Photochemical four-membered ring synthesis

Synthesis of the propellane (4) requires FGA. With two four-membered rings probably to be made by photochemical reactions, a carbonyl group on the six-membered ring is best, allowing a 2 + 2 disconnection. 

Photochemical reactions provide a classical access to four-membered ring compounds that generate major interest in organic synthesis, notably as intermediates in multistep syntheses. The [2 + 2] photocycloaddition of a,(3-unsaturated carbonyl and carboxyl compounds with alkenes and [2 + 2] photocydoaddition of ketones with alkenes (the Paterno-Buchi reaction) are discussed in Chapters 6 and 7, respectively. Yet, aside from these transformations, a variety of further reactions provides a systematic access to four-membered rings that possess a wide structural variation. Four-membered ring compounds may also be created via less-systematic photochemical transformations, many of which can be carried out without additional chemical activation. As a consequence, such transformations are rendered not only very convenient but also extremely interesting within the context of green chemistry. ... 

Grandisol has previously been synthesized using a number of photochemical procedures. Two recent reports demonstrate the utility of the copper catalyzed photocycloaddition (see Sch. 28) in the synthesis of the four member ring observed in the boll weevil pheromone. The first example [41] is a chiral synthesis and the second pathway [42] provides the racemic product. 

This subject has recently been reviewed6 and we shall concentrate on the different approaches to grandisol outlined in that review. Many of these approaches can clearly be used for the other compounds. An early approach was a chiral pool strategy from the simpler and commercially available terpene (R)-( (-linalool 38. Though this did not lead to a useful synthesis, it pointed the way to effective methods, particularly the Cu(I)-catalysed photochemical closure of the four-membered ring. 

In our analysis of the synthesis of rings of various sizes, we concluded (Chapter 29) that four-membered rings are uniquely difficult. For this reason, a special method, the photochemical 2 + 2 cycloaddition is often used to make four-membered rings. Some 2 + 2 thermal cydoadditions, particularly of ketenes (Chapter 33), and some ionic reactions (page 272) are also useful. 

Cyclopentenone (3) has been used in photochemical syntheses of four-membered rings. Disconnection gives keto aldehyde (4) and the branch point disconnection (a) gives aldehyde (5) and synthon (6) for which we might consider a-bromacetone (Chapter 25), allylic bromide (7) (Chapter 26), or propargyl bromide (8) (Chapter 26), using in each case the enamine of aldehyde (5) to ensure control. One successful synthesis is given. 

A new synthesis of d/-isocaryophyllene has been used for the photochemical addition of 2-methylpropene to cis,cis-2,6-cyclononadienone as a method of generating the four-membered ring. ... 

Four-membered Ring Nitrogen Heterocycles.— The synthesis of azetidine and its derivatives by akylation of an external or an internal amine is well known, and two more examples were reported in 1980. Interest in simple alkyl substituted azetidines now lies in studies on their stereo-preferences, and conversions to other important systems. That said, two photochemical investigations surprisingly turned up such systems as unexpected major products. Pete et while extending their work on 2-amino-cyclohex-2-enones examined the consequence of N-sulphonylation on their photochemical behaviour, and instead of getting aziridines as the principal products, they obtained azetidines (Scheme 35). These reactions were not as clean as the earlier ones, and aryl migration... 

Photolysis is an important method for the synthesis of fused four-membered N-containing rings. Photochemical rearrangement of 363 in acetonitrile afforded the fused azetidine 364 in a reasonable yield (Equation 44). The substituents on the rings did not seem to have influenced the photorearrangement <2003BML1561>. 

Though the rearrangement step transforms a stable tertiary cation into a less stable secondary cation, relief of strain in expansion from a four- to a five-membered ring makes the alkyl migration favourable. In 1964, E.J. Corey published a synthesis of the natural product a-caryophyllene alcohol that made use of a similar ring expansion. Notice the photochemical [2+2] cycloaddition (Chapter 35) in the synthesis of the starting material. 

In summary, intramolecular reactions of a considerable variety of diones provide interesting mechanistic questions as well as a route forj construction of four- and five-membered rings in high photochemical and chemical yields. Except for a synthesis of cis- and trans-bicyclo[7.1.0]decan-2-one from cyclodecane-1,2-dione 122), this potential has been ignored. 

The replacement of carbon atoms of cyclobutane by heteroatoms introduces functionalities which show increased reactivity resulting from Ae ring strain. This often leads to unusual properties which make four-membered heterocycles useful as synthetic intermediates.However, it also adds a new dimension of difficulty concerning the synthesis of these heterocycles. A valuable source of four-membered heterocycles uses the combination of ir-bonds. This section is devoted to a survey of these reactions with special focus on selectivity in all of its forms. Photochemical cycloadditions are not discussed here since they are covered elsewhere. In several instances, reactions will be described which can formally be considered as combinations of ir-systems but probably take alternate pathways. However, since the real mechanisms are often unknown, these very useful reactions will be discussed here. 

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