Cycloaddition of o-quinodimethane

In a recent re-examination of the thermolysis of benzocyclobutenes for the in situ generation of o-quinodimethanes, the resultant IMDA diastereoselectivity was highly dependent on the nature of the hydroxyl protective group.90 The intramolecular 4 + 2-cycloaddition of o-quinodimethanes (83), derived from ene-bis(sulfinylallenes) (82), with electron-deficient and electron-rich alkenes produced the corresponding polycyclic aromatic compounds (84) (Scheme 22).91 The enantioselective Diels-Alder... 

Iminyl radicals, formation of N-heterocycles from 78YGK368. Intramolecular cycloaddition of o-quinodimethanes in synthesis of bi- and... 

Intramolecular cycloadditions of o-quinodimethanes (144), generated thermally from (145), are useful in the preparation of some polycyclic nitrogen-containing compounds, e.g. (146). ... 

Several additional illustrations of the use of intramolecular cycloadditions of o-quinodimethane intermediates in the synthesis of steroidal molecules have been published by Kametani and co-workers. ... 

The synthetic utility of o-quinodimethane generated by cheletropic elimination of S02 has been amply demonstrated by Oppolzer and Nicolaou, who have conducted an intramolecular cycloaddition coupled with the alkylation of 1,3-dihydrobenzo[c]thiophene 2,2-dioxide122. When 1,3-dihydro-l-(4-pentenyl)benzo[c]thiophene 2,2-dioxide (201) prepared from 1,3-dihydrobenzo[c]thiophene 2,2-dioxide and 4-pentenyl bromide is heated in di-n-butyl... 

The synthetic utility of o-quinodimethane generated by cheletropic elimination of SO2 has been amply demonstrated by Oppolzer and Nicolaou, who have conducted an intramolecular cycloaddition coupled with the alkylation... 

These cycloadditions with o-quinodimethanes provide a broad variety of useful fullerene functionalizations, since o-quinodimethanes can be prepared using several routes and the resulting cycloadducts are thermally stable [42], There exist several alternatives to the iodide-induced bromine 1,4-elimination of 1,2-bis (bromomethyl)-benzenes [44-47]. o-Quinodimethanes have been prepared by thermolysis of 3-isochromanone (42) [43], benzocyclobutenes (43) [48-50], isobenzothiophene 2,2-dioxides (44) [42] and sultines [51,52] or by photolysis of o-alkylphenones such as 45 [53-55] and could be added to Cjq in good yields (Scheme 4.7). Indene, thermally rearranged to isoindene, also adds to Cjq in similar fashion to quinodimethanes [56]. 

O-Quinodimethanes. A recent simple synthesis of Al") 5(lu)-estratriene-l 7-one (5)2 is based on the fact that on pyrolysis substances such as 1 lose sulfur dioxide with generation of o-quinodimethanes.1 The anion of 1 is generated most satisfactorily with KH (1.1 equivalent) in DMF. at 0°. It can be converted predominately to monoalkylated products, particularly if an excess of the anion is used. Thus reaction of the anion of 1 with 2 results in the diastereoisomers 3 and 4. After deketalization, the corresponding ketones are heated at 210" for 8 hours. The o-quinodimethane (a) is formed and undergoes intramolecular cycloaddition to form 5. 

A major initial limitation of the benzocyclobutene approach to o-quinodimethanes was the lack of efficient, large-scale syntheses for many specifically substituted derivatives. Fortunately, recent developments have lemov much of this impediment. Q>nceptually, the synthesis of benzocyclobutenes from aromatic precursors can be envisaged in only a limited number of ways. These include [2 -i- 2] cycloadditions involving benzynes and alkenes, intramolecular cyclization on to a benzyne, cyclizations involving arene anions, and electrocyclic closure of o-quinodimethanes. Benzocyclobutene derivatives can also be prepared by aromatization of bicyclo[4.2.0]octanes. Detailed discussion of variations to these approaches can be found in the cited reviews. The cobalt catalyzed co-oligomerization of 1,5-hexadiynes with al-kynes, especially bis(trimethylsilyl)acetylene, has also been employed for the preparation of specifically substituted benzocyclobutenes. In the latter case the cyclobutenes are often not isolated but converted directly to o-quinodimethanes and subsequent products. ... 

W. Oppolzer, Synthesis, 793 (1978), has reviewed intramolecular cycloaddition reactions of o-quinodimethanes. 

Scheme 2.11. Determination of the rate constants of the cycloaddition reaction of o-quinodimethane based on the product analysis depending on the delay time between the first 248-nm laser irradiation and second 308-nm laser irradiation. o-Quinodimethane was generated by the first 248-nm laser pulse irradiation. The cycloaddition reaction with maleic anhydride (path 1 with the rate constant of k ) and the dimerization (path 2 with the bulk rate constant of k2) were quenched by the photochemical conversion of o-quinodimethane into benzocyclobutene with the second 308-nm laser pulse irradiation.

The cycloaddition of heterocyclic rr-quinodimethanes to buckminsterfullerene (Coo) can be regarded as a special case of the Dieks-Alder reaction cycloadducts with the general structure 14 are obtained. This type of cycloaddition has been reported with a wide range of o-quinodimethanes <96MI1, 96JCS(P1)1077, 97TL2557, 97T9075>. 

Following earlier application of o-quinodimethane cycloaddition methodology to the alkaloid field, Oppolzer s initially described approach to steroids involved the reaction 93 94, which apparently has not been described in detail. ... 

The extrusion of SO2 from heteroaromatic-fused 3-sulfolenes has been successfully used as a general strategy for the synthesis of a variety of o-quinodimethane derivatives [137]. This synthetic approach is quite attractive due to the relative ease with which the sulfolenes are prepared, as well as the stability of these versatile precursors. Under thermal conditions (150°C), indolo-3-sulfolenes 417a-b readily produce the quinodimethane intermediates 418a-b, which then undergo Diels-Alder cycloaddition reactions with A-phenylmaleimide (220) to produce the [4-1-21-cycloadducts 419a-b in good yields (Scheme 95) [138]. 

Based on these results, we postulated the formation of o-quinodimethanes from homophthalic anhydrides. At this time, the proper dienophile exists in the reaction mixture, and the cycloaddition reaction would produce the peri-hydroxyl aromatic compound by decarboxylation of the first adduct. We first heated the mixture of homophthahc anhydride 7 and benzoquinone 8. Although heating the mixture did not give the cycloadduct product at all, a long reaction time in a sealed tube afforded the coupled product 9 in low yield. The reactivity of the homophthalic anhydrides was significantly enhanced by treatment with base, such as LDA or NaH. Thus the reaction in the presence of NaH proceeded at low temperature with a short reaction time to give the coupled product 9 in high yield (Scheme 3) [13-15]. 

A further report on a [ r -1- tttt]-cycloaddition of a diene and SO2 has appeared " the reaction of o-quinodimethane with SOj afforded mainly the cyclic sulphinate (182), and only small amounts of the [n -1- nn] product were formed. 

In o-quinodimethane derivatives the dienes are in the c -configuration, which allows ready cycloaddition reactions with phenyl isocyanate. For example, phenylimines of o-quinodimethanes 461 afford the quinazolinediones 462 on reaction with phenyl isocyanate followed by hydrolysis... 

Bis-o-quinodimethanes have also been used to functionalize [60]-fullerene by Diels Alder reaction. An example is the preparation of main-chain polymers with incorporated [60]-fullerene units [48] illustrated in Scheme 2.20. Cycloaddition of bis-diene 50 generated in situ from bis-sulfone 49 with [60]-fullerene leads to an oligomer mixture 51. Another type of functionalization is based on the... 

The o-quinodimethanes are very reactive, unstable dienes, which are usually prepared in situ. The cycloaddition under high pressure of the dibromo-o-quinodimethane 91, generated in situ from a,a,a, a -tetrabromo-o-xylene. 

The forerunner in the Co-catalyzed [2+2+2] cycloaddition domino processes was that identified by Vollhardt and colleagues [273], with their excellent synthesis of steroids. Reaction of 6/4-1 with [CpCo(CO)2] gave compound 6/4-3 with an aromatic ring B via the intermediate 6/4-2. In this process, trimerization of the three alkyne moieties first takes place, and this is followed by an electrocyclic ring opening of the formed cyclobutene to give o-quinodimethane. This then undergoes a Diels-Alder reaction to provide the steroid 6/4-3 (Scheme 6/4.1). 

Cycloadditions selectively afford the adducts on the 6,6-ring junctions [65], and the products occasionally undergo a facile retro-Diels-Alder reaction as a consequence of the low thermodynamic stability of the adduct. Very stable Diels-Alder cycloadducts have, however, been prepared by use of different substituted o-quinodimethanes, probably because of stabilization by aromatization of the resulting adducts [66],... 

---