Marshalls synthesis of

The above example is a clear black or white situation. Unless the dimethyl substituent is removed, the transform just cannot proceed. The grey areas cause just as much of a dilemma for the chemist, In Marshall s synthesis of isonootkatone two possible stereoisomers could have resulted. 

ACS Symposium Series American Chemical Society Washington, DC, 1977. 

As we have been adding to the data base at Du Pont (to the one and two group tables), the question has often been raised how much detail should we go into in the qualifiers This is somewhat of a dilemma, many of the industrial reactions we are dealing with have only been considered for a limited number of substrates. It is not clear whether qualifiers should be incorporated that restrict the transforms to only those cases where it is known to work or whether only those which are known to fail should be specifically excluded. Both ways take an immense amount of literature work to do consistently. 

We all know that butadiene can be dimerized under catalytic conditions to a wealth of different products. Addition of alkyl substituents changes the product mix and introduces a variety of different stereoisomers as well. What happens if we put functional groups on butadiene. Do all the reactions still proceed - do you get any new ones, etc. We do not know and serious doubt whether many experiments have ever been run 

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In a variation of these reactions, Grieco and Masaki used p-toluenesulfonyl groups to direct alkylation reactions in the formation of carbon chains and then cleaved the sulphones with lithium in ethylamine. This type of synthetic construction involving the use of sulphur-containing molecules has become a typical sequence in organic syntheses. In this case, the reactions formed part of successful syntheses of squalene and sesquifenchene and were carried out without any migration or loss of stereochemical integrity of the double bonds. Similar sequences have been reported by Trost (prenylation reactions) and Marshall (synthesis of a cembranoid precursor). 

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