Dienyl intramolecular Diels-Alder reaction

DFT calculations on the intramolecular Diels-Alder reaction of penta-l,3-dienyl acrylates predict stereoselectivities that are in good agreement with the experimen- (g) tal results.85 Another DFT study at the B3LYP/6-31G(d) level of the intramolecular Diels-Alder cycloaddition of 5-vinylcyclohexa-1,3-dienes has been reported. Reaction rates are influenced by dienophile twisting and substituent effects.86 The intramolecular dehydro-Diels-Alder reactions of ynamides (79) provides a new synthesis of benzo[fc]-, tetrahydrobenzo[fc]-, naphtho[l,2-/j -, and dibenzo[a,c]carbazoles... 

By reaction of the dienal 701 with the dienyl anion 697 and subsequent hydrolysis, the triene 702 was obtained. This enone 702 underwent intramolecular Diels-Alder reaction to give the traws-fused tetrahydroindanone 7031002 (Scheme 182). 

When a similar palladium(0)-catalyzed reaction is performed in an acidic medium at room temperature, i.e. in the presence of acetic acid, different products are formed. These result from a reductive ring cleavage of the methylenecyclopropane (see Section 2.2.2.1. for details) and subsequent intramolecular Diels — Alder reaction with the unsaturated side chain in the case of 5-methylenehept-6-enyl propenoate (5) to ultimately yield 3-oxabicyclo[6.3.1]dodec-8-en-2-one (7). ( )-Octa-5,7-dienyl propenoate (6), however, is stable under the reaction conditions. Product 4, obtained from the acid-free reaction, has thus been proven to be different from the potential products of an isomerization/Diels —Alder addition sequence. 

Intramolecular Diels-Alder reactions have been reported for a series of iV-(hexa-2,4-dienyl) carbamoylindoles, which yield useful tetracyclic systems. Similar cyclizations occur for the related A -acylindoles (CHj replacing NPh), but not for the alkoxycarbonyl analogs (O replacing NPh)... 

The Diels-Alder reaction of ester-tethered trienes is also known as a powerful methodology to construct polycylic Y lactones [68]. Romo et al. [69] surveyed effective organic nucleophilic catalysts for tandem intermolecular Diels-Alder reaction/lactonization reaction of achiral a, 3-unsaturated acid chlorides with dienyl alcohol 100 (Scheme 45). In this case, when chiral Lewis base 102 was used as a nucleophilic catalyst, excellent enantioselectivity was realized. Lipase-catalyzed domino kinetic resolution/intramolecular Diels-Alder reaction of furfuryl alcohols with acrylic acids was also carried out by Akai and Kita [70]. 

Another intramolecular version of the aza-Diels-Alder reaction was realized with the condensation of a dienyl aldehyde and benzylamine hydrochloride at 70 °C in 50% aqueous ethanol (Scheme 10) [59]. This methodology was used in the synthesis of racemic dihydrocannivonine [60] and substituted octahydro-quinolines related to pumiliotoxin C [61]. 

A boron-tethered (C-B-O) intramolecular Diels-Alder (IMDA) approach has been used to prepare cyclic alkenyl boronic esters 140 (Scheme 19). Thus, reaction of 2equiv of the dienyl alcohol 138 with 137 in THF, in the presence of molecular sieves, provides the corresponding IMDA precursors 139. The IMDS reaction was then accomplished at 190 °C in a toluene solution, with 5 mol% of 2,6-di-fer7-butyl-4-methylphenol as a free radical inhibitor. Transformation of the carbon-boron bond in 140, using standard organoborane reactions, can then afford a variety of functionalized cyclohexene derivatives <1999JA450>. 

Grieco et al. have also probed an intramolecular variant of the iminium reaction with cyclohexadiene [19]. The intramolecular cyclization of cyclo-hexadienyl aldehyde 45 provides the precursor to dihydrocannivonine 46. Initial attempts to execute the intramolecular iminium-ion Diels-Alder reaction under standard conditions gave rise to poor yields (<10%), probably due to the inherent instability of dienyl aldehyde 45. Yields are dramatically improved by slow addition of a solution of 45 in ethanol over 20-30 h to monomethylamine hydrochloride in aqueous ethanol at 70°C. This modified protocol results in a 66% yield of tricyclic amine 46. Subsequent hydrogenation of 46 affords racemic dihydrocannivonine 47 ... 

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