NOCAS process

The best-known reactions belonging to this class are based either on the photo-NOCAS process [32] or on the photochemistry of Barton esters [69]. In the first case, a three-component reaction involving a cyanoarene, an olefin, and a nucleophile (usually the solvent) occurs. The reaction is generally initiated by a PET process between the aromatic and the olefin. The examples presented below are chosen from among the most representative and most recent. A typical reaction is illustrated in Scheme 3.26, where an enolized P-dicarbonyl compound acts as an added nucleophile. 

In the examples above, the attacking radical arises from the fragmentation of the radical cation, but, as already noted, in the presence of a nucleophile, radicals are also formed by addition to olefinic (Scheme 4) [45,78-79], aromatic [80] or heterocyclic [81] radical cations, and react in the same way. For the reactions involving alkenes the acronym Nucleophile-Olefin Combination Aromatic Substitution (NOCAS process) has been proposed in this process, the radical cation of strained alkenes may rearrange before addition (Scheme 20) [79]. 

As can be seen from the few examples cited above SET processes are now fairly common in organic photochemistry. One of the areas where considerable study has taken place is the process referred to as a photo-NOCAS. Within this framework Albini and coworkers have shown that the products formed from the reaction of 2,3-dimethylbut-2-ene with 1,4-dicyanobenzene are compounds (22)- 25). The reaction was brought about using phenanthrene as the initial light absorber. This technique leads to cleaner reactions than those where the 1,4-dicyanobenzene is irradiated directly. The solvent system used is methanol/ acetonitrile and products (24) and (25) are the result of solvent incorporation. A further example of photo-NOCAS chemistry has been reported by Arnold and coworkers.Typical of the examples studied is the reaction illustrated in Scheme 2. The cyclization of the dienes (26) was also examined. This specific example deals with the generation of radical cations from (/ )-(+)-a-terpineol and (/ )-(+)-limonene with 1,4-dicyanobenzene as the electron accepting sensitizer. In another detailed study on reactions of this type the factors that control the regiochemistry in photo-NOCAS processes have been assessed. ... 

The photo-NOCAS process has also been reported with P-myrcene (57) as the reactant. The resultant radical cation, generated using dicyanobenzene as the sensitiser, affords the five products (58-62) shown and cyclization within the myrcene radical cation is an essential feature of this reaction sequence. SET photochemistry of aliphatic electron donors can provide a source of radicals. Thus irradiation of donors such as (63), (64), (65) and (66) results in bond fission and the formation of alkyl radicals which undergo addition to alkenes e.g. 67) or alkynes e.g. 68) to give the adducts (69) and (70), respectively. ... 

Other studies have sought to establish the scope and limitations of the photo-NOCAS process. Thus Arnold and co-workers have examined the reactions of alkenes with 1,4-dicyanobenzene (DCB). A typical result from this reaction is shown in Scheme 1. All of the products arise from the attack of the radical cation of the alkene on the DCB sensitizer with loss of the cyano function. A further study of photo-NOCAS reactivity has demonstrated that the radical cation of 2,3-dimethylbut-2-ene, formed by irradiation in the presence of DCB/biphenyl, can be trapped by fluoride ion. The resultant radical (39) reacts with the radical anion of DCB to yield the adduct (40). The radical cation of methylenecyclopro-pane (41) can be formed by irradiation in the presence of DCB as the sensitizer. The products are illustrated in Scheme 2 and, as shown, in all cases the cyclopropane ring remains intact. The diene (42) undergoes SET to dicyanoben-zene as the sensitizer with biphenyl as the co-sensitizer. In the absence of nucleophiles many products are formed such as (43) and (44) by reaction with the solvent acetonitrile or the sensitizer, respectively. In the presence of alcohols low yields of (45) and (46) are formed by reaction of the alcohol with the radical cation of the diene (42). 

A further variation of these functionalizations of cyanoarenes is the NOCAS process [14, 15]. As shown in Scheme 14.2, path g, this involves the addition of a nucleophile (which is often the solvent) to the donor radical cation. The thus-formed neutral radical adds to the acceptor radical anion, while rearomatization by the loss of an anion leads again to an overall ipso-substitution. AUenes could be used as the donors in these reactions, as shown recently by Arnold [50]. Accordingly, the irradiation of TCB in the presence of tetramethylaUene (15) in a 3 1 MeCN/MeOH mixture afforded 1 1 1 arene-allene-methanol adduct 16 in 48% yield (Scheme 14.9, central part). Interestingly, the addition of methanol took place exclusively at the central allene carbon, while aromatic substitution occurred through the terminal carbons. co-Alkenols, in which an O-nucleophile and an easily oxidized moiety are both present, could also be used. In the latter case, the initial ET was followed by a cyclization, yielding aryl-substituted tetra-hydrofurans or tetrahydropyrans as the final products via a tandem Ar—C, C—O bond formation [51]. 

Another three components synthesis is involved in the extensively investigated NOCAS process (nucleophile olefin combination aromatic substitution, path h) [89,90], In this case, a nucleophile adds to an alkene radical cation and again the interaction between the resulting radical and the radical anion of the aromatic nitrile may follow two paths. The first is electron transfer, which results in sensitized anti-Markovnikov addition onto the alkene, and is favored with stabilized, reducible radicals such as the benzyl radicals obtained from aryl olefins. The latter one is... 

The NOCAS process has been extended to conjngated [99] and nonconjugated dienes (in the latter case a ring may be formed, see Scheme4.15) [1(X),101 ], to alkenols (where the intramolecular trapping by the hydroxyl group replaces intermolecular alcohol addition) [102,103] and to allenes [104],... 

The presence of hetero-atoms within the system, remote from the alkene double bonds, does not have an adverse influence on the SET processes that occur. Thus irradiation of the diene 33 in benzene solution with 1,4-dicyanonaphthalene as the electron-transfer sensitizer affords the cyclobutane 34 in 78% yield. Various examples of the reaction were described giving cyclobutane derivatives in 54-69% yield. Benzene, or an arene solvent, is vital for the success of the reaction. When acetonitrile is used, allylation of the sensitizer (akin to the photo-NOCAS reaction) results in the formation of the three products 35-3718. (2 + 2)-Cyclization of this type described for 33 is also seen with the dialkenyl ether 38. When 38 is irradiated using X > 350 nm or X > 450 nm in acetonitrile... 

Electron Transfer Processes - A single electron-transfer mechanism is involved in the cycloaddition of alkenes, such as 2-methylpropene, to 1,2-dicyanonaphthalene. Reaction of the alkene radical cation with the radical anion of the sensitiser results in the products shown in the Scheme 1. Incorporation of solvent to give (55) occurs as one of the main products in addition to what are essentially photo-NOCAS products (56). 

When the radical cation DX does not undergo fragmentation, as is typical when arising from an olefin, an alternative is found in the attack by a nucleophile Nu". The resulting radical X-D-Nu couples with the aryl radical anion ArZ " and regains aromaticity, yielding again a three-components adduct X-ArD-Nu [the NOCAS (Nucleophile Olefin Combination Aromatic Substitution) process, as shown in Scheme 14.2, path g [14, 15]. In Scheme 14.2, the aromatic compound... 

Strained donor and a NOCAS-type photosubstitution process has been obtained also from a saturated donor such as tricyclene (Scheme 4.16) [105,106],... 

Solvent addition to the alkene radical cation is often preferred to fragmentation in nucleophilic media such as alcohols (this gives rise to another useful photosubstitution process on aromatics, the photo-NOCAS reaction discussed elsewhere in this Handbook). 

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