Aldehyde Lewis acid-promoted addition

Our group has exploited 4-phenylthio-l,3-dioxanes as convenient precursors to 4-lithio-l,3-dioxanes [45,65-69]. 4-Phenylthio-l,3-dioxanes 184 were originally prepared from -silyloxy aldehydes 183 [65] (Eq. 28). Lewis acid-promoted addition of phenylthiotrimethylsilane gave an unstable thioacetal intermediate, which could be converted in situ to the corresponding 1,3-dioxane. Yields for this process are variable, as the product is unstable under the conditions of its formation. The reaction slowly evolves to a mixture of the desired product, the phenylthio acetal of 183, the phenylthio acetal of acetone, and a variety of other unidentified products. 

Table 7. Stereoselectivity in Lewis-acid promoted additions of allyl tributyltin to an a-oxygenated aldehyde.

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.

Compared with aldehydes and ketones, aldimines and ketimines are less reactive towards nucleophilic addition. Furthermore, imine additions are subject to steric constraints, and rapid deprotonation proceeds with imines bearing ot-hydrogen atoms. The Lewis acid promoted addition methodology has provided a solution to these problems. 

Chiral allylic silanes and chiral aldehydes. This combination of agents provides fascinating opportunities for double asymmetric induction and allows the magnitude of the various controlling features to be expressed. The sense and level of 1,2-asymmetric induction in the Lewis acid-promoted addition of chiral E-2-butenylsilanes to chiral a-alkoxy aldehydes has been examined as well (Scheme 10-18) [37j. 

The Lewis acid-promoted addition of allylic trialkylstannanes to achiral aldehydes has been demonstrated to provide syn homoallylic alcohols in high yield [71 a,b]. The relative stereochemical outcome of the reaction of simple aldehydes with 2-butenylstannanes is discussed earlier in this Chapter. Studies on the addition of al-... 

The Lewis acid-promoted addition of allyltributylstannane and ( )-85 to /i-alk-oxy aldehydes has also been investigated [84c]. The Lewis acid-promoted reaction of a 9-siloxy aldehyde 106 with ( )-85 affords almost entirely the syn homo-... 

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). 

In a related example, Hegedus has incorporated chirality into the functionalization of the allenylstannane. Lewis acid-promoted additions of stannylallenamide 359 to simple aldehydes and imines are high i yn-selective processes (Scheme 5.2.76)." The reaction is presumed to occur via antiperiplanar 362, illustrating the anti-SE characteristics of stannyl substitution with a minimization of non-bonding interactions. 

A mild, efFident, Lewis acid-promoted addition of C3-substituted l,3-bis(silyl)propenes to aldehydes provides the corresponding 2,3,4, 5-tetrasubstituted tetrahydrofurans in excellent stereoselectivity (13TL3916). 

The lithium enolate derived from ethyl dithiane carboxylate reacts with aldehydes to furnish /3-hydroxy-ester derivatives in good yield. The Lewis acid-promoted additions of carbonyl compounds to donor-acceptor-substituted cyclopropanes, leads initially to /3-hydroxy-esters, which undergo subsequent conversion to chlorides or dihydrofurans (Scheme 41). "... 

Mechanistic Aspects - Lewis Acid-Promoted Addition of Allylsilanes and Allylstannanes to Aldehydes... 

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. 

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