Intramolecular Diels-Alder benzynes

The intramolecular Diels-Alder addition of a benzyne to a furan has been exploited in a synthesis of mansonone E (81TL4877). The benzyne (211), generated from the anthranilic acid (210), yields the adduct (212 86%) which is easily converted into the naphthalene (213 Scheme 79). A similar addition was achieved by generating the benzyne by treating an o -dibromobenzene with butyllithium. 

Attachment of a crotonate chain to the alcohol (78), through a mixed carbonate ester, sets up the intramolecular Diels-Alder reaction in the synthesis of podophylotoxin.111 The starting benzocyclobutenol (78) was procured by the sequence of steps shown in Scheme 16. A similar route using a carboxylic ester, in place of the nitrile (76), for the benzyne cyclization gave a mixture of cis- and fra/u-benzocyclo-butenes but ester hydrolysis led to the pure trans acid (77).112... 

A neat intramolecular trap for benzyne works in this way. A standard benzyne-generating reaction—the diazotization of an ortho-amino benzoic acid (Chapter 23) gives a zwitterion that loses nitrogen and CO2 to release the benzyne. A furan tethered to the next ortho position traps the benzyne in an intramolecular Diels-Alder reaction. The yield is impressive and the trap is very efficient. 

Structurally related is biflorin (351), isolated from Capraria biflora, and the first naphtho[l,8-hc]pyranquinone found in nature. It has antibiotic properties. Its structure was determined by Prelog and co-workers (58HCA1386 63HCA409, 63HCA415) and it was synthesized by an intramolecular Diels-Alder addition between a benzyne and furan (86AJC647). 

In a new synthesis of the cyclindrocarine group of alkaloids, it has been shown that when the spirocyclic ammonium ion (99) generated in situ from the amine (97) and the chloroaldehydoester (98) is heated,it generates the intermediate (100) which then undergoes intramolecular Diels-Alder reaction to (101) further elaboration of (101) then produces cyclindrocarine (102).30 The unusual benzyne cycloaddition (103) ... 

One of the early examples of an intramolecular Diels-Alder reaction of benzynes involved cycloaddition to a furan that was tethered to the benzyne moiety . Diazoti-zation of anthranilic acid 669 gave in 86% yield the cycloadduct 670, which was subsequently converted to the o-naphthoquinone 671 (mansonone E 7 steps) as well as to the structurally related mansonones F and I and biflorin. ... 

Benzynes generated by the fluoride-induced elimination of TMS and OTf groups from o-trimethylsilyl [6]- and [7]-heUcenol triflates selectively undergo an intramolecular Diels-Alder reaction with one of the benzene rings within the hehcenes, rather than an external furan molecule, giving rise to bridged derivatives of coro-nene (Equation 12.42) [86). 

Sol 12. (i) The first equivalent of LDA creates an intermediate as a diene component by deprotonation of nitrogen and the second equivalent induces an E2 elimination to generate a benzyne. The intermediate benzyne is then trapped by an intramolecular Diels—Alder reaction to give the enolate, which after protonation and oxidation by air gives the observed aromatic product. 

Benzynes, as dienophiles 13 Bridgehead olefin, formation in the intramolecular Diels-Alder reaction 2, 7 Butressing, effect of, on intramolecular Diels-Alder reaction 41-42... 

Oxazole cycloadditions have been reported with alkyne dienophiles (tandem Diels-Alder addition and retro Diels-Alder loss of a nitrile leads on to furans), benzyne (the primary adduct can be isolated), and with typical alkene dienophiles. The primary adducts from addition of singlet oxygen rearrange, by a mechanism which is not definitely established, to form triamides, themselves useful synthetic intermediates. The only example of this sort of process with an imidazole is an intramolecular example, the product in this case being a pyr-role. ... 

Therefore, it readily undergoes intramolecular hexadehydro-Diels—Alder (HDDA) reaction to give the benzyne intermediate, which is rapidly trapped by the nucleophilic oxygen of the P-silyloxyethyl group. Further migration of the silyl group from oxygen to carbon within zwitterion results in the formation of the Anal product. 

Sol 2. Initial step of the reaction involves an intramolecular hexadehydro-Diels—Alder (HDDA) reaction to give a highly reactive benzyne intermediate. In the absence of external trapping reagents, the benzyne intermediate can simultaneously accept two vicinal hydrogen atoms from a suitable alkane 2H-donor, often the reaction solvent. This desaturates the donor alkane, forming an alkene, and traps the benzyne to a dihydrobenzenoid product... 

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