Addition reactions—continued stereochemistry

The second chapter, by David A. Oare and Clayton H. Heathcock, deals with the stereochemistry of uncatalyzed Michael reactions of enamines and of Lewis acid catalyzed reactions of enol ethers with a,/ -unsaturated carbonyl compounds. It is effectively a continuation of their definitive review of base-promoted Michael addition reaction stereochemistry that appeared in the preceding volume of the series. 

The cycloaddition of ester enolates with imines is of continuing interest and potassium rert-butoxide may be used to generate the enolate (94S805) but more usually tin, titanium or zinc enolates are employed. When enolates are generated from 2-pyridylthioesters, the stereochemistry of the tin enolate may be greater than and, in some cases, opposite to that for titanium enolates (94T5821). The effect of the lithium, zinc or titanium on the diastereoselectivity in addition reactions of the enolates of a-... 

This chapter and Chapter 10 continue our cataloging of the standard reactions of organic chemistry. To the SnI, Sn2, El, and E2 reactions we now add a variety of alkene addition reactions. Although there are several different mechanisms for additions, many take place through a three-step sequence of protonation, addition, and deprotonation. The following new problems allow you to practice the basics of addition reactions and to extend yourself to some more complex matters. Even simple additions become complicated when they occur in intramolecular fashion, for example. These problems also allow you to explore the influence of resonance and inductive effects, and to use the regiochemistry and stereochemistry of addition to help work out the probable mechanisms of reactions. 

The discussion of the activation of bonds containing a group 15 element is continued in chapter five. D.K. Wicht and D.S. Glueck discuss the addition of phosphines, R2P-H, phosphites, (R0)2P(=0)H, and phosphine oxides R2P(=0)H to unsaturated substrates. Although the addition of P-H bonds can be sometimes achieved directly, the transition metal-catalyzed reaction is usually faster and may proceed with a different stereochemistry. As in hydrosilylations, palladium and platinum complexes are frequently employed as catalyst precursors for P-H additions to unsaturated hydrocarbons, but (chiral) lanthanide complexes were used with great success for the (enantioselective) addition to heteropolar double bond systems, such as aldehydes and imines whereby pharmaceutically valuable a-hydroxy or a-amino phosphonates were obtained efficiently. 

Alkyne hydrosilylation continues as a focus of current research. Despite the relative simplicity of the transformation, it is becoming increasingly clear that different catalysts often utilize unique mechanisms. In addition, the demands placed by the need to access vinylsilanes of differing substitution patterns, stereochemistries, and functional groups require a diverse, complementary set of methodologies. This discussion covers hydrosilylation reactions... 

Cathodic cyclization reactions have supphed and continue to provide a fertile territory for the development and exploration of new reactions and the determination of reaction mechanism. Two areas that appear to merit additional exploration include the application of existing methodology to the synthesis of natural products, and, more significantly, a systematic assessment of the factors associated with the control of both relative and absolute stereochemistry. Until there is a solid foundation to which the non-electrochemist can confidently turn in evaluating the prospects for stereochemical control, it seems somewhat unlikely that electrochemically-based methods will see widespread use in organic synthesis. Fortunately, this comment can be viewed as a challenge and as a problem simply awaiting creative solution. 

Rappoport and co-workers work has continued in a study of the substitution of ( )-and (Z)-/3-bromo- or chloro-styrenes, (1) and (2), by MeS in DMSO-d 6 (sometimes in admixture with CD3OD) as solvent. Product studies indicated retention stereochemistry rate measurements found only a small Br/Cl element effect, slower reactions of the p-OMe bromo compounds, and retardation by CD3OD. These results are consistent with Tiecco s suggestion in 1983 that even this system, activated by only a single phenyl group, reacts through the nucleophilic addition-elimination multistep route. 

FAD. Aside from advances in the methods of analysis, the dramatic increase in the number of enzymes of known stereochemistry has provided additional fuel for the continuing debate over the relative importance of ancestral versus mechanistic explanations for stereochemical trends among enzymes of a given reaction type. 

The addition of hydrogenphosphonates or related compounds to imines or their trimers continues to be a widely employed procedure. Noteable is the observation that whereas the addition of hydrogenphosphonates to (193) require a period of heating at 90 °C for appreciable reaction to occur, sonication of reaction mixtures produces immediate addition to form (194). Interest has tended to be centred around the potential for stereochemical control of the addition through modification to the stereochemistry of the hydrogenphospho-nate or other phosphorus intermediate, or in the use of selected imines. Slight control was observed in the addition of (25,4i )-(195) to (196) the products, (197), exhibited diastereoisomeric ratios of 40-45 60-55. Modest diastereo-selectivity was also observed in reactions between (198) and (199) leading to... 

Because a different stereochemistry for the aza-MBH reaction involving different Michael acceptors was observed, in a continuation of our work, we reinvestigated systematically the reaction of iV-sulfonated imines with various activated olefins, including ethyl vinyl ketone (EVK), acrolein, phenyl acrylate and a-naphthyl acrylate. An interesting inversion of absolute configuration between the adducts derived from MVK or EVK and those from acrolein, methyl acrylate, phenyl acrylate or a-naphthyl acrylate was observed, indicating that the substitution patterns of the olefin may alter or even invert this trend.Similar to the addition to HFIPA, the (3-ICD-mediated addition of methyl, phenyl and naphthyl acrylates 149 to V-sulfonyl imines afforded adducts 150 with an (5) configuration, which is opposite to that observed with aldehydes (Scheme 2.71). ... 

Soum and Fontanille report that di-s-butyl magnesium generates living polymer from 2-vinylpyridine without the involvement of the side-reactions that afflict the polymerization initiated by alkali metal alkyls the resulting polymer has an isotacticity index of 0.9. Arai et al. have synthesized styrene-butadiene-4-vinylpyridine triblock copolymers. Hogen-Esch et a/. have continued their study of the stereochemistry of the anionic polymerization of 2-vinylpyridine in THF solution. Oligomers were synthesized by addition of alkali salts of 2-ethylpyridine to 2-vinylpyridine termination was effected by reaction with methyl iodide. Highly isotactic products were obtained with U and Na as counterions but with K or Rb there was no stereoselection. Epimerization resulted in the expected statistical mixtures of stereoisomers and it was concluded that stereoselection is kinetically controlled. 

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