Electrophiles diastereoselectivity

Some headway has been made using sulphoxides to direct the lithiation of arenechromium tricarbonyls in the manner of Kagan s work with ferrocenes . Diastereoselectiv-ities in the lithiation-quench of 392 are excellent, though yields are poor with most electrophiles. Diastereoselectivity reverses on double lithiation, because the last-formed anionic site in 394 is the most reactive (Scheme 163). 

Ortho-lithiation of an O-protected m-fluorophenol, followed by treatment with phosphorus tribromide and aqueous acid deprotection, has given the phosphino-phenol 18. In the presence of potassium t-butoxide in an aprotic solvent, this is converted into the non-planar system 19, which exhibits pyroelectric properties. An organolithium route to the alkynylphosphine 20 has been developed. The same paper also reports a new route to the lithiated alkynylphosphine 21 and a study of its reactivity towards electrophiles. Diastereoselective lithiation of... 

In the Held of chiral electrophiles, diastereoselective additions of enolsilanes to chiral a-fluoro-a-methyl-P-alkoxy aldehydes, a-methyl aldehydes, a-alkoxy aldehydes, a,p-dialkoxy aldehydes and a-methyl-P-alkoxy aldehydes were reported to proceed with good stereocontrol following Felkin-Anh or chelation models (c/. Section 2.4.4.1). Very good selectivities were reported in the addition of enolsilanes to chiral imines, particularly those derived from carbohydrates (Scheme 17 and 18).i. 6... 

Unlike regular aziridine-2-carboxylic esters, aziridine-2-carboxylic thioester 174 (Scheme 3.62) forms stable carbanions at the 2-position upon treatment with base [13b, 122]. Thus, electrophilic alkylations of aziridine 174 afforded products 175. The reactions were highly diastereoselective, affording 175 in moderate to good... 

Enantiopure methyleneaziridine 248 could be lithiated and subsequently trapped with a variety of electrophiles in a highly diastereoselective manner (Scheme 5.63) [89]. 

Addition reactions of the a-seleno lithium reagent 26 to carbonyl compounds have been undertaken 27. The a-seleno lithium reagents are configurationally labile at — 78 °C 27 28 and, therefore, the diastereoselectivity observed with 26 ( 90 10) does not significantly depend on the nature of the electrophile but rather reflects the thermodynamic ratio of the diastereomeric lithium compounds. 

Double deprotonation of tetrahydro-2-(2-nilroethoxy)-2//-pyran (8) and reaction with electrophiles provides a variety of substituted and functionalized nitroaldols1 Reaction with aldehydes affords 2-nitro-l,3-alkanediols 9 in 44 90% yield and high diastereoselectivities. From analogy of their II-NMR spectra and comparison with known compounds, the (R, R ) relative configuration is likely15. 

This section describes Michael-analogous processes in which, mostly under electrophilic conditions, ally - or alkynylsilanes undergo addition to enones or dienones (Sakurai reactions). The intramolecular addition of allylsilanes is an extremely useful reaction especially for the construction of carbocyclic ring systems, which occurs in a diastereoselective manner, in many cases with complete asymmetric induction. 

The enolate of the 1,4-adduct, obtained after the stereoselective Michael addition step, as discussed in the previous sections, may be quenched in situ with various electrophiles. The fact that additional stereogenic centers may be formed via such tandem Michael addition/quench-ing procedures, giving products with high diastereoselectivity in many cases, extends the scope of these methods substantially. Furthermore these procedures occasionally offer the possibility of reversing the syn/anti diastereoselection. In the next sections pertinent examples of diastereoselective inter- and intramolecular quenching reactions will be discussed. 

When the cyclic enone is unsubstituted, but the resulting enolate is quenched with an electrophile under conditions of kinetic control the irons adduct is formed exclusively303. Particularly successful is the sequential Michael addition/enolate alkylation in diastereoselective routes to frans-a,/j-difunctionalized cycloalkanones and lactones304-308. The key steps in the synthesis of methyl ( + )-jasmonate (3)309-310 (syn/anti diastereoselection) and (-)-khushimone (4) (syn/anti and induced diastereoselection) illustrate this sequence311 (see also Section D. 1.1.1.3.). 

The use of enantiomerically pure (R)-5-menthyloxy-2(5.//)-furanone results in lactone enolates, after the initial Michael addition, which can be quenched diastereoselectively trans with respect to the /J-substituent. With aldehydes as electrophiles adducts with four new stereogenic centers arc formed with full stereocontrol and the products are enantiomerically pure. Various optically active lactones, and after hydrolysis, amino acids and hydroxy acids can be synthesized in this way317. 

The electrophilic carbene carbon atom of Fischer carbene complexes is usually stabilised through 7i-donation of an alkoxy or amino substituent. This type of electronic stabilisation renders carbene complexes thermostable nevertheless, they have to be stored and handled under inert gas in order to avoid oxidative decomposition. In a typical benzannulation protocol, the carbene complex is reacted with a 10% excess of the alkyne at a temperature between 45 and 60 °C in an ethereal solvent. On the other hand, the non-stabilised and highly electrophilic diphenylcarbene pentacarbonylchromium complex needs to be stored and handled at temperatures below -20 °C, which allows one to carry out benzannulation reactions at room temperature [34]. Recently, the first syntheses of tricyclic carbene complexes derived from diazo precursors have been performed and applied to benzannulation [35a,b]. The reaction of the non-planar dibenzocycloheptenylidene complex 28 with 1-hexyne afforded the Cr(CO)3-coordinated tetracyclic benzannulation product 29 in a completely regio- and diastereoselective way [35c] (Scheme 18). 

Negishi E, Tan Z (2005) Diastereoselective, Enantioselective, and Regioselective Carbo-alumination Reactions Catalyzed by Zirconocene Derivatives. 8 139-176 Netherton M, Fu GC (2005)Pa]ladium-catalyzed Cross-Coupling Reactions of Unactivated Alkyl Electrophiles with Organometallic Compounds. 14 85-108 Nicolaou KC, King NP, He Y (1998) Ring-Closing Metathesis in the Synthesis of EpothUones and Polyether Natmal Products. 1 73-104 Nishiyama H (2004) Cyclopropanation with Ruthenium Catalysts. 11 81-92 Noels A, Demonceau A, Delaude L (2004) Ruthenium Promoted Catalysed Radical Processes toward Fine Chemistry. 11 155-171... 

Deprotonation of allylic aryl sulfoxides leads to allylic carbanions which react with aldehyde electrophiles at the carbon atom a and also y to sulfur . With benzaldehyde at — 10 °C y-alkylation predominates , whereas with aliphatic aldehydes at — 78 °C in the presence of HMPA a-alkylation predominates . When the a-alkylated products, which themselves are allylic sulfoxides, undergo 2,3-sigmatropic rearrangement, the rearranged compounds (i.e., allylic sulfenate esters) can be trapped with thiophiles to produce overall ( )-l,4-dihydroxyalkenes (equation 24). When a-substituted aldehydes are used as electrophiles, formation of syn-diols 27 occurs in 40-67% yields with diastereoselectivities ranging from 2-28 1 (equation 24) . ... 

As discussed previously, West and coworkers developed a two-step domino process, which is initiated by a Nazarov reaction. This can be extended by an electrophilic substitution. Thus, reaction of 1-179 with TiCl4 led to 1-182 via the intermediate cations 1-180 and 1-181. The final product 1-183 is obtained after aqueous workup in 99% yield (Scheme 1.43) [23]. It is important to mention here that all six stereocenters were built up in a single process with complete diastereoselectivity hence, the procedure was highly efficient. 

Lithiation of to form 184 was reported by the Harmata group to be the first example of a sulfoximine-stabilized vinyl carbanion. The resulting organolithium species 184 reacted with various electrophiles to supply structurally diverse benzothiazines <88TL5229>. However, the diastereoselectivity of the reactions with aldehydes was low (Scheme 48). 

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