Regioselective reductive coupling

Table 22.8 Regioselective reductive coupling of non-symmetric 1,3-diynes to various a-ketoaldehydes.

Synthetically useful ft, y-8, e-doubly-unsaturated quaternary carbinols have been prepared enantioselectively via regioselective reductive coupling of 1,3-enynes with... 

Zhu S, Lu X, Luo Y, Zhang W, liang H, Yan M, Zeng W (2013) Ruthenium(II)-catalyzed regioselective reductive coupling of a-imino esters with dienes. Org Lett 15 1440-1443... 

Keywords Ynoates, aldehydes, triethylsilane, Ni(COD>2, SIPr.HBF4, KO Bu, PPh3, THF, room temperature, regioselective reductive coupling, multicomponent reaction (MCR), silyl-protected Y-hydroxy-a,p-enoates... 

Cyclization of 2-(l-alkynyl)XV-alkylidene anilines is catalyzed by palladium to give indoles (Equation (114)).471 Two mechanisms are proposed the regioselective insersion of an H-Pd-OAc species to the alkyne moiety (formation of a vinylpalladium species) followed by (i) carbopalladation of the imine moiety and /3-hydride elimination or (ii) oxidative addition to the imino C-H bond and reductive coupling. 

Moreover, propargyl oxiranes 202 were found to react with samarium diiodide and ketones to form a,a -dihydroxyallenes 203 with moderate to high anti-diastereo-selectivities (Scheme 2.62). Aurrecoechea and co-workers [99] reported this reductive coupling to proceed smoothly in the absence of a palladium catalyst, i.e. a direct electron transfer from the samarium(II) to the substrate has to take place in order to generate an allenyl/propargyl samarium intermediate of type 184/185, which is then regioselectively trapped by the electrophile. 

Regioselective syntheses of 1,3,5-unsymmetrically substituted benzenes (309) are catalyzed by Pd(dba)2/PPh3 mixed alkyne/diyne reactants give mixtures containing homocoupled and mixed products (24 21 from HC CPh + HC=CC= CC Hn). The probable mechanism involves oxidative addition to the Pd(0) center, insertion of the second diyne into the Pd—H bond, reductive coupling and subsequent jr-complexation of this product to Pd(0), followed by Diels-Alder cycloaddition of the third diyne and elimination of product. 

Unusual regioselectivity has been observed180 during the reductive coupling of alkynes and allenes by hydrozirconation and zinca-Claisen rearrangement. 

Reductive couplings of 1,6-enynes and aldehydes, catalysed by Ni(cod)2, show regioselectivity effects that are switchable via addition of a phosphine.198 Chelation (g) control and steering effects due to the alkene tether have been invoked to explain this. 

Chiral 1,6-enynes (109, X = O or CH2) undergo nickel-catalysed reductive coupling with aldehydes to give regioisomers, 110a and 110b regioselectivity is 95 5, with a... 

The Ni(dppe)Br2-catalyzed condensation of oxabenzonorbomadienes with either p-iodo-(Z)-propenoates or o-iodobenzoate provided a new synthesis of aimulated coumarins. As shown below, this reaction was also found to be regioselective <030L4903>. The same group also reported the reductive coupling of oxabenzonorbomadienes and 7-oxanorbomenes with various propiolates under similar Ni-catalyzed conditions at room temperature <03CEJ3165>. 

Substituted 1,4-dienes are obtained by reductive coupling of allenes and 1-alkynes via hydrozirconation of the allenes. Greatly enhanced regioselectivity is attained by using methoxyaluminoxane as catalyst. 

Titanium complexes derived from ethylene-bridged 2-indenyl ligands (Scheme 650) have been prepared by reductive dehydroxy coupling of 2-(hydroxymethyl)indenes with low-valent titanium compounds. Alkyl substitution of the indene ring at C(3) improves the regioselectivity of the reductive coupling.1671... 

Figure 4. Regioselective Oxidative Coupling The final step for the completion of the pentacyclic ring system of the morphine alkaloids involves the closure of the C4-C5 ether bridge. Synthetic salutaridine has been transformed in vivo to thebaine, codeine, and morphine in Papaver sominiferum. Reduction of the dienone was proposed,30 and indeed, hydride reduction of salutaridine produces a mixture of two epimeric alcohols. However, upon feeding 7-3H labelled salutaridinol epimers to Papaver somniferum, only the S-isomer was converted into thebaine an indication that the reaction is enzyme mediated.31 >32 This finding contradicted earlier work by Barton in which the configuration of the alcohol was assigned as R (See description of Barton s synthesis, ref. 50).

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