Diastereoselective atom transfer addition

Diastereoselective atom-transfer addition reaction of bromoacetate (52) derived from D-xylose as a chiral auxiliary, with 1-hexene initiated by Et3B at — 78 °C proceeds effectively, as shown in eq. 10.25. Treatment of the adduct (53) under basic conditions generates ( -y-butyl-y-lactone with 14%e.e. 

Ytterbium trifluoromethanesulfonate promoted a radical atom-transfer addition of chiral 3-bromoacetyl-2-oxazolidinones to norbornadiene, which afforded the corresponding 5-ex<9-3-bromo-5-nortricycleneacetic acid derivatives in good yields and with high diastereoselectivity (90-96% de, when using the chiral 4-isopropyl- and 4-benzyl-substituted 2-oxazolidinone auxiliaries).133... 

Porter and Mero showed that stereochemical control in atom transfer addition can also be obtained by the use of chiral benzyl oxazolidinone with 1-hexene in the presence of Lewis acid [8]. Excellent diastereoselective control was achieved in the presence of Sc(OTf)3, and the expected R configuration was observed as the major product formed (Scheme 12). 

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. 

Miyabe et al. developed a tandem addition/cycUzation reaction featuring an unprecedented addition of alkoxycarbonyl-stabihzed radicals on oxime ethers [117], and leading to the diastereoselective formation of /1-amino-y-lactone derivatives [118,119]. The reaction proceeds smoothly in the absence of toxic tin hydride and heavy metals via a route involving a triethylborane-mediated iodine atom-transfer process (Scheme 37). Decisive points for the success of this reaction are (1) the differentiation of the two electrophilic radical acceptors (the acrylate and the aldoxime ether moieties) towards the nucleophilic alkyl radical and (2) the high reactivity of triethylborane as a trapping reagent toward a key intermediate aminyl radical 125. The presence of the bulky substituent R proved to be important not only for the... 

A conjugate addition and trapping strategy has emerged as a viable method for forming a chiral center a to a carbonyl by diastereoselective hydrogen atom transfer after initial radical addition to an acrylate. An example shown in Eq. (13.22) uses a C-2 symmetric pyrrolidine chiral auxiliary to induce facial selectivity in the hydrogen atom transfer step [32]. This particular example afforded 89% yield and 25 1 preference for 74. 

Sibi et al. demonstrated for the first time that intermolecular radical addition to a,P-disubstituted substrates (12) followed by hydrogen atom transfer proceeded with high diastereo- and enantioselectivities (Scheme 4.6) [4]. In particular, a chiral bis(oxazoline)s-Mgl2 catalytic system was applied to the enantioselective and highly diastereoselective antijsyn = 99/1) synthesis of anti-aldol-type adducts (13). This is noteworthy because there have been few examples of highly selective methods for preparing anti aldol despite the array of solutions for the synthesis of syn aldol. The key to increasing the reactivity for a,P-disubstituted substrate (12) was N-H imide templates that relieve problems, and the promotion of Lewis acid catalysis via... 

LiC104 was shown to be a more compatible Lewis acid for chelation in an ethereal solvent—when TiCU, a typical chelation agent for a-alkoxyaldehydes, was used in EtaO for alkylation of 79, moderate diastereoselectivity (68 32) was obtained. Rapid injection NMR studies of the TiCU-promoted chelation-controlled Mukaiyama aldol reaction and the Sakurai reaction show that an acyclic transition state must be involved in which the silyl groups never reach the carbonyl oxygen atom. In LPDE-mediated enolsilane additions silylated products predominate. Obviously, the mechanism is different—it is a group-transfer aldol reaction [107]. 

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