Nitriles oxetanes

Head-to-head [2+2]photocycloaddition of 1,2-diarylethanediones and 2-aminopropene nitriles (CH2 C(CN)NR2) occurs to yield oxetanes 10 in moderate to good yields. The formation of only one diastereoisomer in each of the cases investigated is rationalized in terms of the most easily accessible and stabilized 1,4-diradical intermediate <95RTC498>. 2,3,4-Trisubstituted oxetanes 11 are obtained in high yield by intramolecular nucleophilic attack of the anion from certain 2-(l-alkoxyethyl)-3-substituted oxiranes <96JOC4466>. 

The synthesis of nitrogen containing heterocyclic systems by photocylo-addition processes is virtually limited to examples involving [ 2 + 2] cycloaddition of imines, nitriles, and azo compounds. Successful additions are few in number and the requirements for success uncertain. The reactions do not proceed with the facility with which carbonyl containing compounds undergo photocycloaddition to alkenes to give oxetans, and various explanations have been advanced to account for this observed lack of reactivity.226... 

The sulfuric acid-catalyzed condensation of oxetanes with nitriles gives dihydro-1,3-oxazines (45). This reaction has been reported for a wide variety of 2,2-disubstituted oxetanes and nitriles, generally giving fair yields (74ZOR95, 82ZOR181). The nitrogen atom of the nitrile always bonds to the more substituted a-carbon of the oxetane. 

This type of reaction has some precedence i.e., cyanohydrin formation (KCN, DMSO), followed by intramolecular displacement of a tosylate by the incipient alkoxide leads to the formation of a 2-cyano oxetane system. Furthermore, KCN in MeOH results in the addition of methanol across a nitrile group. Nerdel, F. Weyerstahl, P. Lucas, K. Tetrahedron Lett. 1965, 5751. 

In all cases, the cyclic amino substituent in the major diastereoisomer is oriented cis to the aryl moiety of the participating aroyl group whereas the nonparticipating aroyl group is cis to the nitrile function. Whereas 2-naphthyl-substituted diones from oxetanes, 1,1 -naphthyl- and 1-(1-naphthyl)-2-phenyl ethanedione are unreactive. The latter effect probably reflects the nn nature of the lowest excited triplet state of these diones. 

No attack at C-5 leading to the oxetane (3,5-anhydro) has been noted [1]. Enzymatic cycliza-tion of the a,/3-unsaturated sugar nitrile provided the corresponding 3,6-anhydro-glucofura-nose derivative in good yield [1] (O Fig. 18). 

The reaction of epoxides, nitriles and sulfuric acid results in generally poor yields of oxazoline derivatives, and mixtures of isomers may also result (Scheme 28)." These difficulties are overcome by the use of epoxy ethers (equation 35). As shown in equation (36), oxetanes undergo analogous reactions to afford dihydro-1,3-oxazines in excellent quantities. ... 

Most interest in this area centers around 5,6-dihydro-4//-l,3-oxazines. These compounds can be prepared in a variety of ways, for example, by the addition of nitriles to oxetanes (presumably the latter ring-open by 5n1 cleavage, prior to reaction with the nitrile (Equation (13)) <8iTL34l, 82ZOR178), or through the interaction of -hydroxyalkenes with nitriles in the presence of concentrated sulfuric acid (Equation (14)) <79URP649713>. 

Amongst the few reported reactions of oxetans is their non-stereospecific conversion into oxazines when treated with nitriles and the reaction of the (R)-lactone (44) with a Grignard reagent as the key step in a novel synthesis of (i ,/ )-phytol. ... 

A mixture of the oxetan (26) and olefin dimer is obtained from the photolysis of ajS-unsaturated nitriles and aliphatic ketones. Oxetan formation... 

Reactions with Oxiranes, Oxetanes, and Aziridines. Lewis acids, lanthanide salts, and titanium tetraisopropoxide or aluminum isopropoxide catalyze the reactions of cyanotri-methylsilane with oxiranes, oxetanes, and aziridines, yielding ring-opened products. The nature of the products and the regio-selectivity of the reaction are primarily dependent on the nature of the Lewis acid, the substitution pattern in the substrate, and the reaction conditions. Monosubstituted oxiranes undergo regiospe-cific cleavage to form 3-(trimethylsiloxy)nitriles when refluxed with a slight excess of cyanotrimethylsilane in the presence of a catalytic amount of potassium cyanide-18-crown-6 complex (eqs 8-10). The addition of cyanide occurs exclusively at the least-substituted carbon. 

The ambident nature of cyanotrimethylsilane can lead to the formation of nitriles or isocyanides, depending on the nature of the catalyst. For example, cyanotrimethylsilane reactions with epoxides and oxetanes catalyzed by soft Lewis acids give rise to 2-(trimethylsiloxy) isocyanides arising by attack on the more substituted carbon (eqs 15 and 16).Milder reaction conditions and better yields of isocyanides can be realized when the reaction of cyanotrimethylsilane with oxiranes is carried out in the presence of Pd(CN)2, SnCL, or MesGa (eq 17). Isocyanides are useful precursors for the synthesis of /3-amino alcohols and oxazolines. 

Another photoreaction between ketones and olefins or dienes, which has often been connected to the involvement of exciplexes, is the Patemo-Biichi reaction [4,5], i.e., the photocycloaddition of C=C double bonds to carbonyl C=0 bonds under formation of oxetanes [17,78,207-217], Especially for electron-rich olefins such as ethyl vinyl ether or 1,2-diethoxyethylene, intermediary exciplexes have often been postulated [212], with the consequence of a diminished legioselectivity and stereospecificity for oxetane formation. On the other hand, electron-deficient olefins such as a,P-unsaturated nitriles react with a high legioselectivity and stereospedlicity due to a well defined transition state, which is based on the electronic leqniranents of n,7t -excited ketones [17]. 

Hydrogen autotransfer has been shown to tolerate a wide range of functional groups, including esters, ethers, tertiary amines, aryl chlorides, aryl bromides, aryl iodides, ketals, nitroarenes, nitriles, and oxetanes. Notably, Williams reported a series of amine alleviations with alcohols in the presence of boronic esters which could be present in either the alcohol or amine starting material (Scheme 12.9). °... 

The Patemo-Biichi reaction of 5-substituted adamantan-2-ones 55 with fumaro-nitrile to form oxetanes 56 and 57 (Scheme 20) has been studied by Turro and coworkers [93,94]. In the CD-free photocycloaddition performed in acetonitrile or water, the antf-oxetane 56 formed through the 5jn-face attack of fumaronitrile is slightly favored, with the 57/56 ratio varying from 47/53 to 36/64. When the photocycloaddition reaction is carried out in the presence of -CD in aqueous solution, the stereochemical preference is switched to 5jn-oxetane 57 and the... 

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