Giese method

Scheme 9. Danishefsky s synthesis of bicyclo[3.3.0]octane 52 using Giese s reductive mercury method.

For a summary of methods of radical formation, see Giese, B. Radicals in Organic Synthesis Formation of Carbon-Carbon Bonds Pergamon Elmsford, NY, 1986, p. 267. For a review on formation of free radicals by thermal cleavage, see Brown, R.F.C. Pyrolytic Methods in Organic Chemistry Academic Press NY, 1980, p. 44. 

Curran2 has reviewed recent applications of the tin hydride method for initiation of radical chain reactions in organic synthesis (191 references). The review covers intermolecular additions of radicals to alkenes (Giese reaction) as well as intramolecular radical cyclizations, including use of vinyl radical cyclization. 

A concise collection of some modem methods of radical formation via rupture of C-E, C-G and C-A bonds, as well as from alkenes and cyclopropanes, by metals, organometallic hydrides, and photochemical and electrochemical means, are given in the last Chapter of Giese s book [28]. For some examples of radical generation and reactions leading to cyclic and polycyclic compounds see next Chapter (Heading 6.1.3). 

In the past few years, however, very efficient new methods of cyclisation proceeding via radical intermediates have been developed and several reviews [19a] and a comprehensive book by Giese [19b] have been published. Rather than reactions involving the dimerisation of two radicals -as in the Kolbe electrochemical synthesis [20] or the radical induced dehydrodimerisation developed by Viehe [21]-more important are the reactions between a radical with a non-radical species. The advantage of this type of reaction is that the radical character is not destroyed during the reaction and a chain-reaction may be induced by working with catalytic amounts of a radical initiator. However, in order to be successful two conditions must be met i) The selectivities of the radicals involved in the chain-reaction must differ from each other, and ii) the reaction between radicals and non-radicals must be faster than radical combination reactions. 

These methods are usually highly regio- and stereoselective and represent a breakthrough for synthetic chemistry using radicals. Giese quotes, as an example, that the cyclisation of the 5-hexenyl radical 8 affords the primary cyclopentylmethyl... 

Radical addition reactions conducted by the mercury(II) hydride method were also pioneered by Giese and are very similar in principle to the tin hydride method. The radical is generated from an organomer-curial (rather than a halide) and removed by hydrogen transfer from a mercury(II) hydride (rather than a tin hydride). Mercury(II) hydride reductions have been covered in several recent reviews.3,5,81,82... 

The combination of the catalytic method and the three-phase separation could be applied to the parallel rapid synthesis of a small library of nine compounds of type 7 using the Giese reaction (eq. 5.3). The attractive prospect from this simple experiment arises from the very efficient workup protocol, allowing facile and quantitative separation even if excess reagents... 

Giese and French (1955) have shown how minor features of an absorption curve can be emphasized by differentiation to date, however, the method has not been used in the study of protein or amino acid spectra. Various... 

Substituent steric descriptor calculated from standard enthalpy of formation obtained by computational chemistry using empirical force field methods. It is defined by the following relationship [Beckaus, 1978 Giese and Beckaus, 1978] ... 

---