Conjugate addition alanate

Irrespective of the stereochemistry of the ot,p-enones, lithium alkenyltrialkylalanates, e.g. (28) and (29), obtainable by treatment of alkenylalanes with methyllithium (or n-butyllithium), are also excellent 1,4-conjugate alkenyl transfer reagents. The cornerstone of a general prostaglandin synthesis, as exemplified in Scheme 6, employs the alanate conjugate addition process exclusively.13... 

K. F. Bernady and co-workers6 3 from the Lederle Laboratories have described a useful procedure for the synthesis of dl-1 l-deoxy-3-thiaprostanoids based upon the conjugate addition of E-l-alkenyl ligands from lithium E-l-alkenyltrialkyl-alanate reagent 3 to the sulfur containing cyclopentenone (2)64 ... 

Vinyl aluminium compounds also carry out conjugate additions and illustrate well the difference in reactivity between vinyl alanes and the related ate complexes. If the enone can adopt the s-cis conformation, as in 175, a cyclic mechanism is possible in which aluminium both acts as a Lewis acid and delivers the vinyl nucleophile. Notice that the Zs-vinyl alane leads to the -y,8-unsaturated ketone 178 as this is again an SE2 reaction at the vinyl carbon.32... 

If the enone cannot adopt the s-cis conformation, it is necessary to convert the vinyl alane into an ate complex 179 before conjugate addition. Conjugate addition now occurs to s-trans enones, such as cyclic enones, to give the Zs-yS-unsaturated ketone 180 after aqueous work-up. Notice that this time the most stable anion is transferred - the choice is between Me, t-Bu, or vinyl. Aluminium is not a transition metal and simply releases the most stable anion as there must be some negative charge on the group being transferred. 

We have already seen examples of cuprates being used in stereochemically controlled conjugate additions to cyclopentenones and similar results can be achieved with ate complexes of vinyl alanes prepared by hydroalumination of alkynes to give e.g. 179 R = hexyl and hence the anti-A-product43 182. 

The organometallic derivatives required for the introduction of a 15-deoxy p-chain, not otherwise oxygenated, were obtained most conveniently by hydroalumination of a terminal acetylene with diisobutylaluminum hydride and conversion in situ to the lithio alanate 1 required for conjugate addition. In the absence of other oxy functions in the p-chain this process produces 15-deoxyprostaglandins such as 1 and IM conveniently and in excellent yield, as high as 80-90% for the 11,15-bisdeoxy series (Scheme 18) (25,54). 

A catalyst prepared from [Ni(acac)2] and di-isobutylaluminium hydride catalyses the conjugate addition of alkenylzirconium complexes to a,/8-enones the same catalyst also promotes 1,4-addition of alanes to cyclic a,j8-unsaturated enones. ... 

Reductions of alkyl pyridones with lithium aluminum hydride or alane are very complex and their results depend on the position of the substituents and on the reducing reagent. Since the pyridones can be viewed as doubly unsaturated lactams with a,/J- and )i, -conjugated double bonds, the products result from all possible additions of hydride ion 1,2,1,4 or 1,6. Consequently the products of reduction are alkylpiperidines and alkylpiperideines with double bonds in 3,4 or 4,5 positions [449, 7755]. 

The 1,4-addition of acetylenic alanes to conjugated enone systems proceeds through a cyclic transition state and is therefore limited to enones which are able to achieve a cw-conformation, transoid olefins giving the 1,2-adduct. 

---