Alkene geometry control

The Peterson oleflnation presents a valuable alternative to the Wittig reaction. It has the advantage to allow for a simple control of the alkene geometry. Its applicability in synthesis depends on the availability of the required silanes.2... 

Beyond palladium, it has recently been shown that isoelectronic metal complexes based on nickel and platinum are active catalysts for diyne reductive cyclization. While the stoichiometric reaction of nickel(O) complexes with non-conjugated diynes represents a robust area of research,8 only one example of nickel-catalyzed diyne reductive cyclization, which involves the hydrosilylative cyclization of 1,7-diynes to afford 1,2-dialkylidenecyclohexanes appears in the literature.7 The reductive cyclization of unsubstituted 1,7-diyne 53a illustrates the ability of this catalyst system to deliver cyclic Z-vinylsilanes in good yield with excellent control of alkene geometry. Cationic platinum catalysts, generated in situ from (phen)Pt(Me)2 and B(C6F5)3, are also excellent catalysts for highly Z-selective reductive cyclization of 1,6-diynes, as demonstrated by the cyclization of 1,6-diyne 54a.72 The related platinum bis(imine) complex [PhN=C(Me)C(Me)N=Ph]2Pt(Me)2 also catalyzes diyne hydrosilylation-cyclization (Scheme 35).72a... 

The acyclic precursor is an oc, 3-unsaturated amido aldehyde that was condensed with iV-methylhydroxylamine to generate the nitrone ( )-48, which then underwent a spontaneous cycloaddition with the alkene to afford the 5,5-ring system of the isoxazolidinyl lactam 47. The observed product arises via the ( )-nitrone transition state A [or the (Z)-nitrone equivalent] in which the position of the benzyl group ot to the nitrone effectively controls the two adjacent stereocenters while a third stereocenter is predicted from the alkene geometry. Both transition states maintain the benzyl auxiliary in an equatorial position and thus avoid the unfavorable 1,3-diaxial interaction with the nitrone methyl or oxygen found in transition state B. Semiempirical PM3 calculations confirm the extra stability, predicting exclusive formation of the observed product 47. Related cycloadducts from the intramolecular reaction of nitrones containing ester- rather than amide-tethered alkene functionality are also known (83-85). 

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. 

In 2003, Molander reported the synthesis of (+ )-isoschizandrin using the Sml2-mediated 8-endo-trig carbonyl-alkene cyclisation of ketone 71 (Scheme 7.30).69 The axial chirality of the biaryl system efficiently controls the central chirality of the product. The (Z)-alkene geometry is also vital to the stereochemical outcome and the presence of HMPA in the reaction mixture helps control the conformation of the transition state by increasing the steric demands of the alkoxysamarium substituent.69... 

The reaction of azlactones or a Meldrum s acid derivative with 2-phenylbut-3-ene-2-yl acetate, in the presence of the racemic ligand and a palladium source has provided a new method for controlling alkene geometry. By varying the reaction conditions excellent selectivities for either or Z geometry could be obtained. " ... 

Figure 1 illustrates the stereochemical control elements (RIS ElZ) that are operative in this reaction. The x-axis RR) reflects the chair transition states for the enantiomers (174/enr-174 175/enr-175) 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 quadrant to a contiguous one results in the opposite enantiomer of... 

Here is a synthesis of a prostaglandin analogue. Suggest reagents for the steps marked , give mechanisms for those not so marked, and explain any control of alkene geometry. 

Organic structures ch4 Molecules with mirror images Controlling alkene geometry ch31... 

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