E/Z geometry control

Rearrangement of allyl trimethylsilyl ketene acetal, prepared by reaction of allylic ester enolates with trimethylsilyl chloride, to yield Y,5-unsaturated carboxylic a-cids. The Ireland-Claisen rearrangement seems to be advantageous to the other variants of the Claisen rearrangement in terms of E/Z geometry control and mild conditions. 

The enolate geometry can be controlled, in the case of esters, by the addition of HMPA without HMPA the enolate has predominantly the. E-geometry, while with HMPA mainly Z-geometry is observed. Similar additions with magnesium and zinc enolates are observed24"32 373 374. 

If a stereogenic double bond is established by this Elcb elimination, one usually observes a trans- or an / -sclcctivity. This experimental finding could have two origins (1) product development control (Section 4.1.3), if the stereoselectivity occurs under kinetic control, or (2) thermodynamic control. Thermodynamic control comes into play if the cis, trans- or E,Z-isomeric condensation products can be interconverted via a reversible 1,4-addition of NaOH or KOH. In the trans- or isomer of an ce,/l-un saturated carbonyl compound the formyl or acyl group may lie unimpeded in the plane of the C=C double bond. This geometry allows one to take full advantage of the resonance stabilization C=C—0=0 <-> C—C=C—0 . ... 

The control of alkene geometry in RCM reactions has been an area of intense research and interest since the process was first developed. While a general solution to this challenge has not yet been developed, intriguing observations of E Z control in macrocyclizations continue to be reported. For example, in the course of their studies on the synthesis of herbarumin I and II, Fiirstner and co-workers reported the selective formation of either of the two isomeric alkene products 16 or 17 via RCM of diene 15 <02JA7061> (Scheme 8). The diene 15 was transformed into the -alkene 17 using the ruthenium indenylidene catalyst (Fiirstner Metathesis Catalyst FMC, <01MI4811>) while use of the MC2 led to clean formation of the Z-isomer 16. 

Synthetic analogues of this compound, such as the trienes, are also effective at arresting insect development, providing that the double bond geometry is controlled. The Z,E,E geometrical isomer of the triene is over twice as active as the , ,E-isomer, and over 50 times as active as the ,Z,Z- or Z,E,Z-isomers. 

Disubstituted ( , )- ,3-alkadienes react more easily with dicnophiles than the corresponding (E,Z)- and (Z.Z)-dienes, since minor steric interactions are present in the s-cis conformation required for the concerted [4 + 2] cycloaddition. The syn/anti (simple) diastereoselectivity is controlled by the geometry of the diene. Only the r/.v-l,2,3,6-tetrahydro-3,6-diphenylpyri-dazine derivatives 1 and 2 are obtained by cycloaddition of4-phenyl-3/7-l,2,4-triazole-3,5(47/)-dione4 and alkyl diazenedicarboxylates5-8 to (E,E)-, 4-diphenylbutadiene ( HNMR)9-13. 

Figure 1 illustrates the stereochemical control elements (R/S E/Z) that are operative in this reaction. The jc-axis (R reflects the chair transition states for the enantiomers (174/e/if-174 llS/ent-llS) of the vinyl ethers of Ae ( )- and (Z)-alcohols the y-axis reflects the change of alkene geometry of a given absolute configuration. Passage from one quadi t to a contiguous one results in the opposite enantiomer of... 

Introduction and stereochemical control syn,anti and E,Z Relationship between enolate geometry and aldol stereochemistry The Zimmerman-Traxler transition state Anti-selective aldols of lithium enolates of hindered aryl esters Syn-selective aldols of boron enolates of PhS-esters Stereochemistry of aldols from enols and enolates of ketones Silyl enol ethers and the open transition state Syn selective aldols with zirconium enolates The synthesis of enones E,Z selectivity in enone formation from aldols Recent developments in stereoselective aldol reactions Stereoselectivity outside the Aldol Relationship A Synthesis ofJuvabione A Note on Stereochemical Nomenclature... 

Stereoselectivity is at first sight the easiest of the three selectivities to understand and the most difficult to exercise. It simply means control over stereochemistry. More precisely it means the control over new stereochemistry. In many reactions, whether new carbon-carbon bonds are being formed or whether some functional group is merely being altered, stereochemistry appears. It may be that a double bond is formed which can have E or Z geometry, or that a new stereogenic centre is formed, perhaps by reduction of a ketone, and therefore a relationship develops with other stereogenic centres in the molecule. If these aspects are controlled then we have stereoselectivity. 

The red R group may seem to get in the way of the reaction but, of course, the dienophile is not approaching in the plane of the diene but from underneath. It is difficult to find a convincing example of this stereochemistry as there are so few known, partly because of the difficulty of making E,Z dienes. One good approach uses two reactions you met in Chapter 29 for the control of double-bond geometry. The cis double bond is put in first by the addition of methanol to butadiyne and the trans double bond then comes from LiAlH4 reduction of the intermediate acetylenic alcohol. 

Saito H, Sivagum J, Jockusch S et al (2007) Controlled diastereoselectivity at the alkene-geometry through selective encapsulation E-Z photoisomerization of oxazolidinone-functionalized enecarbamates within hydrophobic na o-cavities. Chem Commun 43 819-821... 

Piers and Morton have reported that lithium (phenylthio)(trimethyl-stannyOcuprate smoothly transfers one trimethylstannyl group to a,/3-acetylenic esters in a conjugate sense to give /3-trimethylstannyl-a,/3-olefinic esters. Importantly, products of almost exclusive E- or Z-geometry are formed under conditions of kinetic or thermodynamic control. Partial reduction followed by Wittig... 

---