Q7(a). Paternò–Büchi reaction; NMR of bromopropanes; IR of α-chloro ketones

Introduction. (i) is a [2+2] photocycloaddition of a ketone to an electron-rich alkene; (ii) counts chemically different proton sets and applies the n+1 rule; (iii) is a field effect of an α-halogen on ν_C=O.

(i) Paternò–Büchi reaction

Scheme: Excited acetone, 1,4-biradical, oxetane.

1. Acetone absorbs (n→π*); the excited state (S1, and T1 after intersystem crossing) has an electron-poor, radical-like oxygen.
2. The oxygen adds to the alkene to give the more stable 1,4-biradical: O bonds to the terminal CH₂, leaving the radical on the carbon bearing OR (stabilised by the oxygen lone pair) and on CMe₂.
3. Spin inversion and ring closure give an oxetane: major 3-alkoxy-2,2-dimethyloxetane; the other orientation gives some 4-alkoxy-2,2-dimethyloxetane (alkoxy group next to the ring O).

(ii) 1H NMR of the bromopropanes

(iii) Axial and equatorial α-chloro ketone

1. In (II) the C–Cl bond is equatorial, almost in the plane of the C=O and close to it in direction. The C–Cl and C=O dipoles (and the lone pairs of Cl and O) repel (field effect); the polar form C+-O⁻ is disfavoured, the C=O keeps more double-bond character and ν_C=O rises.
2. In (I) the C–Cl bond is axial, nearly perpendicular to the C=O; there is little interaction, and ν_C=O stays close to that of the parent ketone.
3. So (II) absorbs at higher wavenumber. The rule (equatorial α-halogen raises ν_C=O, axial does not) is used to assign the orientation of halogens in steroid ketones.

Conclusion. (i) Triplet acetone + vinyl ether → 1,4-biradical → 3-alkoxy-2,2-dimethyloxetane (major). (ii) 1-Bromopropane: 3 signals (t, sextet, t); 2-bromopropane: 2 signals (d, septet). (iii) (II), the equatorial chloro ketone, absorbs at higher ν_C=O.

Application. The Paternò–Büchi reaction is the most direct route to oxetanes, the four-membered ether ring present in paclitaxel and used as a polar group in drug design; the α-halo ketone IR rule fixed the configurations of many halogenated steroids.