Heteroatom-substituted Michael Acceptors

To account for the observed diastereoselectivity, a modified Felkin-Anh model has been proposed [18]. In analogy to the classical Felkin-Anh model, originally developed for the addition of organometallic reagents to aldehydes possessing a 

I 6 Copper-mediated Diastereoselective Conjugate Addition and Allylic Substitution Reactions 

R = BOM, = MOM. (TMS = trimethylsilyl, KHMDS = potassium hexamethyidisilazide, MOM = methoxymethyl, DIBAL-H = diisobutylaluminium hydride, Tr = triphenylmethyl, DMAP = 4-N,N-dimethylaminopyridine, TBAE = tetrabutylammonium fluoride, BOM = benzyloxym ethyl) 

A drawback of the Z enoates is usually lower reactivity, reflected in prolonged reaction times and higher reaction temperatures. This may be overcome by switching to more reactive enone systems. Thus, addition of the functionalized cyano-Gilman cuprate system 67 to Z enone 66 proceeded smoothly at low temperatures, with excellent acyclic stereocontrol at the /i-stereocenter [26, 27]. Stereocontrol upon 

This result clearly marks the difficulties and limitations inherent in the modified Felkin-Anh model, which so far is nothing more than a rule of thumb. To account for these results, a switch in mechanism towards a tt-complex model has been proposed [36b, 37]. 

Davis oxaziridine c) MOMCI, f-Pr2NEt, CH2CI2 d) DIBAL-H e) Swern oxidation, f) PhjP-CHC02Me, CH2CI2 g) NaBH4, THF/ H2O h) TrCl, DMAP, CH2Cb i) NaH, Mel, DMF )) TBAF,THF k) CuBr SMe2, MeLi LiBr, 

Sdieme 6.10. Stereoselective cuprate addition to eral 61 -the key step towards the synthesis of olivin. (TBS = t-butyidimethylsilyk IMS = trimethylsilyl) 

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Due to their high conformational flexibility, chiral acyclic Michael acceptors often display low diastereofacial selectivities in copper-mediated conjugate addition reactions.80 Nevertheless, acceptable levels of diastereoselection can be obtained, in particular with heteroatom-substituted Michael acceptors. For example, treatment of the y-benzyloxymethyl-substituted enoate 100 with lithium dimethylcuprate in the presence of chlorotrimethylsilane gives the anti-adduct 101 with excellent diastereoselectivity (Scheme 26). a Products of this type can be easily... 

Conjugate addition reactions of acyclic Michael acceptors possessing heteroatom-substituted stereogenic centers in their y-positions may provide useful levels of diastereoselectivity. A typical example is given with the y-alkoxy-substituted enoate 49 in Scheme 6.8 [17]. High levels of diastereoselectivity in favor of the anti addition product 50 were found in the course of dimethylcuprate addition. 

The complex [Os(NH3)5(q -benzene)] reacts with both acetals and Michael acceptors to form benzenium intermediates [28]. These intermediates are difficult to isolate but are readily characterized at -40 °C. In contrast to the arenium complexes derived from heteroatom substituted benzenes, and NMR data indicate that the benzenium ring is trihapto-coordinated. The benzenium complexes react with a silyl ketene acetal, a silyl enol ether, or aryl lithium to yield substituted 1,4-cyclohexadiene complexes [21]. The 1,4-cyclohexadiene... 

Besides the Michael addition of heteroatomic nucleophiles initiating cyclocondensations, acceptor substituted unsaturated systems can also be reacted with carbon nucleophiles stemming from aldehydes in the sense of an umpolung, generally referred to as the Stetter reaction [244-246]. This process is organocatalytic and furnishes in turn 1,4-dicarbonyl compounds, intermediates that are well suited for Paal-Knorr cyclocondensations giving rise to furans or pyrroles. Among numerous heterocycles furans and pyrroles have always been the most prominent ones since they constitute important classes of natural products [247-249], of synthetic... 

The conjugate addition of oxygen nucleophiles to acceptor-substituted olefins is the oxa-Michael reaction (Scheme 15). The term is derived from heteroatom replacement nomenclature, meaning that oxygen takes the place of a CH2 unit (RCH2 RO ). Oxa-Michael reactions have been known for many years and are often catalyzed by bases or acids [7]. Catalysis by metals has been reported sporadically in the older literature, e.g. for the case of alcohol addition to vinyl ketones with a Nieuwland catalyst (HgO, BF3-OEt2, ROH) [75-77]. A patent describes a PdCl2-catalyzed addition of alcohols to acrolein or methacrolein [78]. 

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