Polar cycloaddition

Gothelf presents in Chapter 6 a comprehensive review of metal-catalyzed 1,3-di-polar cycloaddition reactions, with the focus on the properties of different chiral Lewis-acid complexes. The general properties of a chiral aqua complex are presented in the next chapter by Kanamasa, who focuses on 1,3-dipolar cycloaddition reactions of nitrones, nitronates, and diazo compounds. The use of this complex as a highly efficient catalyst for carbo-Diels-Alder reactions and conjugate additions is also described. 

It should also be mentioned that in connection with the investigations on MgX2-BOX catalysts, Desimoni et al. also tested a Zn(C104)2-B0X catalyst for the 1,3-di-polar cycloaddition of a nitrone and acryloyloxazolidinone (see Scheme 6.17). Contrary to the magnesium catalysts, this zinc catalyst was exo selective as an 27 73 exojendo ratio was observed, and 84% ee of the exo isomer was obtained [51]. 

Thiopyrylium ions have been shown to behave as effective dienophiles. Shimizu and co-workers demonstrated that 2-benzothiopyrylium salts undergo [4+2+]-type cationic polar cycloadditions with various 1,3-dienes yield benzo-fused bicyclic sulfonium salts <1994J(P1)3129> (see Section 8.32.2.1.2 of CHEC-II(1996)). However, in this study the authors observed that cycloaddition of 2-benzothiopyrylium salt 40 with 2,3-dimethylbuta-l,3-diene 41a with prolonged reaction times caused a decrease in yield of the cycloadduct 22a (see entries 1 and 2 in Table 5 and Equation 10). In fact, stirring of the reaction mixture for 30 h did not afford the cycloadduct at all, see entry 3, but gave an undetermined complex mixture. 

Table 5 Polar cycloadditions of 2-benzothiopyrylium salt 40 with dimethylbuta-1,3-diene 41a (Equation 10)...

Subsequent, investigation showed that with prolonged reaction times the initially formed cycloadduct 22a then underwent [2+4+]-polar cycloaddition followed by a sequence of rearrangements to afford a novel benzo-fused tricyclic compound 42 (see Equation 11) <1996CC2185>. Various experiments were conducted in order to elucidate the mechanism of the formation of 42. 

Benzothiopyrylium salts have also been shown to undergo [4+2+]-polar cycloadditions with 1,3-dienes in dry 1,2-dichloroethane at room temperature <1996J(P1)2227>. Treatment of 43 with 2,3-dimethylbuta-l,3-diene 41a afforded benzo-fused bicyclic sulfonium salts 22, as shown in Equation (12) and Table 6. The 4-cyano-substituted benzothiopyrylium salt 43d proved to be the most reactive of these substrates (see entry 4). 

Table 7 Polar cycloadditions of 1 -benzothiopyrylium salts 43 with isoprene 41 b (Equation 13)...

Table 8 Polar cycloadditions of 9-thiaphenanthrenium salt 45 with 1,3-butadienes 41 (Equation 14)...

Lactam sulfonium salts bearing a dihydrothiopyran skeleton with a sulfonio bridgehead have been synthesized. Tricyclic benzothiazinium salts 87 were prepared by [4+2+]-polar cycloaddition of a thionium intermediate 99, generated from the corresponding a-chloro sulfide 98, in the presence of silver perchlorate in moderate to good yields (see Equation (28) and Table 17) <1997J(P1)309>. Cycloaddition with isoprene 41b gave adducts 87b and 87c as a... 

Recently, Shimizu reported a novel polar cycloaddition of a 1,2-thiazinylium salt <99TL95>. Compound 175 was generated in situ from the reaction of compound 165 with trifluoroacetic anhydride and lithium tetrafluoroborate. It can undergo a cyclization reaction... 

The 2-thiobenzopyrylium salt 86 behaves as an electron-deficient diene undergoing [4++2] polar cycloadditions with electron-rich alkenes to give the benzo-fused bicyclo[2.2.2]thia-heterocycles 87 (Scheme 59) <00TL2161>. 

The a-methoxylated products are highly useful building blocks for the construction of a carbon-carbon bond a to the trifluoromethyl and diflu-oromethyl groups, which is difficult to obtain by other methods, as shown in Scheme 6.15. Thus, a-tri and a-difluoromethylated a-aminonitriles, which are precursors to the corresponding fluorinated a-amino acids, have been prepared in good yields, and flourinated homoallyanilines have been also successfully prepared [44]. in addition, tri- and difluoromethylated tetra- and dihydroquinoline derivatives can be prepared by cationic polar cycloaddition in high yields [45]. 

The reaction of thioacetyl cations with 2,5-dimethyl-l,5-hexadiene under low-pressure conditions in an FT-ICR mass spectrometer leads to elimination of propene. At variance from the [4 + 2+] polar cycloadditions observed under high-pressure conditions in the QqQqQ instrument, Caserio and coworkers220 invoked electrophilic attack of the CE CS"1"... 

II. Polar Cycloadditions in Which Cationic Aromatic Systems Act as Electrophiles. ... 

IV. Polar Cycloadditions Involving Open-Chain Systems. ... 

The classical 4 + 2 Diels-Alder reaction involves the thermally allowed cycloaddition of an electron-rich (nucleophilic) diene a=b-c=d with an electron-deficient (electrophilic) dienophile e=f. In the polar cycloaddition reactions considered here, the a=b-c=d system bears a positive charge and is so obviously ill-suited for a nucleophilic role that the first examples of polar cycloaddition appeared inexplicable in terms of cycloaddition theory then current. In 1962 Sauer and Wiest demonstrated the existence of a Diels-Alder reaction with inverse electron demand in which the electronic roles of a=b-c=d and e=f are exchanged, with the former becoming the electrophile and the latter... 

In particular, the formal positive charge present in polar cycloaddition would be expected to influence the formation and geometry of intermediate charge-transfer complexes and the electrophilic character of the reaction with alkenes. As will be seen later, these effects result in important influences upon the regio- and stereochemistry as well as the concertedness of polar cycloaddition. 

Professor Richard R. Schmidt appears to have been the first to recognize the existence of a variety of polar 1,4-cycloaddition reactions, the first to so designate them, and the flrst to attempt to create a unifying theory. For the purposes of the present review, the theory suffers chiefly from its inclusion of nonconjugated systems and from its failure to consider what is unquestionably the largest group of polar cycloadditions, those in which the electrophile is of the type C=C-N =C. ... 

Although it is possible to have a polar cycloaddition with a cation containing only carbon and hydrogen, the majority of those which have been found to undergo 1,4-cycloaddition are aromatic quaternary salts. The acridizinium cation (1) used in the first polar cycloaddition reaction of a quaternary salt has been used in the largest number of polar cycloaddition studies to date. The acridizinium ion (1) is particularly suitable for such a study since it is easily prepared, is stable (permitting sealed... 

Note Added in Proof For a more adequate presentation of Dr. R. R. Schmidt s present views on the subject of polar cycloaddition, see Angew. Ghem., Int. Ed. Engl. 12, 212 (1973). 

This first example of the participation of benzyne in a polar cycloaddition gains added importance from two ring-oi>ening reactions which Fields et al. have carried out on the adducts (26). The first is simply thermolysis to afford 9-(2-pyridyl)-anthracene derivatives (27), while the second involves thermolysis of the reduction product of 26, affording anthracene derivatives (28) in excellent yields. 

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