Sigmatropic shift antarafacial

To be very enantioselective, this reaction has to meet several important requirements. First, photoenols have to be produced as either pure Z or E stereoisomers to allow enantioselective photodeconjugation. Even so, protonation of the Z or stereoisomers from the same, rear side, for example, would produce opposite enantiomers and a low enantiomeric excess (ee) would result (Scheme 3). Fortunately, photoenolization of aliphatic enones is only possible from the Z isomer excited in its singlet state, and the excited molecule has to adopt an s-cis conformation to place the excited carbonyl and the y-H close enough to allow y-H abstraction. Consequently, the enol is formed in a unique configuration. All these observations have led several groups to propose a concerted process involving a 1,5 antarafacial sigmatropic shift for the formation of photodienols [16]. 

Figure 4.9. Structural and orbital representations of a 1,3 antarafacial sigmatropic shift.

The direct connection of rings A and D at C l cannot be achieved by enamine or sul> fide couplings. This reaction has been carried out in almost quantitative yield by electrocyclic reactions of A/D Secocorrinoid metal complexes and constitutes a magnificent application of the Woodward-Hoffmann rules. First an antarafacial hydrogen shift from C-19 to C-1 is induced by light (sigmatropic 18-electron rearrangement), and second, a conrotatory thermally allowed cyclization of the mesoionic 16 rc-electron intermediate occurs. Only the A -trans-isomer is formed (A. Eschenmoser, 1974 A. Pfaltz, 1977). 

A similar analysis of the 1,5-sigmatropic shift of hydrogen leads to the opposite conclusion. The relevant frontier orbitals in this case are the hydrogen Is orbital and ij/j of the pentadienyl radical. The suprafacial mode is allowed whereas the antarafacial mode is forbidden. The suprafacial shift corresponds to a favorable six-membered ring. 

This view also explains satisfactorily why a [1, 3] sigmatropic shift of a hydrogen in 1, 3 pentadiene will not be possible. In this case, a [1, 3] shift would have to be antarafacial and such a rearrangement would be structurally prohibited. 

The outcome of all this for photochemical sigmatropic shifts is that those most commonly observed are of order (1.3) or (1.7) these involve 4 or 8 electrons, respectively, and occur in a suprafacial manner. Examples of photochemical 1.3-shifts of hydrogen are found for monoalkenes (2.25) and for conjugated dienes 2.26). In the case of dienes a 1,3-shift is favoured over a 1,5-shift, because for the latter to occur photochemically it would have to take place in an antarafacial manner. Note that in both examples the direction of... 

According to the Woodward-Hoffmann rales, five concerted transition states are possible for the Claisen as well as the closely related Cope rearrangements chair, boat, twist, cross and plane (Table 6). Only the chair and boat TS have to be considered, as twist, cross and plane are antarafacial-anta-rafacial processes and require highly elevated temperatures. - For the correct prediction of product stereochemistry it is nevertheless crucial to know the preference for chair- or boat-like transition state in the actual 3,3-sigmatropic shift. 

The [1,5] shift would be a suprafacial reaction. The [1,7] shift must be antarafacial in the v component to be thermally allowed. The proton, located at carbon A in 6-20, moves from the bottom side of the six-mem-bered ring to the top side of the w system at the other end. In general, the antarafacial process, necessary for a thermal [1,7] sigmatropic shift, occurs with ease, especially when compared to the antarafacial process that would be required for a thermal [1,3] sigmatropic shift. 

Sigmatropic shifts represent another important class of pericyclic reactions to which the Woodward-Hoffmann rules apply. The selection rules for these reactions are best discussed by means of the Dewar-Evans-Zimmerman rules. It is then easy to see that a suprafacial [1,3]-hydrogen shift is forbidden in the ground state but allowed in the excited state, since the transition state is isoelectronic with an antiaromatic 4N-HQckel system (with n = 1), in which the signs of the 4N AOs can be chosen such that all overlaps are positive. The antarafacial reaction, on the other hand, is thermally allowed, inasmuch as the transition state may be considered as a Mobius system with just one change in phase. 

Vitamin D is associated with biological functions, such as bone formation, immune system responses, cell defences and anti-tumour activity.615,616 Vitamin D comes in two closely related forms, vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol), and their metabolites. Both vitamin D2 and D3 occur naturally in some foods. However, vitamin D3 (63) can also be synthesized in skin cells called keratinocytes from 7-dehydrocholesterol (provitamin D 64), which undergoes a photochemical six-electron conrotatory electrocyclic ring opening at 280nm to previtamin D3 (41 see also Scheme 6.8), which spontaneously isomerizes to 63 in a thermal antarafacial hydride [l,7]-sigmatropic shift (Scheme 6.21). Both vitamin D2 and D3 are subsequently converted to active hormone 1,25-D by enzymes in several steps. The recommended daily intake of vitamin D for humans is 5 10 pg per day. For example, 15 ml of fish liver oils and 100 g of cooked salmon contain approximately 35 and 10 pg... 

Vitamin D3 is naturally synthesized in human skin by a spontaneous thermal antarafacial hydrogen [l,7]-sigmatropic shift in previtamin D3, which is produced from 64 upon solar UVB irradiation in the first step.621... 

If these reactions occur in uncatalyzed processes where bond breaking and bond formation are taking place concertedly, and not in two-step pathways via ionic or diradical intermediates, then the stereochemistry of these sigmatropic shifts can be predicted in a qualitative manner 1 -4. According to the Woodward-Hoffmann rules the thermally allowed reaction should take place in an antarafacial fashion across the allylic framework. The shifting hydrogen has to move from one side of the allylic plane to the other as depicted below. 

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