Cyclobutanol fragmentations

In 1980, Baldwin developed a modification of the de Mayo reaction using dioxinone heterocycles as covalently locked enol tautomers of P-keto esters. Thus intermolecular cycloaddition of 2,2,6-trimethyl-1,3-dioxolenone 133 occurs in good yield using stoichiometric quantities of a variety of alkenes. For example, irradiation of 133 with tetramethylethylene yields the cyclobutane adduct 135 in 90% yield. This adduct is converted to cyclohexenone 138 in two steps. Controlled reduction of 135 with diisobutylaluminum hydride (DIBAL) gives keto aldehyde 137 (after spontaneous loss of acetone from hemiacetal 136 and retro-dXdo cyclobutanol fragmentation), which on exposure to acidic conditions affords cyclohexenone 138 in 76% yield. 

Cyclobutanol formation is not usually an efficient process for simple aliphatic ketones. It has, however, been shown12 that irradiation of the urea inclusion complex of 5-nonanone is more effective, providing l-butyl-2-methylcyclobutanol in 40% yield, with the balance of the ketone undergoing photochemical fragmentation. The cyclobutanol product is a 97 3 cisjtrans mixture. In the absence of urea, photolysis proceeds to give the cyclobutanol in 24% yield, as a 60 40 cisjtrans mixture. Photocyclization has also been improved by inclusion in zeolites13. 

The influence of these various effects may be manifested in measurable parameters of the reaction like the overall quantum yields (On) and the photoproduct ratios for fragmentation to cyclization (E/C) and for trans to cis cyclobutanol formation (t/c) as shown in Scheme 41. The values of these quantities and their variations as the media are changed can provide comparative information concerning the relative importance of solvent anisotropy on Norrish II reactions, also. Specifically, they reveal characteristics of the activity of the walls and the size, shape, and rigidity of the reaction cavities occupied by electronically excited ketones and their BR intermediates. 

As shown in Figure 42 for the Norrish II reactions of a simple ketone, 2-nonanone, not only do the shapes of the products differ from those of the reactant, but so do their molecular volumes [265]. Interestingly, the volume of the fragmentation products, 1-hexene and 2-hydroxypropene (which ketonizes to acetone), are closer in volume to 2-nonanone than is either of the cyclization products. They are also capable of occupying more efficiently the shape allocated by a stiff solvent matrix to a molecule of 2-nonanone in its extended conformation the cross-sectional diameter of either of the cyclobutanols is much larger than that of extended 2-nonanone or the fragmentation products when spaced end-on. Both of these considerations should favor fragmentation processes if isomorphous substitution for the precursor ketone in the reaction cavity is an important requirement for efficient conversion to photoproducts. 

These expectations have been borne out by experiment [293], For instance, 2-tridecanone gives rise to E/C ratios in Na-X (1.0) and Na-Y (0.9) zeolites which are very similar to those found from valerophenone in the same media. However, whereas only fragmentation products were detected from valerophenone irradiated in ZSM-5 and ZSM-11, the E/C ratios in these zeolites with narrower channels were 4.3-4.5 from 2-tridecanone. Clearly, the channel cross sections of these zeolites (>28A2) can accommodate the c-BR conformations necessary to form cyclobutanols. 

The restricted motion of molecules and of fragments such as free radicals formed by photodissociation results in interesting differences in the photochemistry of some molecules in solution or as guests in inclusion compounds. To take one example, the aliphatic ketone 5-nonanone can yield fragmentation or cyclization products via the biradical formed through intramolecular hydrogen atom abstraction (Figure 8.18). In the photolysis of the inclusion compound the cyclization is the preferred reaction, and there is a marked selectivity in favour of the ay-isomer of the cyclobutanol. 

The ratio of Type II fragmentation to Type II cyclization products may depend strongly on the excited state from which reaction occurs. The lowest-energy pathway for fragmentation requires continual orbital overlap between developing p bonds. Cyclobutanol formation, however, has less stringent orbital orientation requirements. When the configuration of the ketone is unfavorable... 

Posner et al. found that commercial aluminium oxide is able to promote the oxidation of alcohols employing chloral as hydride acceptor.30 The reaction operates at room temperature in inert solvents like CCI4 and surprisingly no base-induced condensations are reported. Basically, the same experimental conditions were later applied for the oxidation of cyclobutanol,31 a compound with a great propensity to fragmentation under the action of other oxidants. 

A laser flash study of the photoreactions of hexan-2-one and 5-methylhexan-2-one has provided evidence for the existence of the triplet 1,4-biradicals produced by the y-hydrogen abstraction typical of Norrish Type II reactivity. The photochemical behaviour of the alkanone, nonan-5-one, in urea inclusion compounds has been studied. In solution, irradiation of nonan-5-one yields hexan-2-one, propylene, and two cyclobutanols. In the clathrate, the fragmentation products were essentially the same but only one cyclobutanol was observed. The cyclization fragmentation ratio was established as 0.67, compared with 0.32 in methanol. The authors suggest that the CIS-cyclobutanol has less stringent rotational requirements and that it is this isomer (43) which is formed in the clathrate. 

The behaviour of irradiated butyrophenone in the presence of triphenyl-phosphine has been studied.Direct irradiation of the acetophenone derivatives (44) using a pulsed nitrogen laser (337 nm output) as the energy source yields the cyclobutanols (45) as the principal products. The minor product in each case was the corresponding acetophenone, and the formation of the cyclobutanols as the main product was solvent-independent. When crystalline samples were irradiated, less cyclobutanol was formed in all cases. An X-ray study was also carried out in conjunction with the above this showed that the P-hydrogen (relative to the carbonyl) was accessible for H-abstraction in the crystal, but no confirmatory evidence for this was obtained from the photochemistry. The change of product ratio from solution to solid phase is attributed to restricted cyclization within the crystal rather than an enhancement of the fragmentation path. 

An intriguing combination of two cyclopropyl systems allows cyclobutanone formation according to equation 105 base-induced fragmentation of an intermediate cyclobutanol stereoselectively forms a functionalized olefin . 

The Type II photoreactions of 2a-propyl-3-oxo-5a-steroids (317) give cyclobutanols (318) in higher proportion, relative to the alternative fragmentation products (319), than would be expected by analogy with comparable reactions of... 

Enantiomerically pure (+ )-64, available from the racemate by recrystallization of the diastereomeric bisulfite complexes with (-)-a-phenylethylamine, was converted to the (Z)-enol tosylate 65 (49%). This material was separated from the corresponding ( )-olefin (3%) and starting material 64 (19%) by chromatography. Condensation of 65 with optically active cw-2-ethylcyclopropyl lithium (66) afforded a single cyclobutanol 67 in 76% yield. Fragmentation to the desired rranj-disubstituted cyclopropane ring was induced by addition of tetrabutylammonium fluoride, which also served to equilibrate the initially formed cis compound to a mixture of 68b to 68a (9 1) in a combined yield of 86%. The less stable 68a could readily be equilibrated to the mixture (9 1) of 68a,b by treatment with carbonate in methanol. 

Norrish Type II reactivity is often a common reaction path for ketones with available Y 7< °sens. Hydrogen abstraction by the excited carbonyl group results in the formation of a 1,4-biradical which can undergo either bond cleavage to reform the carbonyl group and an alkene or bond formation to yield a cyclobutanol derivative. The fragmentation path is followed by the ketone (13). The interest in this reaction is the control which can be exercised on the ketonization of the resultant enol (14). Apparently in the presence of (->-ephedrine asymmetric formation of the final product, (R)-2-methylindanone (15),... 

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