Diastereoselective radical

Radical chemistry has seen tremendous progress in the past two decades and can now be considered as an eminent sub discipline in synthetic organic chemistry [1-6]. Diastereoselective radical chemistry is well established and many examples of enantioselective radical reactions have appeared in the recent literature. For reviews on diastereoselective radical chemistry see [7-11] for reviews on enantioselective radical chemistry see [12-16] and for reviews on conjugate additions, see [17,18]. This review will detail different ways to introduce asymmetry during a radical reaction. These transformations can be broadly classified into atom transfer reactions, reductive alkylations, fragmentations, addition and trapping experiments, and electron transfer reactions. 

Diastereoselective radical cyclizations A= stereocontrol element B = substrate (homogeneous)... 

In addition, 2-substituted chiral succinic acid derivatives can be obtained via diastereoselective radical addition of 2-dioxolanyl radicals to ftimaric acid diamides with a de up to 98% (Scheme 19) [25],... 

D. Crich and L. B. L. Lim, Diastereoselective radical reactions /1-face selective quenching of the l,2-0-isopropylidene-3,4,6-tri-0-benzyl-D-glucopyranos-l-yl radical, Tetrahedron Lett., 32 (1991) 2565-2568. 

Goodall, K. Parsons, A. F. A diastereoselective radical cydization approach to pyrogluta-mates. Tetrahedron Lett. 1997, 38, 491-494. Nachman, R. J. Olsen, J. D. Ranunculin a toxic constituent of the poisonous range plant bur buttercup (ceratocephalus testiculatus). 

A highly diastereoselective radical cascade involving addition of a phenylthiyl radical to a terminal alkyne followed by a [1,5]-hydrogen transfer and a 5-exo-cyclization (g) has been reported (Scheme 112).165... 

Stereoselective reduction of acyclic a-bromo esters.3 Highly diastereoselective radical reduction of a-bromo esters obtains when an electronegative group (F or OCH3) is present at the P-position, particularly at low temperatures. 

Lomolder, R. and Schafer, H.J. (1987) Low-temperature photolysis of peracetylated dodecanoyl peroxides of tartaric acid and D-gluconic acid in the solid state- a diastereoselective radical coupling. Angewandte Chemie, International Edition, 26, 1253-1254. 

F 2-(thiophenyl)vinyl diastereoselective radical acetaldehyde Mannich equivalent... 

Finally, it should be noted that enantiomerically pure derivatives of the Schwartz reagent are very appealing candidates for reagent controlled enantioselective and diastereoselective radical reductions. This is because a plethora of enantiomerically pure zirconocenes are available from other applications in enantioselective catalysis. 

Radical reactions have been recognised only recently for the construction of enantiomerically pure compounds (Renaud and Sibi 2001 Zimmerman and Sibi 2006). In addition to substrate- or auxiliary-induced diastereoselective radical reactions, and in addition to the use of chiral Lewis acids, chiral hydrogen atom donors or chiral transition metal complexes, template molecules can be used to generate a chiral environment and induce chirality to the substrate. With the chiral complexing agent 12, enantioselective radical reactions were achieved with enantiomeric excesses up to 99% ee. 

The mathematical description of this and related reaction schemes are complex and will not be discussed here. To verify the analysis of the stereoselection at the steady state experimentally, diastereoselective radical cyclization reactions were selected. Although face-selective radical cyclizations are much more common than the group-selective counterparts [4], several model compounds were suggested by Curran et al [2]. Molecules which have two radical precursors and one radical acceptor group such as 9 were selected to provide experimental verification... 

Sibi and Ji reported that acyl radicals, generated from acyl bromides, can participate in Lewis acid-mediated diastereoselective radical addition reactions (Scheme 4-26) [49]. Using triethylborane/02 as a radical initiator, the reaction was conducted at -78 °C. 

Diastereoselective radical allylations have been studied in many different contexts, and a plethora of information exists regarding stereocontrol in these reactions. Allylations have been performed using the traditional trapping and )9-elimination sequence occurring typically with allylstannanes as well as a stepwise atom transfer/ elimination sequence found to occur with allylsilanes. Stereochemistry is commonly controlled through the use of chiral auxiliaries or by 1,2-induction, and functionalized anh -aldol and amino acid products are available using this established methodology. 

Another slightly different approach to diastereoselective radical cyclizations uses group transfer methodology in order to access chiral tertiary alcohol moieties commonly found in natural products (Eq. (13.35)) f47J. The reaction occurs anti to the bulky r-butyl group, resulting in the formation of the major product 112. 

Diastereoselective radical additions to hydrazones have been examined under several reaction conditions. The biphasic reaction of a hydrazone with an isopropyl radical in aqueous NH4C1-CH2C12 (4 1, v/v) proceeded slowly to give the corresponding alkyl-substituted derivative in 73% yield and 95% de after being stirred for 22 h (Scheme 7.18).27 As expected, the diastereoselectivity... 

Corminboeuf, Renaud and Schiesser explored the applicability of various quantum methods to the diastereoselective radical cyclization of several bromoacetals during the Ueno-Stork reaction (Scheme 10) [22]. It is interesting to note the performance of the various methods. All of the methods employed correctly predict the anomeric affect (transition states 61, 62 were calculated to lie some 20 kJ mol above 59, 60) and the observed cis stereochemistry [23]. However, only a handful of... 

Chiral dioxolanone 71 and oxazolidinone 72 alkenes, which can be readily prepared from lactic acid or alanine, respectively, undergo diastereoselective radical... 

Lewis Acid-Mediated Diastereoselective Radical Reactions... 

These selected examples show the importance of Lewis acid in diastereoselective radical reactions. Complexation with Lewis acid, in an endocyclic manner or by using extremely bulky metal complexes such as MABR or MAD, reduces the conformational flexibility of intermediate radicals resulting in an improved facial bias. Lewis acid has been shown to effectively enhance facial selectivity by making a temporary ring a to the radical, thus mimicking the exocyclic effect. Radical reactions involving chiral auxiliaries have also benefited from the use of Lewis acid. 

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