Alkenes, reductive coupling stability

The reductive coupling of of dienes containing amine groups in the backbones allows for the production of alkaloid skeletons in relatively few steps [36,46,47]. Epilupinine 80 was formed in 51% yield after oxidation by treatment of the tertiary amine 81 with PhMeSiEh in the presence of catalytic 70 [46]. Notably, none of the trans isomer was observed in the product mixture (Eq. 11). The Cp fuMcTIIF was found to catalyze cyclization of unsubstituted allyl amine 82 to provide 83. This reaction proceeded in shorter time and with increased yield relative to the same reaction with 70 (Eq. 12) [47]. Substitution of either alkene prevented cyclization, possibly due to competitive intramolecular stabilization of the metal by nitrogen preventing coordination of the substituted olefin, and resulted in hydrosilylation of the less substituted olefin. 

The above system failed entirely when nonstabilized carbanions such as ketone or ester enolates or Grignard reagents were used as carbon nucleophiles, leading to reductive coupling of the anions rather than alkylation of the alkene. However, the fortuitous observation that the addition of HMPA to the reaction mixture prior to addition of the carbanion prevented this side reaction1 extended the range of useful carbanions substantially to include ketone and ester enolates, oxazoline anions, protected cyanohydrin anions, nitrile-stabilized anions3 and even phenyllithium (Scheme 3).s... 

Examination of various enynes in intermolecular reductive couplings of aldehydes and alkynes illustrated that alkene direction is an effective strategy for controlling regioselectivity. Using conjugated enynes, both NHC/EtaSiH [21] and PRa/EtsB [30] variants proceed with excellent diastereoselectivity favoring addition of the alkyne terminus that is distal to the alkene substituent (Scheme 13). This effect may be derived from predisposition of the alkyne in the orientation 17 that leads to the distal substitution, and increased stability of the jj -stabiUzed metallacycle 18 may also be a factor. 

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... 

The macrocycles of nickel and cobalt that stabilize the metal(I) oxidation state allowing the use of M(II)L/M(I)L couples to be used for the catalytic reduction of alkyl halides [13,14]. With alkyl bromides with alkene and alkyne substituents, the reactions can lead to interesting cyclic molecules by intramolecular coupling [15-17]. 

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