Oxetane formation

Both oxetanes and p-hydroxy esters are formed following irradiation of aromatic carbonyl compounds in the presence of silyl ketene acetals. The products arise either by SET processes or by direct Paterno-Biichi additions. Griesbeck and Bondock have reported the influence of substrate concentration on the dia-stereoselectivity of the photochemical addition of aldehydes to (Z)- and ( )-cyclooctene. Miranda and co-workers have published physical evidence for the quenching of the triplet state of 2,4,6-triphenylpyrylium salts by 2,3-diaryloxetanes. 

Intramolecular oxetane formation has been examined in the sclareolide system. Typical examples are the photocyclizations of the substituted keto derivatives (32) and (33). The yields obtained are high in this series.  

The sensitizer dependency for the cycloreversion of tra/7, raf7 -2,3-diphenyl-4-methyloxetane has been studied. When chloranil is used as the sensitizer, the reaction proceeds via the radical cation of tr 3f7 -(3-methylstyrene, while with pyrylium salts the trans- iiXhQxvQ radical cation is involved.Other work in this area has examined the cycloreversion of the oxetanes (34) using (35) or chloranil as the sensitizers.  

Doubt has been cast on the stereochemical assignments within oxetanes obtained from the addition of benzaldehyde to alkenes. The authors of a recent report were unconvinced by earlier assignments of stereochemistry to the adducts (44) and (45) formed from the addition of benzaldehyde to styrene. The previous study has been repeated and a 3 1 ratio of the trawj.cw-oxetanes has been reported. Re-investigation of the effect of methyl substituents was also carried 

Further work has been carried out to study the facial diastereoselectivity of the addition of benzaldehyde to alkenes. ° In this study the three enamines (49)-(51) were used as the substrates to which benzaldehyde was added photochemically. The results show that addition does occur to all three enamines but with varying degrees of success as far as diastereoselectivity is concerned. Thus addition to (49) gives the two oxetanes (52) and (53) but with only 32% de. Poorer selectivity is observed with (50) when (54) and (55) are obtained. The best de of 62% is achieved from (51) where the products are (56) and (57). The photochemical addition of the aldehydoester (58) to the enamine (59) results in the formation of the oxetane (60). This product is obtained in around 30% yield and it can be transformed into racemic oxetin (61). Bach has reviewed the stereocontrol that can be exercised on the formation of oxetanes. The regioselectivity of the addition of triplet carbonyl compounds to alkenes has been interpreted for the first time in terms of hard and soft acid-base systems. The authors of this report suggest that there is overall good agreement between HSAB prediction and experimental fact. 

Bach d has reviewed photochemical (2 + 2)-cycloaddition reactions including oxetane-forming processes and the stereochemical aspects of the reactions are highlighted. Earlier studies by the same author reported the results of irradiation of the alkene (88) in benzene with benzaldehyde to give the oxetane (89). These 3-oxetanols have been subjected to further study and have been 

The results of irradiation ( i 290 nm) of a series of aldehydes and ketones (91) in the presence of the silyl acetals (92) have been reported. The reactions are both solvent and silyl group dependent and the best results are obtained when the solvents used are /z-hexane, THF, diethyl ether or benzene and with the silyl group TBDMS. The products are the oxetanes (93) and the silyl-migrated product (94) in a ratio greater than 95 5 respectively. There is no evidence for the formation of the isomeric oxetane. Other studies from this research group have examined the photochemical addition of a series of aryl aldehydes (95) to the cyclic silyl alkenes (96) brought about by irradiation at X, 290 nm in methylene chloride solution. The additions encountered take place with regio and exo selectivity as shown by the yields and ratios of the products (97). 

The photoaddition of aldehydes or ketones to furan has been reported over the years. Griesbeck and his co-workers have established that the diaster-eoselectivity of the addition of benzaldehyde to furan is 212 1 for the formation of the exo and endo products (98) and (99). The study was extended to the addition of other carbonyl compounds (100) and the ratio of products from these additions is shown under the appropriate structure (101) and (102). L-Ascorbic acid and some of its derivatives (103) also undergo photochemical addition of aromatic aldehydes and ketones. With benzaldehyde and benzophenone the products obtained are the mixture of (104) and (105) with a preference for the formation of the former. The stereochemistry of the addition of the excited state carbonyl compound to ascorbic acid favours the path where the phenyl and the alkoxy groups are cis on the resultant oxetane. Benzaldehyde adds photochemically to the enamine (106) when the mixture is irradiated in acetonitrile solution. Three products are 

Photocycloaddition of benzaldehyde or benzophenone to the alkene (110) follows the usual path and affords the oxetanes (111) in moderate to good yields. With the simple cyclopropyl substituted alkenes the biradical intermediate in the addition does not undergo cyclopropane ring opening, but with an appropriately substituted cyclopropane ring opening does occur. Thus irradiation of benzophenone with the alkene (112) yields the bis-adduct (113) where a second addition of benzophenone to the ethene bond in (114), the primary product, has occurred. Addition of aldehydes to (112) is not complicated by this second addition and the primary products obtained were identified as the tetrahydrooxepins (114). 

The primary photochemical product formed from the irradiation of the 2-thiones (115) in the presence of alkenes is the oxetanes (116). The reaction conditions use Pyrex filtered light in benzene solution. Under these conditions the initial product is unstable and reacts further either by C-O or C-S bond fission which leads to the isolated products (117) and (118) in the yields shown. 

The addition of benzophenone, for example, affords low yields of the four isomeric oxetanes (66, R = Ph), (67, R = Ph), (68) and (69). These addition reactions take place in competition with the conversion of the alkene into (70) and (71). The conversion to these alkenes presumably is the result of energy transfer from the excited ketone. The addition of methyl phenylglyoxalate to the alkene (65) affords a single adduct (72) in 70% yield while the addition of benzil to the same alkene yields the two adducts (66, R = PhCO, 31%) and (67, R = PhCO, 6%)  

Chung and Ho have reported the details of the photochemical addition of electron-deficient alkenes to the substituted adamantanones (73). All of the ketones undergo reaction from the singlet state and, for example, the addition to acrylonitrile affords the two adducts (74) and (75) in an anti syn ratio of 60 40 which is the approximate value for the products of all systems studied. The irradiation at 300 nm of the alkene (76) in neat spectral-grade acetone affords (77), referred to as a photo-Conia product, in 52% yield. A trace of the oxetane (78) was also found. In hexadeuterioacetone the ratio of the products was found to be 2 1 

Irradiation of the enone (80) at 282 nm brings about the formation of the oxetane (81), and this process has been used as a key step in the development of a synthesis of 2,7,9-trimethylenetricyclo[4.3.0.0 ]non-4-ene. Such intramolecular additions are popular methods for the formation of polycyclic compounds that can be used as starting materials in syntheses. An efficient example of this from earlier years is the formation of the oxetane (82,90%) from the intramolecular cyclization of the enone (83). The oxetane formed is a key intermediate in a new efficient route to enrfo-hirsutene. ° A review of the application of the Diels-Alder/Patemo-Buchi reaction as an approach to di- and tri-quinanes has been published.  

The addition of benzophenone, for example, affords low yields of the four isomeric oxetanes (66, = Ph), (67, R = Ph), (68) and (69). These addition reactions take 

The addition of aldehydes and ketones to alkenes is a convenient high yield reaction for the synthesis of oxetanes. The regiochemistry shown by the addition process can usually be predicted on the basis of the better biradical formed by the addition of the oxygen of the excited carbonyl group to the alkene moiety. Such is the case with the photoaddition of 

Addition can also take place to other unsaturated compounds such 

Furan is a well-used substrate for oxetane formation. Typically 

The silyl diene (90) photochemically adds benzophenone via a SET mechanism to yield the two oxetanes (91, 18X) and (92, SIX) on irradiation at 436 nm in acetonitrile solution. The oxetanes are accompanied by the (242)-dimer of the diene. The reaction appears to be efficient and can be carried out with a variety of diaryl ketones. 

A patent has been lodged dealing with the photochemical synthesis of the thiolactones (82) from the thioacids (83). The cycloadduct (84) is the sole product from the irradiation of 1,1-diethoxyethene with biacetyl in non-polar solvents. The authors suggest that an electron transfer process is operative and that the cycloaddition therefore proceeds via the zwitterion (85). A study of chiral induction in the photochemical synthesis of oxetanes using the chiral 

The lactone (90) undergoes photoaddition of benzophenone when the reactants are irradiated in thiophene solution.Two isomeric oxetanes, (91) and (92), are obtained from this process, the latter of which thermally rearranges to yield (93). 

One of the key steps used in a new synthesis of the bis(tetrahydrofuran) moiety of Asteltoxin (94) is the photoaddition of the propanal (95) to 3,4-dimethylfuran, yielding the adduct (96). This cycloaddition is a common outcome of the irradiation of aldehydes or ketones with furans. An analogous adduct (97) results from the photoreaction of butyl glyoxalate with 2-methylfuran. Two other products [(98) and (99)] are also formed, the first of which is presumably the result of ring opening of the isomeric oxetane (100), while (99) is produced by a hydrogen abstraction radical coupling pathway. 

Schreiber et have described a route to threo aldols using the acid-catalysed ring opening of aldehyde-furan photoadducts (101). 

Benzophenone photoreacts with 2-methylselenophene to yield the adduct (102). The photoaddition of benzophenone to the tricyclooctanones (103) has been reported to yield oxetanes.  

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With aromatic carbonyls, oxetane formation appears to arise from the carbonyl triplet state, as evidenced by quenching studies. For example, benzaldehyde irradiated in the presence of cyclohexene yields products indicative of hydrogen abstraction reactions and an oxetane ... 

The reaction of carbonyl compounds to olefins often yields products difficult to obtain synthetically by other routes. The excellent yields obtainable under proper conditions make this reaction of definite preparative interest. Examples of some synthetic applications of oxetane formation follow ... 

For oxetane formation from formaldehyde and ethylene, we should consider the following four transition states and intermediates for the reaction<181) ... 

Yang has observed that cis-trans isomerization of 3-methyl-2-pentenes is accompanied by oxetane formation and concluded that intermediates such as (22) are common to both isomerization and oxetane formation/825 Deuterium isotope effects are also consistent with the involvement of this type of intermediate/83,845 ... 

The other photochemical reactions of simple carbonyls mentioned earlier in this chapter—type I cleavage (a-cleavage) and oxetane formation—will be discussed in Chapter 4. 

The Photochemistry of Simple Carbonyl Compounds Type I Cleavage and Oxetane Formation... 

In Chapter 3 we discussed two photochemical reactions characteristic of simple carbonyl compounds, namely type II cleavage and photoreduction. We saw that photoreduction appears to arise only from carbonyl triplet states, whereas type II cleavage often arises from both the excited singlet and triplet states. Each process was found to occur from discrete biradical intermediates. In this chapter we will discuss two other reactions observed in the photochemistry of carbonyls, type I cleavage and oxetane formation. 

Table 4.10. Reactivity of Various Aromatic Carbonyls toward Oxetane Formation and Photoreduction Compared to the Nature of the Lowest TripletiB3,9 Bm...

In a recent study of intramolecular oxetane formation in naphthoylnor-bornenes Sauers and Rousseau provided evidence that two distinct excited states are involved<99) ... 

Lange and Bosch<109) reported the interesting intramolecular oxetane formation shown below. Reduction with lithium aluminum hydride afforded m is-9-decalol (32%) ... 

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