Cyclobutanol formation

Conversion of pregnanes to androstanes via the Schmidt Rearrangement 17/3-aminoandrost-5-en-3/3-ol, 145 Cyclobutanol formation by ketone irradiations... 

Photochemical C —H insertion of ketone 1 proceeds by initial photoexcitation to give an excited state that can be usefully considered as a 1,2-diradical. Intramolecular hydrogen atom abstraction then proceeds to give a 1,4- or 1,5-diradical, which can collapse to form the new bond. This approach has been used to construct both four- and ftve-membered rings12 11. Photochemical-ly mediated cyclobutanol formation is known as the Norrish Type II reaction. 

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. 

Diketones cyclize much more efficiently than simple ketones. Photochemical cyclobutanol formation is the key step in a novel route14 to 1,3-cyclopentanediones, as exemplified by the conversion of l-bromo-5-phenyl-2,3-pentanedione to 4-phenyl-l,3-cyclopentanedione. 

In a more constrained system 2, cyclobutanol formation can also be more efficient15. Note that in Ihis case, it is also highly diastereosclcctive. This photocyclization is a key step in the total synthesis of the sesquiterpene antibiotic (—)-punctatin. 

Aliphatic ketones (R = alkyl) usually undergo preferential a-cleavage on excitation nevertheless, cyclobutanol formation via intramolecular H-abstraction and cyclization is favoured (a) by an a-fluoro substituent, (b) by the rigidity of the group R (e.g. for R = cycloalkyl or bicycloalkyl), or by irradiation in either (c) inclusion complexes or (d) the crystal itself (solid state irradiation). 

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. 

The photochemistry of isomesityl oxide is rather interesting in that cyclobutanol formation and type I cleavage proceed with a fair quantum yield.361 The efficiency of the process may indicate that energy transfer to the double bond is not favored.361 However, it is likely that most of the photoreaction proceeds from an excited singlet. 

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... 

There are four distinct processes initiated by y-hydrogen abstraction in excited carbonyl compounds Norrish type II photoelimination, Yang photo-cyclization (cyclobutanol formation), Yang photoenolization (o-xylylenol formation), and (3-cleavage of radicals from carbons adjacent to the radical sites of the 1,4-biradicals. Some of these require unique structures and generate distinct products. 

There has been considerable interest in the factors that control the stereoselectivity of cyclobutanol formation. Three main factors were identified quite early pre-existing conformational preferences due to steric effects or to internal hydrogen bonding solvation of the OH group and variable rotational barriers for cyclization. More recently Griesbeck has proposed that orbital orientation favoring soc produces another form of conformational preference in triplet biradicals [55], These factors have different importance depending upon the molecule. 

Still another reaction which is readily susceptible to our n-7r model is the Norrish Type II with concomitant cyclobutanol formation (i.e. the Yang reaction 33)). This mechanism was described in detail by the author 1,3,12), again in those early papers. Here the two dimensional circle-dot-y notation suffices and is convenient. Note Equation 8. 

Photodecomposition. The photochemistry of 2-pentanone is distinguished by the possibility of "Y-hydrogen abstraction by the carbonyl oxygen (Norrish type II process). The biradical intermediate thus formed allows the possibility of cyclobutanol formation. 

The type III process is always very small in yield. Triplet quenchers almost completely quench cyclobutanol formation (13). 

The earliest report on the effect of micelles on Type II reactions dealt with the dependence of the ratio of disproportionation to cyclobutanol formation for the intramolecular hydrogen abstraction reaction of octanophenone (2<5 R=C4H9) and valerophenone (25 R = CH3) (Scheme XI)32). The reaction in homogeneous solu-... 

The photochemical formation of cyclobutanols is substantially favored if the ethylene that would be formed in a type II elimination must have a bridgehead double bond.120) Jn 1-adamcUitylacetone, 77, the strain is sufficient to substantially inhibit the elimination of acetone from the molecule ion. 12 ) Cyclobutanol formation is the virtually exclusive photochemical pathway for 71 and related bridgehead acetone derivative. 

Due to the very limited amount of experimental data available, a choice between the two mechanisms is even more difficult for reaction III than for reaction II. Orban et investigated the photochemical rearrangement, in pentane, of an aliphatic, optically active ketone with a single asymmetric carbon atom in the y position. Their results demonstrate a partial retention of configuration during photochemical cyclobutanol formation, which can be explained neither by a biradical mechanism alone, if this involves a long-lived radical, nor by a concerted mechanism alone. The results are reconcilable with the competitive participation of both mechanisms, but they are just as compatible with the assumption of the production of a short-lived biradical whose rates of racemization and of cyclization are comparable. 

U.v. irradiation of the unsaturated A-seco-5-ketone (324) gave none of the expected oxetan (325), but instead produced the cyclobutanols (327) as major products, along with a little of the B-seco decarbonylation product (328). Cyclobutanol formation proceeds through hydrogen transfer from C-2 to the carbonyl oxygen, which is followed by cyclization of the 2,5-biradical (326). Similar reactions occur with the alkynyl-ketone (329) and with the saturated analogue (330). ... 

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