Stereoselective synthesis electrophilic reactions

The aziridines are the nitrogen analogs of the epoxides and undergo similar electrophilic reactions. No biological data were obtained for these compounds nor were they used as precursors to any CA-4, 7, analogs. They have been included since the synthesis is noteworthy, and they could be interesting intermediates. Xu et al. stereoselectively aziridinated chalcones using the nitrene precursor (PhINTS) and a copper catalyst to form compound 141 (Scheme 36) [82],... 

Recently, the semi-synthesis of Vancomycin (48) on solid supports was accomplished using an allylic linker (Scheme 3.2) [123, 124]. Polymer-bound chiral electrophilic selenium reagents have been developed and applied to stereoselective se-lenylation reactions of various alkenes (Tab. 3.9) [125]. 

Many uses of the sulfolene reaction for synthetic purposes are associated with this easy stereoselective synthesis of conjugated dienes [109, 203]. The development of this methodology led to new routes for the introduction of electrophiles in the 2 and (or) 5 positions of the sulfolenes... 

The higher homologue of 3-sulfolene, 2,7-dihydrothiepin-l,1-dioxide could be similarly metallated at low temperatures. Reaction with reactive electrophiles followed by extrusion of sulfur dioxide led [549] to the corresponding hexatriene derivatives, as in the stereoselective synthesis of (Z,E)-l,3,5-decatriene (considered as an undecatriene in the publication) shown here. 

More recently a stereoselective synthesis of (35)-7V-Pf-3-aminoaspartate (Pf = 9-phenylfluoren-9-yl) by reaction of TV-Pf-aspartate enolates with electrophilic animating reagents was reported by Sardina and co-workers [40]. Electrophilic animations were run using trisylazide or dialkylazodicarboxylates DTBAD and DBAD. N-Pf-... 

Various functionalized alkynes can be submitted to carbocupration reactions, such as alkoxyalkynes,150 alkynyl carbamates,151 acetylenic orthoesters,152 and thioalkynes.153 The carbocupration of orthoesters, for example, 204, has been used to prepare a-substituted esters of the type 206 by acidic hydrolysis of the adduct 205 (Scheme 51).152 This allows the formation of regioisomers that are not accessible by copper-mediated addition to acetylenic esters. A stereoselective synthesis of trisubstituted alkenes has been described by Normant et al.lSd> starting from phenylthio-acetylene 207. Carbocupration with lithium di- -butylcuprate affords the intermediate 208 which, upon addition of /z-butyllithium, undergoes a 1,2-metalate rearrangement to the vinylcuprate 209. The latter can be trapped with various electrophiles, for example, ethyl propiolate, providing product 210 with complete regio- and stereocontrol. 

Allylic alcohols can serve as 7t-allyl cation precursors to act as electrophiles in Sn reactions with a tethered O-nucleophile giving rise to the formation of spiroannulated tetrahydrofurans <2000TL3411>. Michael acceptors are also suitable electrophiles for the cyclization to tetrahydrofuran rings <2003T1613>. The Tsuji-Trost allylation has found widespread application in the synthesis of carbo- and heterocyclic compounds. Allylic substitution has been employed in the stereoselective synthesis of 2-vinyl-5-substituted tetrahydrofurans <2001H(54)419>. A formal total synthesis of uvaricin makes twofold use of the Tsuji-Trost reaction in a double cyclization to bis-tetrahydrofurans (Equation 73) <20010L1953>. 

The regiochemistry of the hydrozirconation of acetylenic selenides with the Schwartz reagent [Cp2Zr(H)Cl] is dependent on the nature of the substituents. For simple acetylenic selenides (R = Ar, n-Bu), ( j-j9-zirconated vinyl selenides were formed exclusively. The reaction with electrophilic reagents has allowed the stereoselective synthesis of ( j-2-halovinylaryl selenides [75], (Ej-2-aryl-vinyl aryl selenides [76], ( , j-l-arylselanylbutadienes [77] and ( j-2-butyltel-luranylvinyl selenides [78] (Scheme 55). 

Here is a simple example in the field of prostaglandin synthesis where 9-BBN was used on a protected optically active propargyl alcohol.12 The starting material is identical to the alkyne 78 that we reacted with Bu3SnH above and the result is the same - cis hydrometallation with the metal atom at the terminus. However that was a thermodynamically controlled stereoselective radical chain reaction while this is a kinetically controlled stereospecific electrophilic addition to give the vinyl borane -87. 

It is clear that the addition reactions of enol ethers to C—ir-bonds are useful transformations in organic synthesis. Selectivity can be exercised with a range of enol ethers, with the proper choice of catalysts, and with a range of carbon electrophiles. The question of stereoselectivity of these reactions will be discussed in the next chapter. In the future, we can expect more new developments in this area including a better understanding of the structural and mechanistic details of these reactions. ... 

The Rubottom oxidation has found widespread application in organic synthesis. A few recent examples of the use of this methodology for the construction of complex molecules are described below. As noted above, the stereoselectivity in these reactions is usually controlled by steric effects, which dictate the face-selectivity of the epoxidation step. The chemoselectivity is generally controlled by electronic effects, as the electrophilic oxidants react more rapidly with the electron-rich enol ether than with other double bonds in the substrate. 

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