Stereoselectivity stereocontrol

Apply stereoselective transforms to reduce the number of reactive functional groups, especially those of sufficient reactivity to cause interference with stereocontrolled C-C disconnective transforms. 

Clearable Stereocenter(s). Stereocenter(s) which can be eliminated retrosynthetically by application of a transform with stereocontrol (stereoselectivity). 

Recently, Charette et al. have also demonstrated this behavior in the stereoselective cyciopropanations of a number of enantiopure acyclic allylic ethers [47]. The high degree of acyclic stereocontrol in the Simmons-Smith cyclopropanation has been extended to synthesis several times, most notably in the synthesis of small biomolecules. Schollkopf et al. utilized this method in their syntheses of cyclopropane-containing amino acids [48 a, b]. The synthesis of a cyclopropane-containing nucleoside was also preformed using acyclic stereocontrol [48c]. 

It would be difficult to overestimate the role that the polyether antibiotics have played in the development of organic synthesis, particularly in the area of acyclic stereocontrol. These molecules have inspired many spectacular achievements in organic synthesis, achievements that have dramatically expanded the power and scope of the science. In fact, it would not be inaccurate to attribute much of our understanding about the factors controlling acyclic stereoselectivity for such fundamental processes as hydroboration,5 epox-... 

Ketone 13 possesses the requisite structural features for an a-chelation-controlled carbonyl addition reaction.9-11 Treatment of 13 with 3-methyl-3-butenylmagnesium bromide leads, through the intermediacy of a five-membered chelate, to the formation of intermediate 12 together with a small amount of the C-12 epimer. The degree of stereoselectivity (ca. 50 1 in favor of the desired compound 12) exhibited in this substrate-stereocontrolled addition reaction is exceptional. It is instructive to note that sequential treatment of lactone 14 with 3-methyl-3-butenylmagnesium bromide and tert-butyldimethylsilyl chloride, followed by exposure of the resultant ketone to methylmagnesium bromide, produces the C-12 epimer of intermediate 12 with the same 50 1 stereoselectivity. 

With 2-butenyl- and 3-phenyl-2-propenylstannanes coupling of this Cram selectivity with the intrinsic stereoselectivity of the Lewis acid induced allylstannane-aldehyde reaction gives useful stereocontrol at three contiguous stereogenic centers66,81. 

Successful applications of these stereocontrolled conjugate additions have led to asymmetric syntheses of several natural products such as (+ )-cuparenone (39) which involves formation of a quaternary carbon center81, (- )-/ -vetivone (40)8° and steroidal equilenin 4182 the wavy lines in these structures indicate that C—C bond formed stereoselectively under the influence of a temporarily-attached stereogenic sulfoxide auxiliary group. 

The N,0- and N,S-heterocyclic fused ring products 47 were also synthesized under radical chain conditions (Reaction 53). Ketene acetals 46 readily underwent stereocontrolled aryl radical cyclizations on treatment with (TMSlsSiH under standard conditions to afford the central six-membered rings.The tertiary N,0- and N,S-radicals formed on aryl radical reaction at the ketene-N,X(X = O, S)-acetal double bond appear to have reasonable stability. The stereoselectivity in hydrogen abstractions by these intermediate radicals from (TMSlsSiH was investigated and found to provide higher selectivities than BusSnH. 

The overall transformation of this sequence corresponds to the aldol addition of an aldehyde with a cyclic ketone. The actual aldol addition frequently proceeds with low stereocontrol, so this sequence constitutes a method for stereoselective synthesis of the aldol adducts. The reaction has been done with several Lewis acids, including SnCl4, BF3, and Ti(0-/-Pr)3Cl. 

Recently, a new multicomponent condensation strategy for the stereocontrolled synthesis of polysubstituted tetrahydropyran derivatives was re-published by the Marko group, employing an ene reaction combined with an intramolecular Sakurai cyclization (IMSC) (Scheme 1.14) [14]. The initial step is an Et2AlCl-promoted ene reaction between allylsilane 1-50 and an aldehyde to afford the (Z)-homoallylic alcohol 1-51, with good control of the geometry of the double bond. Subsequent Lewis acid-media ted condensation of 1-51 with another equivalent of an aldehyde provided the polysubstituted exo-methylene tetrahydropyran 1-53 stereoselectively and... 

Diastereoselective conjugate addition of nucleophiles to enones, enals, and enoates occurs with high stereocontrol and constitutes a powerful method in stereoselective synthesis.185... 

Recently, silicon-tethered diastereoselective ISOC reactions have been reported, in which effective control of remote acyclic asymmetry can be achieved (Eq. 8.91).144 Whereas ISOC occur stereoselectively, INOC proceeds with significantly lower levels of diastereoselection. The reaction pathways presented in Scheme 8.28 suggest a plausible hypo thesis for the observed difference of stereocontrol. The enhanced selectivity in reactions of silyl nitronates may he due to 1,3-allylie strain. The near-linear geometry of nitrile oxides precludes such differentiating elements (Scheme 8.28). 

The magnesium initiators (273) and (274) do not display the same stereocontrol as their zinc analogs over the ROP of rac-LA in either CH2C12 or benzene. However, in THF highly heterotactic PLA is produced.826 In non-coordinating solvents the Mg and Zn initiators are believed to adopt dimeric and monomeric resting states respectively, whereas both exist as monomeric forms in THF and hence give rise to similar stereoselectivity. 

Stereoselective synthesis of pseudo C2-symmetrical 1,3-dibenzyldiamino alcohol (S,S) (323) a core unit of HIV protease inhibitors, and the two meso-stereoisomers (323a) and (323b) was achieved by stereocontrolled addition of benzylmagnesium chloride to nitrones (63a) and (63b) (Scheme 2.137). The yield of (S,S)-(323), based on N-Boc-L-phenylalaninal, accounts for 23% (Scheme 2.137) (211). 

According to analogous molecular mechanics analyses,38 this stereoselectivity mechanism would also operate for catalytic systems with oscillating stereocontrol, leading to atactic-isotactic stereoblock polymers,39,40 like those based on two unbridged 2-phenyl-indenyl ligands.40... 

The chain-end stereocontrol for olefin polymerizations leads generally to lower stereoselectivities (differences in activation energy for insertion of the two enantiofaces generally lower than 2 kcal/mol) than the chiral site stereo-control.18131132 For this reason, the corresponding catalytic systems have not reached industrial relevance for propene homopolymerization. However, some of them are widely used for propene copolymerization with ethene. 

The mechanisms of stereoselectivity which have been proposed for chain-end stereocontrolled polymerizations involving secondary monomer insertion also present a general pattern of similarity. In fact, molecular modeling studies suggest that for olefin polymerizations (both syndiospecific and isospecific, Section 4.1.2) as well as for styrene polymerization (syndiospecific, Section 4.2), the chirality of the growing chain would determine the chirality of a fluxional site, which in turn would discriminates between the two monomer enantiofaces. 

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