Retro-Diels-Alder route

An attempted synthesis via a retro Diels-Alder route failed, due to the instability of the thiete sulfones at the temperatures required to remove the anthracene blocking group189 (equation 88). 

Dibenzofuro[4,5-c]tropone (8H-dibenzo[a,e]furo[3,4-c]cyclohepten-8-one 368, X = CO) and the corresponding thiepin-5,5-dioxide (8//-dibenzo-[6,/]furo[3,4-retro Diels-Alder reaction exist. The 1-methyl derivative of 368 (X = CO) has been trapped as a maleic anhydride adduct. ... 

Scheme 17.39. (A) Nomenclature (see text) describing charge-remote fragmentation of bile acids (metabolites of cholesterol). (B) Mechanisms of ring cleavage leading to A3, B3, and C3 product ions from negatively charged precursors of bile acids. Lower right shows retro-Diels-Alder route to B3 ion from unsaturated b-ring precursor. (Adapted with permission from Ref. 173.)...

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... 

A somewhat milder route which appears to be devoid of the complications of isomerization is the retro-Diels-Alder reaction of bicyclo [2.2.2] octadienes, frequently substituted with aryl groups (5,30,53,65), [Eq. (2)], and recently Wiberg (88,90) described a very mild route involving both [2 + 2] and [2 + 4] cycloreversions which occur at 60°C to generate Me2Si=C(SiMe3)2. However, the generality of this latter source of silenes has not been established yet [Eq. (3)]. 

Isochromones lose carbon dioxide on heating via retro-Diels-Alder pathway to result in o-quinodimethanes (equation 81)1241,129. An isochromone route to podophyllotoxin derivative has been described (equation 82)130. Diels-Alder adducts of a-pyrone readily extrude carbon dioxide on thermal activation to furnish cyclohexadienes, which are useful substrates in tandem Diels-Alder reactions (equation 83)131. 

The analogous transformation of 125, also realized by flash vacuum pyrolysis, gave rise to allenic oximes 126 [165], which are not directly accessible by the classical route starting from allenyl ketones and hydroxylamine (see Section 7.3.2) [122], Because compounds 125 are prepared from allenyl ketones and furan by [4 + 2]-cycloaddition followed by treatment with hydroxylamine, the retro-Diels-Alder reaction 125 —> 126 is in principle the removal of a protecting group (see also Scheme 7.46). 

For the synthesis of carazostatin (247), the required arylamine 708 was synthesized starting from 1-methoxycyclohexa-l, 3-diene (710) and methyl 2-decynoate (711). The key step in this route is the Diels-Alder cycloaddition of 710 and 711, followed by retro-Diels-Alder reaction with extrusion of ethylene to give 2-heptyl-6-methoxybenzoate (712). Using a three-step sequence, the methoxy-carbonyl group of compound 712 was transformed to the methyl group present in the natural product. 3-Heptyl-3-methylanisole (713) was obtained in 85% overall yield. Finally, the anisole 713 was transformed to the arylamine 708 by nitration and subsequent catalytic hydrogenation. This simple sequence provides the arylamine 708 in six steps and with 26% overall yield (597,598) (Scheme 5.66). 

A stereocontrolled route to the trisubstituted pyrrolidine 146 is achieved using either a concurrent Chugaev-ene reaction or a retro-Diels-Alder-ene reaction <20000L3181, 2001TL4523>, both approaches giving the pyrrolidine in good yields and with complete stereoselectivity. Thus, the thermolysis of either 147 or 148 produces a common intermediate which subsequently undergoes intramolecular ene reaction under the reaction conditions (Scheme 10). 

The retro Diels Alder reaction has also been proved of value in a number of related cases benzo[c]indoles, isobenzofulvenes, furans, and ful-venes have been prepared by the tetrazine route, white the Wiersum-Mijs method has been used for the preparation of benzo[c]indole itself. ... 

As an alternative, copolymerization of alkynes bearing bulky substituents with TCDTF6 (7,8-bis(trifluoromethyl)tricyclo [4.2.2.0 ]deca-3,7,9-triene) was carried out. In the course of this copolymerization, usually referred to as the Durham Route [86-89], the Feast-monomer was introduced into the polymer main chain and subsequently converted into three unsubstituted, conjugated double bonds via a thermally-induced retro-Diels Alder reaction (Scheme 3) [53]. 

The Durham route to polyacetylene 103, 104) involves the metathesis polymerization of 1 to give a soluble but thermally unstable high polymer (Scheme 5.2). Slowly at room temperature, or more rapidly at 80 °C, the polymer undergoes a retro-Diels-Alder reaction. This reaction results in elimination of a substituted benzene and formation of amorphous polyacetylene. An enormous weight loss accompanies the conversion, but high-density films were produced with no apparent voids. The kinetics of the transformation reaction were extensively studied (JOS). 

Scheme 5.3. A revised synthesis of polyacetylene by the Durham route. When 2 is included in the polymer, the conversion to polyacetylene first requires that the diene be generated at 80 °C) before the retro-Diels-Alder reaction...

Further general route to 2-alkyl-2-butenolactones via the retro Diels-Alder reaction was developed. Fig, 5, [23]. Hydrolysis of a known lactone (15), subsequent esterification with diazomethane, and treatment with dihydropyran afforded a stereoisomeric mixture of pyranyl ether. Alkylation of the pyranyl ether with various alkyl halide yielded alkylated products (16). The retro Diels-Alder reaction of 16 was performed by heating at 200-280 C in a sealed tube to give 2-alkyl-2-butenolactones (17). The utility of the butenolactones was demonstrated by the synthesis of hinokinin (18) and dehydrolappaol A dimethyl ether (19). Similarly rather mild, simple synthesis of a-methylene-y-alkylbutyrolactones was deviced using dimethylfulvene as a protective group for the double bond, Fig. 6. [24], The... 

The unparalleled employ of five Diels Alder reactions (3 normal, 2 retro) in the Kende "isobenzofuran" route (Eq.3) provides a fitting conclusion to the discussion of Diels Alder sequences. Although a 1 1 mixture of regiolsomers is produced, the yield of 8c is 17% based on 75a. 

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