Electrophiles allylation/crotylation reactions

In general, electrophilic reactions of p-hydroxyalkyl-, vinyl-, allyl-, crotyl-, homo-allyl- and dienylsilanes proceed with control of the stereochemistry of the olefinic systems formed, which is a great advantage for the synthesis of precursors of natural products such as pheromones and vitamins. 

The additions of allyl-, crotyl-, and prenylborane or -boronate reagents to aldehydes are among the most widely studied, well developed, and powerful reactions in stereoselective synthesis. The additions not only display excellent levels of absolute induction in enantioselective synthesis, but also exhibit superb levels of reagent control in diastereoselective additions. The additions of ( )- or (Z)-crotyl pinacol boronates to aldehydes have been observed to give predominantly 1,2-anti- and 1,2-syn-substituted products, respectively (Scheme 5.3) [31, 50]. The inherent stereospecificity of the reaction is consistent with a closed, cyclic Zimmerman-Traxler transition state structure [51], In the accepted model, coordination of the aldehyde to the allylation reagent results in synergistic activation of both the electrophile and the nucleophile... 

The Pd-catalyzed reaction of organometals with propargylic electrophiles proceeds readily, but the predominant products are allenes [23,98-102]. Crotyl and other 1,2-disubstituted alkene-containing allyl electrophiles also undergo Pd-catalyzed allylation with partial allylic rearrangement, which is usually accompanied by E-Z isomerization of the allyl group to a minor extent [96]. 

Crotyl silanes offer the possibility of diastereoselectivity in reactions with aldehydes in the same way as the corresponding boranes. The mechanism is completely different because crotyl trialkylsilanes react via an open transition state as the silicon is not Lewis acidic enough to bind the carbonyl oxygen of the electrophile. Instead, the aldehyde has to be activated by an additional Lewis acid or by conversion into a reactive oxonium ion by one of the methods described above. The stereoelectronic demands of the allylic silane system contribute to the success of this transformation. Addition takes place in an Se2 sense so that the electrophile is attached to the remote carbon on the opposite side of the n system to that originally occupied by silicon and the newly formed double bond is trans to minimize allylic strain. 

The reaction of allylic organometallics with electrophilic reagents is a very important tool for the formation of carbon-carbon bonds in acyclic systems and for controlling their stereochemistry. Crotyl organometallic (2-butenylmetal) species undergo a 1,3-shift of the metal at room temperature. For the stereocontrolled use of allylmetals in synthesis, it is important to avoid their equilibration. 

Examples of imine allylation in aqueous media are rafher limited compared with the carbonyl version. This is ascribed to the lower electrophilicity of the C=N function and its ease of hydrolysis to carbonyl compounds. To overcome undesired side reactions, sulfonimines are used in place of simple imines for the allylation under aqueous conditions (Scheme 8.36) [54]. Crotylation of a-sulfoirnirio esters gives the syn adducts as high as 19 1 in FD.O/THF (1 1) (Tab. 8.7) [54 c]. 

Several factors must be considered in selecting a crotyl metal or allyl metal reagent for use in an acyclic stereoselective synthesis. First, it is necessary that the new stereocenters generated in concert with the new C—C bond (Scheme 1) be formed with a high degree of stereoselectivity. This is the problem of simple diastereoselectivity. Two diastereomeric products may be produced, and in this chapter Masa-mune s synlanti nomenclature system will be used to describe them. Second, the issue of diastereofacial selectivity is encountered if the aldehyde (or other C=X reaction partner) is chiral. This is a problem of relative diastereoselectivity, and four products may be produced in the reactions of the crotyl oiganome-tallics (Scheme 2). The diastereofacial selectivity issue is also critical in the reactions of allyl metal reagents and chiral C=X electrophiles. 

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