains (polyether or alkyl) can be cyclisized to bicyclic cyclobutanes using electron transfer sensitizer like dicyanonaphthalene or dicyano-anthracene. Note that this type of dimerization starting from enol ethers are not possible under triplet sensitization or by direct irradiation. Only the intramolecular cyclization ci the silane-bridged 2>. s-styrene can be carried out under direct photolysis. E. Steckhan made use of this procedure to perform an intermolecular [4+2] cycloaddition of indole to a chiral 1,3-cyclohexadiene. He has used successfully the sensitizer triphenylpyrylium salt in many examples. Here, the reaction follows a general course which has been developed Bauld and which may be called "hole catalyzed Diels-Alder reaction". 

Diels Alder reaction, and to some spiro-ketones by cyclisation of 91... 

Ring aromatic steroids (72) have been constructed by sequential cobalt-catalysed cyclisation of enetriynes (69), and intramolecular Diels-Alder reaction of the resulting o-quinodimethanes (71) derived... 

A Diels-Alder reaction features in two approaches to the cannabinoid nucleus. A quinone methide is postulated in the intramolecular HDA cyclisation of (30) to (31) <97CC1867>, whilst an oxazoline-Cu(lI) complex imparts high enantioselectivity to the formation of the Al-THC precursor (32) <97TL3193>. 

The allene ether (28) cyclises to the benzoxepine (29) on treatment with PdCl2(PPh3)2 at 100 °C <94JOC4730>. The product will undergo Diels-Alder reactions giving access to further fused derivatives (Scheme 7). 

In the synthesis of (-l-)-Minfiensine by MaeMillan and coworkers, a novel Diels-Alder/amine cyclisation sequenee is aehieved using n with TBA (tri-bromoacetic acid) as the coeatalyst, allowing the synthesis of the complex tetracyclic pyrrolindoline core of the target molecule (87% yield, 96% ee), with low loadings possible (5 mol%). Similarly, MacMillan and coworkers have described the short nine-step synthesis of (—)-Vincorine, in which they employ the catalyst II and HBF4 as a cocatalyst for the formation of three stereocentres with the correet absolute and relative stereochemistry. The combination of an intermolecular Diels-Alder reaction with an iminium cyclisation cascade allowed formation of the tetracyclic alkaloid core in one step (70% yield, 95% ee). ... 

An outstanding example of a branching pathway exploited complementary cyclisation reactions to yield alternative molecular scaffolds (Scheme 1.5). A four-component Petasis condensation reaction was used to assemble flexible cyclisation precursors e.g. 14). Alternative cyclisation reactions were then used to yield products with distinct molecular scaffolds Pd-catalysed cyclisation (- 15a) enyne metathesis (- 15b) Ru-catalysed cycloheptatriene formation (- 15c) Au-catalysed cyclisation of the alcohol onto the alkyne (- 15d) base-induced cyclisation (- 15e) Pauson-Khand reaction 15f) and Miesenheimer [ 2,3]-sigmatropic rearrangement (not shown). Four of these cyclisation reactions could be used again to convert the enyne 15e into molecules with four further scaffolds (17a-d). In addition, Diels Alder reactions with 4-methyl-l,2,4-triazoline-3,5-dione converted the dienes 15b, 17a and 17d... 

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