Norrish-Yang reaction

The Norrish-Yang reaction [20] is based on the photochemical excitation of ketones followed by an intramolecular hydrogen transfer with the formation of biradicals. Wessig and coworkers used this procedure to prepare functionalized cyclopropyl ketones as 5-75 from 5-72 (Scheme 5.15) [21]. The substrate employed con-... 

Starting from the Pt-cinchona modified system, more recently an interesting concept has been developed by Feast and coworkers [144], A chiral acidic zeolite was created by loading one molecule of iM,3-dithianc-l-oxide per supercage of zeolite Y, either during or after the zeolite synthesis. Other chiral zeolites were formed by adsorbing ephedrine as a modifier on zeolites X and Y for the Norrish-Yang reaction [145],... 

The synthesis of l,3-oxazin-4-ones of type 464 is the first example of the formation of a C-O bond in the course of the Norrish-Yang reaction. Upon treatment with 1-hydroxy-l-phenyl-A -iodanyl mesylate, /3-keto amide 460 was converted to the corresponding a-mesyloxy-/3-keto amide 461 in excellent yield. On ultraviolet (UV) irradiation (A>300nm) of 461, 5-hydrogen transfer to the excited carbonyl group occurred and the diradical 462 thus formed underwent MsOH elimination to enolate diradical 463, cyclization of which resulted in formation of 3-methyl-6-phenyl-3,4-dihydro-277-l,3-oxazin-4-one 464 (Scheme 89) <2001S1258>. 

Stereoselective Photocydization of Ketones (Norrish-Yang Reaction)... 

Depending on the linking group X, a variety of carbo- and heterocydic compounds has been prepared by means of the Norrish-Yang reaction [3]. Accordingly, cydopropanes, cydobutanes (the Yang reaction in the narrow sense), azeti-... 

Scheme 1. General principle of the Norrish-Yang reaction.

The complex reaction mechanism of the Norrish-Yang reaction has been discussed in several reviews [3], Here, only the most important mechanistic cornerstones will be mentioned. The following aspects will be addressed ... 

There are still two other factors influencing the reactivity of ketones in the Norrish-Yang reaction. If functional groups with a relatively low oxidation potential (amino, alkenyl or aryl groups, thioethers) are present in the reactants, the excited state may be quenched by partial or complete charge transfer from these groups to the extited carbonyl group. The effects of such processes may vary from a complete loss of reactivity to an entirely new reaction mode - cyclization reactions ini-... 

Mechanistic remarks relating to the regioselectivity may be subdivided in three parts. The first deals with concepts within the framework of the classic Norrish-Yang reaction, i.e. homolytic hydrogen transfer is the basis of the reaction. In the second part the cyclization reactions based on photoinduced electron transfer (PET) will be discussed and in the third part the spin-center-shift approach is elucidated. 

The Norrish-Yang reaction, with the spin-center-shift extension, facilitates access to a variety of cyclic compounds. This will be discussed here, with examples of the synthesis of three- to six-membered rings synthesis of macro- and bicydic compounds and the photochemistry of imides will not be covered. The examples especially demonstrate the capabilities of the reaction with regard to stereoselectivity. 

The Norrish-Yang reaction [63] is a widely used photochemical reaction, which consists of an intramolecular hydrogen abstraction by a photoexcited ketone, followed by carbon-carbon bond formation in the (l,n)-biradical intermediates (Scheme 9.38). 

One remarkable process is the photochemical synthesis of 3,4-dihydro-2H-l,3-oxazin-4-ones from a-sulfonyloxy-(3-keto amides (obtained by coupling of P-keto-carboxylic acids with amines, followed by treatment with an iodanyl mesylate). This allows the regioselective oxidation of less-activated C—H bonds and a C—O bond formation which is unusual for a Norrish-Yang reaction [69]. The formation of a 1,6-0—C biradical has been postulated as an intermediate (Scheme 9.42). 

EE3.2. 2-keto esters. The Norrish-Yang reaction of 2-keto esters has been the subject of only a limited number of studies [19,20, 2Id,22]. Encinas and his coworkers investigated the photochemistry of some alkyl esters of benzoylformic acid [23a]. These aromatic 2-keto esters have a n,n absorption maxima >330 nm. Similar to aromatic monocarbonyl compounds all observed products originate from an excited triplet state. 

Alicyclic Imides. In contrast to their aliphatic ketone counterparts, A-alkyl alicyclic imides (succinimides and glutarimides derivatives) could obtain a certain importance in the Norrish-Yang reaction. With a n,n absorption band between 230 and 270 nm, the 254 nm emission of a low-pressure mercury lamp is convenient for exciting... 

In the following section, the effect of different functional groups on the Norrish-Yang reaction will be discussed. 

J. Ring Substituents. One has to bear in mind that two main effects of ring substituents on the Norrish-Yang reaction of aromatic ketones exist. 

Second of all, on certain conditions an appropriate ort/zo-substituent in electronically excited aryl ketones (-R, -OR, -NR2 with R = alkyl) can serve as alternative hydrogen donor, i.e., an hydrogen atom may be abstracted from this ort/zo-substituent rather than from the side chain. In this way, carbo- and heterocycles with an annulated aromatic ring are accessible via Norrish-Yang reaction. (For synthetic applications see Secs. 3.4.2 and 3.4.3.)... 

Taking into account the wide-spread occurrence of molecules containing the tetrahydrofuran substructure, it is astonishing that there are only few examples of synthesis of these heterocycles by means of the Norrish-Yang reaction [38]. Interestingly, both aliphatic and aromatic ketones were used as exemplified by the photocyclization of ketones 17 [38b], 19 [38c], and 21 [3a] (Sch. 9). 

From a synthetic point of view, the extension of the concept, described in Sec. 3.4.2.1 (type Ih), on y-ketoamides, does not only provide an attractive method but also a molecular system that is very valuable for the improvement of the mechanistic understanding of the Norrish-Yang reaction. Thus, on irradiation y-ketoamides 50 cyclize to 5-lactams 51 in good yields [48]. It should be noted that the reaction outcome strongly depends on the solvent used. Whereas the irradiation in dichloromethane gives the 5-lactams 51, the only products formed in diethylether were pinacols [49]. The formation of cyclopropanes from 50 [50] described earlier is probably based on a misinterpretation of the spectral data [49]. 

The idea of a spin center shift as an extension of the synthetic scope of the Norrish-Yang reaction was already discussed twice in this chapter. A third example applies to the preparation of six-membered rings. Thus, by treating (3-ketoamides 42 (Sec. 3.4.2.1, Ih) with hypervalent iodine(III) reagents the oc-methanesulfonyloxy-(3-ketoamides 59 are obtained in excellent yields. On irradiation, the 1,5-biradicals 60 are formed, which are converted into the biradicals 61 by elimination of methanesulfonic acid. 

One of the first examples of a transannular hydrogen abstraction is Padwa s bicyclo[l.l.l]pentane synthesis published in 1967 [56]. By virtue of the considerable ring strain of bicyclo[l.l.l]pentanes the formation of 64 from 63 impressively demonstrates the synthetic scope of the Norrish-Yang reaction (Sch. 23). 

Two other examples of the synthesis of bicyclic compounds whose skeleton consists only of carbon atoms are shown in Sch. 24, each of them is instructive in its own way. Upon irradiation of the cyclohexane derivative 65, not the expected product from a hydrogen abstraction from the allylic position, but the bicyclo[3.3.1]heptane 67 was obtained by cyclization of the less stable biradical 66-B [57]. The reason for this is the exclusive hydrogen back-transfer of the more stable biradical and it underlines the importance of this process in regioselectivity phenomena of the Norrish-Yang reaction. 

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