Alkenes, reductive coupling stereochemistry

A much more highly diastereoselective process results when alkenic 3-keto ester and 3-ketoamide substrates can be utilized in the ketone-alkene reductive coupling process. Both electron deficient and unactivated alkenes can be utilized in the reaction (equations 65 and 66). In such examples, one can take advantage of chelation to control the relative stereochemistry about the developing hydroxy and car-boxylate stereocenters. Favorable secondary orbital interactions between the developing methylene radical center and the alkyl group of the ketyl,and/or electrostatic interactions in the transition state account for stereochemical control at the third stereocenter. 

Curiously, the relative stereochemistry between the carboxylate and the adjacent hydroxy group in the Sml2-mediated intramolecular pinacolic coupling reaction is opposite to that observed in the intramolecular Barbier reactions and ketone-alkene reductive coupling reactions discussed previously (compare... 

Procter has suggested that a study of the dependence of reaction outcome on the stereochemistry of the alkene in the substrate can be used to gain information on the mechanistic direction of reductive couplings.42,43 In cases where the alkene stereochemistry has a marked effect on the reaction outcome, a traditional carbonyl first mechanism may be in operation, whereas in reactions where alkene stereochemistry has little effect, an alternative mechanism in which the alkene is reduced first and a common reactive intermediate is formed, regardless of the geometry of the starting alkene, may operate (Scheme 5.20).42,43... 

The imide 189 is easily made from protected tartaric acid 190 and the vinyl silane 188 coupled in a Mitsunobu reaction. Reduction of one of the carbonyl groups of the imide 191 may seem tricky but the molecule is C2 symmetric so the two carbonyl groups are the same and once one is reduced the molecule is a much less reactive amide. The stereochemistry of the acetate in 192 does not matter as it disappears in the cyclisation to 186. Notice that the alkene geometry is retained. 

In its original form,94 the Julia reaction consisted of the formation of a carbon-carbon double bond through the coupling of a sulfonyl-stabilized anion and a carbonyl compound to generate a P-hydroxy sulfone, followed by a reductive elimination to afford the alkene (Eq. 47). A subsequent study of its scope and stereochemistry led to improved reaction conditions, which are now widely used.206 Alternative methods to synthesize the P-hydroxy sulfone intermediates, such as the addition of sulfonyl carbanions to esters with subsequent reduction of the ketone to the P-hydroxy sulfone, are also known (Eq. 121).207... 

Suzuki-Miyaura cross-coupling polymerization of 1,4-bis((Z)-2-bromovinyl)benzenes with aryl-bis-boronic acids. The interest has been in an alternative approach, where rather than building a PPV with a pre-ordained stereochemistry, a postpolymerization yyn-selective reduction on a poly(phenylene ethynylene) (PPE) is used [125]. This scheme has the advantage that high molecular weight PPEs can be synthesized using either Pd-catalysis or alkyne metathesis. This route could also potentially allow for the access to an additional array of PPVs that are uniquely accessible from PPEs. The transformation of the triple bonds in PPEs and other acetylene building blocks to alkenes has considerable potential. 

Vares and Rein have developed a powerful approach to tetrahydrofurans where they coupled an asymmetric Homer-Wadsworth-Emmons (HWE) reaction with a Pd-catalyzed ring closure to generate cis- and tran -tetrahydrofuran derivatives (Schemes 76 and 77) [82]. From weso-dialdehyde 289, asymmetric HWE gave E-alkene isomer 291 with high levels of diastereoselectivity. Aldehyde reduction was followed by pivaloyl migration to afford cyclization precursor 292 in 63 % yield. Pd-catalyzed ir-allyl formation and cyclization proceeded with overall retention of stereochemistry to give 2,5-cis-tetrahydrofuran 293 in 76 % yield. 

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