"Front Matter". In: Organosilanes in Radical Chemistry - Index of
"Front Matter". In: Organosilanes in Radical Chemistry - Index of "Front Matter". In: Organosilanes in Radical Chemistry - Index of
7 Consecutive Radical Reactions The use of free-radical reactions in multi-step synthesis has steadily increased with time. Indeed, synthetic strategies based on radical reactions have become more and more popular among chemists since a wide selection of functional groups are now available to generate carbon-centred radicals [1]. The knowledge of radical reactivity has increased to such a level as to aid in making the necessary predictions for performing sequential transformations. The predictability has extended to include also the formation of new stereogenic centres, so to render radical reactions of special interest across the field of asymmetric synthesis [1–4]. Stereoselectivities can be dictated by nearby stereocentres, by chiral additives, and by chiral catalysts. As far as the use of silanes as mediators in consecutive radical reactions is concerned, the knowledge of their hydrogen donor abilities coupled with the steric hindrance given by the silicon substituents has contributed substantially in this area, with interesting results in terms of reactivity and stereoselectivity. 7.1 BASIC CONCEPTS OF CARBON–CARBON BOND FORMATION The carbon-centred radical R: resulting from the initial atom (or group) removal by a silyl radical or by addition of a silyl radical to an unsaturated bond can be designed to undergo a number of consecutive reactions prior to H atom transfer. The key step in these consecutive reactions generally involves the inter- or intramolecular addition of R: to a multiple-bonded carbon acceptor. Care has to be taken in order to ensure that the effective rate of the radical addition is higher than the rate of H atom transfer. Standard synthetic planning can be based on the knowledge of rate constants, and coupled with reaction Organosilanes in Radical Chemistry C. Chatgilialoglu # 2004 John Wiley & Sons, Ltd ISBN: 0-471-49870-X
144 Consecutive Radical Reactions conditions, in order to control the concentration of the reducing agent (i.e., a slow addition by syringe pump) or, in the case of intermolecular addition reactions, to have a large excess of the radical acceptor. As an example, the propagation steps for the reductive alkylation of alkenes are shown in Scheme 7.1. For an efficient chain process, it is important (i) that the R 0 3 Si: radical reacts faster with RZ (the precursor of radical R:) than with the alkene, and (ii) that the alkyl radical reacts faster with the alkene (to form the adduct radical) than with the silicon hydride. In other words, the intermediates must be disciplined, a term introduced by D. H. R. Barton to indicate the control of radical reactivity [5]. Therefore, a synthetic plan must include the task of considering kinetic data or substituent influence on the selectivity of radicals. The reader should note that the hydrogen donation step controls the radical sequence and that the concentration of silicon hydride often serves as the variable by which the product distribution can be influenced. Y R• R' 3 SiZ R Y RZ R' 3 Si R' 3 SiH Scheme 7.1 Propagation steps for the intermolecular carbon–carbon bond formation The majority of sequential radical reactions using silanes as mediators for the C w C bond formation deal with (TMS) 3SiH. Nevertheless, as we shall see there are some interesting applications using other silanes, too. The general concepts of stereoselectivity in radical reactions have been illustrated in a number of recent books. Readers are referred to those books for a thorough treatment [1,2]. The following sections deal with a collection of applications where silanes act as mediators for smooth and selective radical strategies, based on consecutive reactions. 7.2 INTERMOLECULAR FORMATION OF CARBON–CARBON BONDS In the initial work, the reaction of cyclohexyl iodide or isocyanide with a variety of alkenes mediated by (TMS) 3SiH was tested, in order to find out the R Y H
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144 Consecutive <strong>Radical</strong> Reactions<br />
conditions, <strong>in</strong> order to control the concentration <strong>of</strong> the reduc<strong>in</strong>g agent (i.e., a<br />
slow addition by syr<strong>in</strong>ge pump) or, <strong>in</strong> the case <strong>of</strong> <strong>in</strong>termolecular addition<br />
reactions, to have a large excess <strong>of</strong> the radical acceptor.<br />
As an example, the propagation steps for the reductive alkylation <strong>of</strong> alkenes<br />
are shown <strong>in</strong> Scheme 7.1. For an efficient cha<strong>in</strong> process, it is important (i) that<br />
the R 0 3 Si: radical reacts faster with RZ (the precursor <strong>of</strong> radical R:) than<br />
with the alkene, and (ii) that the alkyl radical reacts faster with the alkene (to<br />
form the adduct radical) than with the silicon hydride. <strong>In</strong> other words, the<br />
<strong>in</strong>termediates must be discipl<strong>in</strong>ed, a term <strong>in</strong>troduced by D. H. R. Barton to<br />
<strong>in</strong>dicate the control <strong>of</strong> radical reactivity [5]. Therefore, a synthetic plan must<br />
<strong>in</strong>clude the task <strong>of</strong> consider<strong>in</strong>g k<strong>in</strong>etic data or substituent <strong>in</strong>fluence on the<br />
selectivity <strong>of</strong> radicals. The reader should note that the hydrogen donation<br />
step controls the radical sequence and that the concentration <strong>of</strong> silicon hydride<br />
<strong>of</strong>ten serves as the variable by which the product distribution can be <strong>in</strong>fluenced.<br />
Y<br />
R•<br />
R' 3 SiZ<br />
R<br />
Y<br />
RZ<br />
R' 3 Si<br />
R' 3 SiH<br />
Scheme 7.1 Propagation steps for the <strong>in</strong>termolecular carbon–carbon bond formation<br />
The majority <strong>of</strong> sequential radical reactions us<strong>in</strong>g silanes as mediators for the<br />
C w C bond formation deal with (TMS) 3SiH. Nevertheless, as we shall see there<br />
are some <strong>in</strong>terest<strong>in</strong>g applications us<strong>in</strong>g other silanes, too.<br />
The general concepts <strong>of</strong> stereoselectivity <strong>in</strong> radical reactions have been illustrated<br />
<strong>in</strong> a number <strong>of</strong> recent books. Readers are referred to those books for a<br />
thorough treatment [1,2]. The follow<strong>in</strong>g sections deal with a collection <strong>of</strong><br />
applications where silanes act as mediators for smooth and selective radical<br />
strategies, based on consecutive reactions.<br />
7.2 INTERMOLECULAR FORMATION OF CARBON–CARBON<br />
BONDS<br />
<strong>In</strong> the <strong>in</strong>itial work, the reaction <strong>of</strong> cyclohexyl iodide or isocyanide with a<br />
variety <strong>of</strong> alkenes mediated by (TMS) 3SiH was tested, <strong>in</strong> order to f<strong>in</strong>d out the<br />
R<br />
Y<br />
H
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