Syn-stereoselectivity

Such syn stereoselectivity also was observed for a number of additions of nitrones to fluoroallene, such as its reaction with N-phenyl-C-phenyl nitrone [25, 26, 27] (equation 19)... 

Lithium dimethyl and diphenylcuprates add to (phenylsulfonyl)acetylene with complete syn-stereoselectivity leading to -olefins 121. In the case of di-n-butyl and di-s-butylcuprates, 5-20% of Z-olefins 122 are also formed (equation 96)80. 

Tin enolates are also used in aldol reactions.27 Both the Sn(II) and Sn(IV) oxidation states are reactive. Tin(II) enolates can be generated from ketones and Sn(II)(03SCF3)2 in the presence of tertiary amines.28 The subsequent aldol addition is syn selective and independent of enolate configuration.29 This preference arises from avoidance of gauche interaction of the aldehyde group and the enolate P-substituent. The syn stereoselectivity indicates that reaction occurs through an open TS. 

Scheme 2.3 shows reactions of several substituted aldehydes of varying complexity that illustrate aldehyde facial diastereoselectivity in the aldol and Mukaiyama reactions. The stereoselectivity of the new bond formation depends on the effect that reactant substituents have on the detailed structure of the TS. The 3,4-syn stereoselectivity of Entry 1 derives from a Felkin-type acyclic TS. 

In general, BF3 -catalyzed Mukaiyama reactions lack a cyclic organization because of the maximum coordination of four for boron. In these circumstances, the reactions show a preference for the Felkin type of approach and exhibit a preference for syn stereoselectivity that is independent of silyl enol ether structure.119... 

Titanium enolates also can be prepared from /V-acyloxazolidinones. These Z-enolates, which are chelated with the oxazolidinone carbonyl oxygen,128 show syn stereoselectivity, and the oxazolidinone substituent exerts facial selectivity. 

Alkenylzinc reagents can also be made from alkynes by (Cp)2TiCl2-catalyzed hydro-zincation (see Section 4.6).139 The reaction proceeds with high syn stereoselectivity, and the regioselectivity corresponds to relative carbanion stability. 

A deuterium-labeling study of a reaction of this type demonstrated syn stereoselectivity in both the oxypalladation and P-elimination, which indicates that the cyclization occurs by internal migration, rather than by an anti nucleophilic capture.113 This particular system also gives products from double-bond migration that occurs by reversible Pd(II)-D addition-elimination. 

Similarly to peroxycarboxylic acids, DMDO is subject to cis or syn stereoselectivity by hydroxy and other hydrogen-bonding functional groups.93 However a study of several substituted cyclohexenes in CH3CN —H20 suggested a dominance by steric effects. In particular, the hydroxy groups in cyclohex-2-enol and... 

Hydroxy172 and amino173 groups favor syn stereoselectivity. This is similar to the substituent effects observed for peroxy acids and suggests that the substituents may stabilize the TS by hydrogen bonding. 

Alkynes can often be reduced selectively to the alkene by use of the Lindlar catalyst [Pd on CaC03, partly poisoned with Pb(OAc)2]. Here again SYN stereoselectivity is observed despite the fact that this will lead to the more crowded, thermodynamically less stable, cis-alkene, i.e. (52) rather than (53). 

More recently homogeneous hydrogenation catalysts, such as RhCl(Ph3P)3, have been developed which are soluble in the reaction medium. These are believed to transfer H to an alkene via a metal hydride intermediate they, too, lead to a considerable degree of SYN stereoselectivity in hydrogen addition. 

The six-membered rings in these T.S.s are more flexible than the five-membered T.S.—(81) above—and need not be planar (cf cyclohexanes v. cyclopentanes). Elimination may thus proceed, in part at least, from conformations other than the syn-periplanar, with the result that the degree of SYN stereoselectivity in these eliminations may sometimes be lower than that observed in the Cope reaction. Both reactions require higher temperatures than for the Cope reaction, carboxylic esters particularly so. 

The chloroacetoxylation is a quite general reaction and works well with a number of conjugated dienes. Some additional examples are given in Scheme 6 and in equations 15 and 16. The reaction is highly syn stereoselective for a number of cyclic dienes tried. Also, for acyclic dienes the reaction leads to a 1,4 syn addition and the reaction takes place with good stereospecificity (94 -96% syn). Thus (Zi,.E)-dienes give the R R isomer whereas (E,Z)-dienes produce the R S isomer (equations 15 and 16). The reaction has also been extended to include other carboxylic acids than acetic acid (chloroacyloxylation)33d. 

Further variations of the Claisen rearrangement protocol were also utilized for the synthesis of allenic amino acid derivatives. Whereas the Ireland-Claisen rearrangement led to unsatisfactory results [133b], a number of variously substituted a-allenic a-amino acids were prepared by Kazmaier [135] by chelate-controlled Claisen rearrangement of ester enolates (Scheme 18.47). For example, deprotonation of the propargylic ester 147 with 2 equiv. of lithium diisopropylamide and transmetallation with zinc chloride furnished the chelate complex 148, which underwent a highly syn-stereoselective rearrangement to the amino acid derivative 149. 

Steric control has been invoked to explain the kinetic substituent effects as well as the syn stereoselectivity observed in these additions, for example to fraws-cyclooctene and traws-cyclononene. In these cyclic compounds, one side of the TT-bond is more shielded by the rest of the molecule and hence anti attack by a nucleophile is difficult. 

Addition of (TMS)3SiH to a-chiral ( )-alkene 7 was found to take place with a complete Michael-type regioselectivity (Reaction 5.8) [26]. A complete syn stereoselectivity was observed for R = Me, and it was rationalized in terms of Felkin-Ahn transition state 8, which favours the syn product similar to nucleophilic addition. 

Syn stereoselectivity in reduction of acylic chiral ketoxime ethers of type 91 (equation 63) can be obtained using bulky tetramethylammonium triacetoxyborohydride that produces FeUdn-type products with high selectivity . Reaction of a-tolylsulfinylketoximes 92 (equation 64) with L-Selectride also results in syn products 93. 

When TiCl4 is used as the catalyst, the stereoselectivity depends on the order of addition of the reagents. When li-2-butenylstannanc is added to a TiCl4-aldehyde mixture, syn stereoselectivity is observed. When the aldehyde is added to a premixed solution of the... 

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