Oxygen nucleophiles, addition stereoselectivity

The model correctly predicts (rationalizes) the observed preference for formation of Ae anti raAer than Ae syn product in the cycloaddition reactions of a wide variety of chiral allylic eAers, Aus successfully laying to rest years of frustrated discussion. - It also correctly predicts Aat as Ae size of R increases (Me - Ph < Et < Pr < Bu ), Ae preference for transition state structure (18 ) should increase leading to enhanced anti stereoselectivity (Table 15). At first, Ais prediction seems strange. However, once it is realized Aat, like Ae Felkin-Anh model for nucleophilic addition to a carbonyl, Ae outside position is actually more sterically demanAng Aan Ae inside, Aen Ae prediction is sensible on purely steric grounds. Thus, Ae angle d approach of Ae nitrile oxide oxygen to Ae alkene actually places it nearer Ae outside Aan Ae inside substituent located at Ae allylic carbon. ... 

Elsewhere in this chapter we have used oxygen nucleophilic processes to illustrate stereoselectivity (Sections II.B and II.C), coelectrophiles (Section I.A), etc. and shall not repeat these here. The literature of oxygen nucleophile attacks on alkynes includes trends in substituent effects but the data are often qualitative and usually scattered. Numerous examples indicate that the reactions of alkoxides with C2H2 are relatively slow and that most substituents facilitate the addition (Tables 13 and 14) ... 

The enantioselective nucleophilic addition of prochiral C=0 and C=N moieties to the corresponding saturated chiral products is one of the most important stereoselective transformations on both the laboratory and the industrial scale. Although, over the past few decades, remarkable scientific achievements have been made in these research areas by using a variety of transitional metal-based catalysts, the sensitivity of the reaction to moisture and oxygen, as well as the toxic metal contamination of the product, usually restrict its practical application. Thus, currently, there is much interest in chiral organocatalysts, as they tend to be less toxic and more environmental friendly than traditional metal-based catalysts [1]. They are usually robust and thus tolerate moisture and oxygen, so that they usually do not demand any special reaction conditions. 

Few further examples exist concerning the intermolecular addition of oxygen nucleophiles to a,P-unsaturated sulfoxides [72,118,119] however, several reports have been made concerning the stereoselective intramolecular conjugate addition of oxygen nucleophiles to a,P-unsaturated sulfoxides [55,56,120-122]. Solladie and Moine [55] reported the highly stereoselective formation of the chromene (150) in 96% yield from the hydroquinone (149) on treatment with sodium methoxide in refluxing methanol (Scheme 5.50). 

Nonperpendicular attack of the nucleophile explains Felkin s hypothesis for the predominance of interactions involving R1 and R2 over interactions involving the carbonyl oxygen. Additionally, as R1 increases in bulk, the nucleophile is pushed towards the stereogenic center and can better feel" the difference between the substituents, resulting in an increase in stereoselectivity. 

Hassner and coworkers have developed a one-pot tandem consecutive 1,4-addition intramolecular cycloaddition strategy for the construction of five- and six-membered heterocycles and carbocycles. Because nitroalkenes are good Michael acceptors for carbon, sulfur, oxygen, and nitrogen nucleophiles (see Section 4.1 on the Michael reaction), subsequent intramolecular silyl nitronate cycloaddition (ISOC) or intramolecular nitrile oxide cycloaddition (INOC) provides one-pot synthesis of fused isoxazolines (Scheme 8.26). The ISOC route is generally better than INOC route regarding stereoselectivity and generality. 

Stereoselective Michael additions of carbon-, nitrogen-, oxygen-, and sulfur-centered nucleophiles to 6,7-dehydro-5-oxoindolizidine have been reported <2006JOC6630>. 

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