Transition Lewis-acid promoted additions

Figure 2. Transition-state arrangements for Lewis acid-promoted additions of crotyl tributyltin to a-alkoxy aldehydes. The enantiomeric aldehydes are depicted for each set of additions to aid visualization.

In all examples examined the syn adduct was strongly favored. It should be noted that the thermal reaction affords the syn adduct which must be formed via a synclinal arrangement because of the cyclic nature of the transition state. Two arguments were advanced to explain the preference for a synclinal transition state in Lewis acid-promoted additions. The first of these entailed Coulombic attractive forces between the developing positive charge at the /3-position of the allylic stannane and the electron-... 

The Lewis acid-promoted addition of ) -alkoxyallylstannanes to achiral aldehydes was shown to proceed in high diastereoselectivity by an anti Se pathway (Scheme 10-64) [102]. An acyclic antiperiplanar transition structure (very similar to that shown in Fig. 10-3) was proposed to rationalize the stereoselectivity. When enantiomerically enriched allylstannanes are employed, the reaction proceeds in high enantio- and diastereoselectivity to give the homoallylic alcohols [102b]. The stereochemical outcome of the reaction is consistent with an anti Se pathway. 

A brief description of the mechanistic rationale for thermal reactions of aldehydes and allyfic stannanes is distinguished from Lewis acid-promoted additions by the supposition of closed cyclic transition states.i" The Lewis acidity of tin provides for pre-organization and the E- or Z-geometry of the starting allyfic stannane is reflected in the formation of anti- and iy -afiylation products 26 and 29 (Scheme 5.2.5). 

Summary of the Relationship between Diastereoselectivity and the Transition Structure. In this section we considered simple diastereoselection in aldol reactions of ketone enolates. Numerous observations on the reactions of enolates of ketones and related compounds are consistent with the general concept of a chairlike TS.35 These reactions show a consistent E - anti Z - syn relationship. Noncyclic TSs have more variable diastereoselectivity. The prediction or interpretation of the specific ratio of syn and anti product from any given reaction requires assessment of several variables (1) What is the stereochemical composition of the enolate (2) Does the Lewis acid promote tight coordination with both the carbonyl and enolate oxygen atoms and thereby favor a cyclic TS (3) Does the TS have a chairlike conformation (4) Are there additional Lewis base coordination sites in either reactant that can lead to reaction through a chelated TS Another factor comes into play if either the aldehyde or the enolate, or both, are chiral. In that case, facial selectivity becomes an issue and this is considered in Section 2.1.5. 

Cyclization to a morpholinolactone (59) occurs in the hydrolysis reaction of the di-A-hydroxylethylated compound (60). Compound (59) is rapidly hydrolysed by water to (61) but in file presence of equimolar amounts of amines (RNH2) or ammo acid derivatives (62) forms.56 A novel reaction of cyclic 2-diazo-l,3-dicarbonyl compounds (63) with lactones (64) affords the products (65) in the presence of rhodium acetate, Rh2(OAc)4.57 Lewis acid-promoted intramolecular additions of allylsilanes to lilac tones gave substituted cyclopentanes.58 A proposed transition state guided efforts to improve the stereoselectivity of the reaction. The reaction of a series of /1-lactone derivatives, such as (66)-(68), has been studied and they have been ling cleaved the reaction outcome is both Lewis acid and structure dependent.59... 

The first Lewis acid-promoted intramolecular addition reaction was conducted as part of a study designed to ascertain the transition-state geometry of allylic stannane additions to aldehydes (Table 45) [77]. 

The transmetallation or the metal-metal exchange reaction of an allylic tin species with an electrophile was first observed in 1970 [77]. The possibility that transmetallation may play a role in the Lewis acid-promoted reaction of allylstannanes with aldehydes was initially discussed by Tagliavini [78], Keck [79], Yamamoto [71b, 80], and Maruyama [81]. It is believed that upon transmetallation with either SnCU or TiCl4, the addition of an allylstannane and aldehyde will occur via a cyclic, six-membered transition structure. The reaction occurs by coordination of the aldehyde carbonyl with the Lewis acidic trichlorotin or trichlorotitanium reagent, thus affording the anti homoallylic alcohol (Scheme 10-42). 

As described in the sections above, it is well established that reactions of Lewis acid-activated aldehydes and ketones with silyl enolates afford -hydroxy or /7-sil-oxy carbonyl compounds (Mukaiyama aldol reactions). Occasionally, however, ene-type adducts, that is /-siloxy homoallyl alcohols, are the main products. The first example of the carbonyl-ene reaction of silyl enolates was reported by Snider et al. in 1983 [176]. They found that the formaldehyde-MesAl complex reacted smoothly with ketone TMS enolates to give y-trimethylsiloxy homoallyl alcohols in good yield. Yamamoto et al. reported a similar reaction of formaldehyde complexed with methylaluminum bis(2,6-diphenylphenoxide) [177]. After these early reports, Kuwajima et al. have demonstrated that the aluminum Lewis acid-promoted system is valuable for the ene reactions of several aldehydes [178] and for-maldimine [179] with silyl enolates bearing a bulky silyl group. A stepwise mechanism including nucleophihc addition via an acyclic transition structure has been proposed for the Lewis acid-promoted ene reactions. 

Sato determined that the use of Lewis acid was advantageous for tandem radical addition/reduction reactions in terms of both yield and selectivity [25]. As shown in Scheme 8, Lewis acid promoted the addition of the butyl radical to the a,fi-unsaturated ester, which in turn led to the formation of chelated transition state N. The improved selectivity was likely the result of a tighter complexation between the hydroxyl and carbonyl functions of the substrate and the aluminum atom. Nagano and collaborators used the same strategy with y-methoxy-a-methylenecarboxylic esters [26]. The use of La(fod)3 delivered a very good ratio of anti isomer in that reaction involving 1,3-asymmetric induction and a 7-membered cyclic transition state, illustrated by O in Scheme 8. 

Lewis acids catalyse the addition of allylic organostannanes or organosilanes to aldehydes. In contrast to the thermal reactions of allylboranes or allylstannanes, the use of a Lewis acid promotes reaction via an acyclic transition state. With a y-substituted allylsilane, such as crotyltrimethylsilane 156, the E-isomer reacts with excellent selectivity for the syn product (1.149). The corresponding Z-isomer (of 156) also favours the syn product, although with reduced selectivity (64 36). The transition state is thought to involve the ahgnment of the two tt-bonds 180° to one another (1.150). 

Often the rates and selectivities of catalytic reactions are enhanced by additional reaction components that are added in small amoimts. These added materials are often called promoters or co-catalysts. Protic acids or Lewis acids are common promoters. As is presented in Chapter 16, triarylboranes are Lewis acid promoters in hydrocyanations catalyzed by transition metal complexes. 

Compared with aldehyde, the corresponding aldimine is less reactive toward nucleophilic addition however, aldimine is able to coordinate to transition metals more strongly. This latter property of aldimine may be more important than the former in the present reaction, and the allylation of aldimine proceeds much easier than the aUylation of aldehyde. In order to achieve the Lewis acid promoted allylation of aldehydes and aldimines with allylstannane, an excess amount of Lewis acid (>2 equiv) is required. Under such conditions, both aldehyde and aldimine may be equally activated toward allylation, and the allylation of aldehyde takes place selectively. 

Consideration of the mechanism of the catalytic effect of rare earth ions on addition of organometallics to a, 8-unsaturated compounds has included addition of allyl-tributyltin to benzaldehyde catalysed by Sc. Stereospecificity in the Lewis acid-promoted allylation reaction of 3,3-disubstituted allyltins towards aldehydes has been attributed to an acyclic jyn-synclinal transition state. ... 

The additions of chiral nonracemic allenylmetal reagents to chiral a-methyl propanal derivatives have been proven useful for the assembly of polypropionate fragments. These reagents rely on allene chirality to favor one of the two possible diastereomeric transition states in the addition and, thus, differ in a fundamental way from the aforementioned methods in which a chiral auxiliary or catalyst provides the control element. For example, a chiral allenylstannane 246 is added to a chiral aldehyde (S)-230, derived from the Roche ester, in the presence of various Lewis acid promoters to afford any of the four diastereo-mers with excellent diastereo- and enantioselectivity, depending on the reaction conditions. Representative results are depicted in Scheme 10.48. From the stereocontrol point of view, these transformations follow Cram-fike open transition state models without or with chelation, respectively. If InBr3, SnCLi, BuaSnCl, or other additives... 

Ferrocen-l,l -diylbismetallacycles are conceptually attractive for the development of bimetal-catalyzed processes for one particular reason the distance between the reactive centers in a coordinated electrophile and a coordinated nucleophile is self-adjustable for specific tasks, because the activation energy for Cp ligand rotation is very low. In 2008, Peters and Jautze reported the application of the bis-palladacycle complex 56a to the enantioselective conjugate addition of a-cyanoacetates to enones (Fig. 31) [74—76] based on the idea that a soft bimetallic complex capable of simultaneously activating both Michael donor and acceptor would not only lead to superior catalytic activity, but also to an enhanced level of stereocontrol due to a highly organized transition state [77]. An a-cyanoacetate should be activated by enolization promoted by coordination of the nitrile moiety to one Pd(II)-center, while the enone should be activated as an electrophile by coordination of the olefinic double bond to the carbophilic Lewis acid [78],... 

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