Fulvenes, Diels-Alder

Oxidation of thiophene with peracid under carefully controlled conditions gives a mixture of thiophene sulfoxide and 2-hydroxythiophene sulfoxide. These compounds are trapped by addition to benzoquinone to give ultimately naphthoquinone (225) and its 5-hydroxy derivative (226) (76ACS(B)353). The further oxidation of the sulfoxide yields the sulfone, which may function as a diene or dienophile in the Diels-Alder reaction (Scheme 88). An azulene synthesis involves the addition of 6-(A,A-dimethylamino)fulvene (227) to a thiophene sulfone (77TL639, 77JA4199). 

The study of the cycloaddition behavior of l,l-dichloro-2-neopentylsilene, C Si =CHCH2Bu (2) [3], reveals the high polarity of the Si=C bond and a strong electrophilicity. The [4+2] cycloaddition reactions with anthracene (3), cyclopentadiene (4) and fulvenes (5) proceed as expected surprising, however, the Diels-Alder reactions with dienes are of lower activity, like naphthalene (6) and furans (7). 

Dimethyl anthracene and diphenyl isobenzofuran form remarkably stable233 cyclopropanone derivatives (353/354), whilst with other diene components (butadiene, tetracyclone, and fulvene) the primarily formed Diels-Alder adducts either suffer ketalizing attack of the solvent (356 - 357, 359 - 358/360) or undergo irreversible changes such as decarbonylation to 362 or rearrangement to 355. 

Hong and coworkers have investigated the cycloaddition chemistry of fulvenes with a wide variety of alkenes and alkynes in great detail [191]. As one example, the reaction of 6,6-dimethylfulvene with benzoquinone is shown in Scheme 6.92. Under microwave conditions in dimethyl sulfoxide (DMSO) at 120 °C, an unusual hetero-[2+3] adduct was formed in 60% yield, the structure of which was determined by X-ray crystallography. The adduct is a structural analogue of the natural products aplysin and pannellin and differs completely from the reported thermal (benzene, 80 °C) Diels-Alder cycloaddition product of the fulvene and benzoquinone (Scheme 6.92) [191]. 

Scheme 6.92 Thermal versus microwave-assisted Diels-Alder cycloaddition reactions of fulvenes with benzoquinones.

Scheme6.241 Azadiene Diels—Alder cycloaddition of fulvenes.

A general hetero-Diels-Alder cycloaddition of fulvenes with azadienes to furnish tetrahydro-[l]pyrindines has been described by Hong and coworkers (Scheme 6.241 see also Scheme 6.92) [424]. A solution of the azadiene and fulvene (1.2 equivalents) precursors in chlorobenzene was heated under open-vessel microwave irradiation for 30 min at 125 °C to provide the target compounds in excellent yields and with exclusive regio- and diastereoselectivity. Performing the reactions under conventional conditions or under microwave irradiation in different solvents provided significantly reduced yields. 

When the cyclic acetylene 260 is generated from a suitable precursor, it undergoes an isomerization reaction spontaneously generating naphthalene (263) and benzo-fulvene (264) as the finally isolable products. Very likely the process begins with a retro-Diels-Alder reaction to the [3]cumulene 261, which in a cascade reaction via the semicydic allene 262 rearranges to 263 and 264 [111]. 

These phenomena can be illustrated by the cycloaddition reactions of fulvenes with electron-deficient a-pyrones. In general, the Diels-Alder reactions of electron-deficient dienes such as 458 with 6-alkyl substituted fulvenes favor addition across one of the endocyclic... 

Niggli and Neuenschwander294 studied the reaction of fulvene (461) with cyclopen-tadiene. The main product fraction consisted of three 1 1 adducts, as illustrated in equation 138. Diels-Alder Adducts 462 and 463 resulted from attack of cyclopentadiene at the endocyclic and exocyclic double bonds of fulvene, respectively. The formation of 464 was rationalized by a [6 + 4] cycloaddition reaction followed by two [1,5] hydrogen shifts. It was stated that due to the absence of electron-donating and electron-withdrawing groups on both triene and diene, fulvene may have reacted via its HOMO as well as its LUMO. 

Nair and coworkers have described the [8 + 2] cycloaddition reactions of 2H-cyclohep-ta[fr]furan-2-ones such as 521 in several reports311. The reactions of 521 with alkenes yield azulene derivatives upon extrusion of carbon dioxide. Table 30 summarizes the results of the reactions between 521 and some 6,6-disubstituted fulvenes 522 (equation 151)311b. In the case of 6,6-dialkyl fulvenes 522a-c, the [8 + 2] cycloadducts 523 were the major adducts obtained, the Diels-Alder adducts 524 only being formed in trace amounts. 

Joining olefin metathesis on the very short list of exchange reactions involving carbon-carbon bonds, the Diels-Alder reaction was studied in 2005 by Lehn and colleagues [52]. As the authors note, most Diels-Alder reactions proceed only in the forward direction at room temperature, with retro Diels-Alder reactions typically requiring elevated temperatures. Careful tuning of the diene and dienophile, however, can alter this significantly. In particular, reactions of substituted fulvenes (32) with diethylcyanofumarate (33) were... 

Figure 1.14 Reversible Diels-Alder reaction of substituted fulvenes with diethy Icyanofumarate.

The Diels-Alder adduct of fulvene and di(2,2,2-trichloroethyl)azodiearboxylate after selective monohydrogenation of the endocyclic pi bond can lead to the bicyclic biscarbamate 107. The electrochemical removal of the TV-protecting carbamoyl groups in a DMF—LiC104—(Hg) system is followed by the oxidation with potassium ferricyanide to give the azo compound 108 which on thermal decomposition forms the linearly fused tricydopentanoid 109 in over 50 % yield (from 107, Scheme 3-41)88a). 

An interesting example of the synthesis of dihydropyrans using hetero Diels-Alder (HD A) methodology is the formation of the polycyclic cage compounds 3 from fulvenes and the tetracyclic enone 2 <06SL3479>. A HDA reaction also features in the synthesis of (+)-8-methoxygoniodiol <06TL4545>. 

Thiophene 1,1-dioxide did not undergo cycloaddition with electron-deficient dienophiles. In most of the cases the dihydrobenzothiophene derivative 109 was obtained as the major product. This shows that self-dimerization is faster than cycloaddition with a different molecule. In the case of dimethyl acetylenedicarboxylate (DMAD) and 4-phenyl-3//-l,2,4-triazole-3,5(4//)-dione (PTAD), the Diels-Alder adducts 111 and 112 of 109 were obtained <1997JA9077>. However, cyclopentadiene gave the Diels-Alder adduct 113 with thiophene 1,1-dioxide. The DMAD adduct 111 on thermolysis undergoes a retro-Diels-Alder reaction to give dimethyl phthalate and thiophene 1,1-dioxide. Azulene was isolated in the thermolysis of 108 in the presence of 6-(dimethylamino)-fulvene this was the result of a [4-1-6] cycloaddition of the thiophene 1,1-dioxide formed in the reaction followed by elimination of SO2 and dimethylamine (Scheme 28) <1999BCJ1919>. 

They react easily with electrophiles and add nucleophiles at C-6. In cycloaddition reactions they may react as 2jt, 4n, or 6 i compounds. According to frontier orbital considerations they readily react with electron-deficient dienophiles (e.g., silenes) in Diels-Alder reactions this is due to the strong interaction between the fulvene HOMO and dienophile LUMO [9]. Although the n and n orbitals of silenes are generally 1-2.5 eV higher in energy than is the case for the alkene congeners [10] a normal [4+2] cycloaddition behaviour for 3 is observed in earlier works [3-5]. 

Interestingly, the reaction of dimethyl fulvene (R = Me) with 2//-azirine 819 in an ultrasonic bath (neat) yielded the alkylation product 825. The stmcture of 825 was unambiguously assigned by single crystal X-ray structure. A possible mechanism to account for the formation of 825 involves an initial [4-1-2] cycloaddition followed by a subsequent rearrangement of the initially formed Diels-Alder cycloadduct 824 (Scheme 204). 

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