Allylmetal additions

Three-Carbon Chain Elongations 13.5.6.1 Allylmetal Additions... 

The most logical organization of the mechanistic and stereochemical features of the allylmetal addition reaction is by metal. These two most important components of the reaction are inexorably bound and critically dependent on the nature of the metal. In turn, the metal also carries with it the types of ligands and activators that are often also integral to a discussion of the mechanism and moreover influential in the stereochemical outcome of the process. Thus, each subsection, defined by metal or metalloid class, will contain a discussion of the current structure of understanding of the reaction mechanism followed by the stereochemical consequences at all levels of stereoselection outlined above. 

The nucleophilic addition of unsubstituted and carbon- or hetero-substituted allylmetals to carbonyl compounds is a straightforward step in addition to the C-C bond formation, the introduction of further functionality to the molecule is achieved. 

The intention of this section is to assist the potential user to choose the optimal allylmetal reagent in carbonyl addition reactions. 

Allyl anion synthons A and C, bearing one or two electronegative hetero-substituents in the y-position are widely used for the combination of the homoenolate (or / -enolate) moiety B or D with carbonyl compounds by means of allylmetal reagents 1 or 4, since hydrolysis of the addition products 2 or 5 leads to 4-hydroxy-substituted aldehydes or ketones 3, or carboxylic acids, respectively. At present, 1-hetero-substituted allylmetal reagents of type 1, rather than 4, offer the widest opportunity for the variation of the substitution pattern and for the control of the different levels of stereoselectivity. The resulting aldehydes of type 3 (R1 = H) are easily oxidized to form carboxylic acids 6 (or their derivatives). 

Table 6. Synthons and Reagents for Carbonyl Addition to y-, at,y- and y,y-IIetero-Substituted Allylmetals...

As a result of additional 1.3-diaxial interactions, involving the C-l position of the allylmetal moiety in the chair transition state 7, a boat transition state 8 has been proposed, to provide amine 6. 

Both dienyl- and 7r-allylmetal complexes of Fe,492 Mo,493,494 and W374 have also been prepared and undergone similar reactions with oxygen nucleophiles. One pertinent example is the reaction of 7r-allylmolybdenum complexes with internal alcohols leading to THFs (Equation (128)) 493 additional examples of this chemistry have appeared in a... 

Scheme 13.1. Synthesis of homoallylic alcohols by addition of allylmetal compounds to aldehydes.

In 1998, Kubota, Nakamura and coworkers stndied the addition of substituted (alkoxy)allyllithium and zinc reagents to cyclopropenone acetaP. They found that the regioselectivity of the (alkoxy)allyllithiation is dependent on the substituent, while the diastereoselectivity remains constantly high (>97%). This is supported by their theoretical study (at the B3LYP/6-31G level. Scheme 3) which reveals that a (hydroxy)allyllithium species of 7r-allylmetal nature can react with cyclopropene via two [2 + 2]-type four-centered transition states of similar energies leading to a- and y-adducts. 

In addition to the predominant allyl and crotyl reagents, a large nnmber of allylic borane 1 and boronate derivatives 2 (Eq. 1) with varions snbstitnents (R -R" ) have been reported. Interested readers can refer to the comprehensive Tabnlar Snrvey at the end of this monograph, which covers the literatnre np to the end of 2005. Several reviews on allylic boron componnds and other allylmetal reagents and their additions to carbonyl compounds and imines have been written prior to this one," " and these sonrces may be consnlted if a more in-depth historical perspective is desired. 

Structures 1 and 1, with identical relative configuration at C-2. C-3, are not covered by Masamune s very scant directions which do not include a guideline on the definition of the backbone. Thus, an allylmetal expert , having prepared 1 as one member of a series with the substituent of the ally] group varied, will probably describe 1 as syn, but investigators working on aldol reactions or conjugate additions will certainly prefer the term anti for 1. ... 

Additionally, some Pd-catalyzed type II zinc-ene cyclizations have been described. When the allylic acetate 181 was treated with EtiZn in the presence of a catalytic amount of Pd(PPh3)4, its slow conversion to a cyclic organozinc species by a type zinc-ene reaction was observed and iodinolysis afforded the six-membered ring 182 in relatively low yield. The regioselectivity was noteworthy as C-C bond formation occurred at the most substituted terminus of the allylmetal. By contrast, the type II palladium-ene cyclization of the allylic acetate 181, in conjunction with a /1-elimination process, proceeded with opposite regioselectivity and led to the six-membered ring 183 (equation 88)114. 

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