Allylation nucleophiles

Scheme 2.24 Whole catalytic cycle of frost s Mo-7t-allyl nucleophilic reaction.

A practical method for the enantioselective addition of an allylic nucleophile to an aldehyde has been acid-mediated allyl transfer, as exemplified by the conversion of 1 and 2 to 3. While this method worked well for crotyl, allyl transfer itself suffered from eroded ee s. Teck-Peng Loh of the National University of Singapore has found (Tetrahedron Lett. 2004,45,5819) that camphorsulfonic acid (CSA) mediates this conversion without racemization. The alcohol 1 is prepared by addition of allyl Grignard to camphor, so both enantiomers are readily available. 

Asymmetric addition of functionalized allylic nucleophiles is also a useful process. Yoshito Kishi of Harvard University has shown (J. Am Chem. Soc. 2004,126. 12248) that 2,3-dibromopropene 4 will add with high enantioselectivity to linear and branched aliphatic aldehydes. The analogous Cl and I derivatives can also be prepared, using the same approach. 

Allyl esters, carbonates, and carbamates readily undergo C-O bond cleavage upon reaction with palladium(O) to yield allyl palladium(II) complexes. These complexes are electrophilic and can react with nucleophiles to form products of allylic nucleophilic substitution. Linkers based on this reaction have been designed, which are cleavable by treatment with catalytic amounts of palladium complexes [165,166], For the immobilization of carboxylic acids, support-bound allyl alcohols have proven suitable (Figure 3.12, Table 3.7). 

Table 3.7. Linkers cleavable by palladium(0)-catalyzed allylic nucleophilic substitution.

Abstraction of laterally situated protons followed by allylic nucleophilic displacement of ROH... 

The allyl silicon bond is cleaved by fluoride ion under anhydrous conditions to produce an allylic nucleophile which attacks the enone in a 1,4-manner. 

P-Menthylphosphetanes 77, in which an optical active dioxolane group is introduced at the a-position, have also provided asymmetric catalytic activity in the palladium-catalyzed allylic nucleophilic substitution of 1,3-diphenyl-propenyl acetate with the sodium salt of dimethyl malonate (Equation 12). 

California Red Scale is a worldwide citrus pest which can be controlled by means of the pheromone 60. Cohen used reductive lithiation to generate versatile allylic nucleophiles applicable to this type of target.6 The allyl sulfide 61 is lithiated by BuLi and reacts with butenyl bromide a to sulfur to yield 63. Reductive lithiation (Li, DBB) of the product yields allyllithium 64. A regioselective reaction of this nucleophile with formaldehyde at the more substituted terminus is ensured by transmetallation to the allyl titanium 65, which gives 66 after treatment with formaldehyde and bromination. 

The six-member ed transition state for the reaction of an allylic borane or boron ate is very reminiscent of the cyclic transition state for the aldol reaction you met in Chapter 34. In this case the only change is to replace the oxygen of the enolate with a carbon to make the allyl nucleophile. The transition state for the aldol reaction was a chair and the reaction was stereospecific so that the geometry of the enolate determined the stereochemistry of the product aldol. The same is true in these reactions. -Crotyl boranes (or boronates) give anti homoallylic alcohols and Z-crotyl boranes (or boronates)... 

The use of other mixed reagents to promote acylation and subsequent enolization of the ketone during its formation have been reported by Fehr. The success of the method depends on the ease of ketone deprotonation and thus was limited to substituted allylic nucleophiles. The final product was obtained entirely in the form of the a. -unsaturated ketone. A combination of the nucleophilic Grignard reagent and the nonnucleophilic base lithium diisopropylamide converts sterically hinder ester (50) into a-damas-cone (52) via (51) (Scheme 16). The ratio of ketone to tertiary alcohol was 98 2 (many cases gave selectivity greater than 9 1) however, a few examples showed a substantial amount of tertiary alcohol formation. 

The formation of chiral secondary homoallylic alcohols via the enantioselective addition of allylic nucleophiles to aldehydes is an important tool in organic synthesis. An efficient way to achieve this transformation is to use allylic organometallic reagents in the presence of chiral Lewis acid catalysts. The most widely studied catalysts in the area... 

Guthrie, R. D., Irvine, R. W. Allylic nucleophilic substitution reactions in sugars. I. Tri-O-acetylglycals and related compounds. Carbohydr. Res. 1980, 82, 207-224. 

The transmetalation process essentially leads to a new allylic nucleophile, which may exhibit very different properties compared to the starting stannane. A change in diastereofacial selectivity is often observed. For example, stannane 201 reacts with 3-methylbutanal to yield primarily the l,4syn product 202 via an internally coordinated synclinal arrangement 203 (Scheme 5.2.45). 

As part of a synthesis of sesquiterpenes, the sulfone 182 and the allylic halide 183 were coupled (allylic electrophile as well as allylic nucleophile ) to give a mixture of diastereoisomers of 184 that gave the triene 185 on elimination.48 Note that the new double bond is exclusively E. 

Allylstannanes are made by very similar methods to those used for allylsilanes, where the same problems arise when unsymmetrical allyl nucleophiles are treated with tin halides. " To solve this problem, there are tin equivalents of the reactions in Schemes 63, 69, 70, 75 - and 77. ... 

The Ni-catalyzed coupling is a superior method for the preparation of unsymmetrical 1,5-dienes, an allylic nucleophile being generated from fragmentation of a tertiary homo-allylic alcohol. ... 

In this book, a distinction is made between additions that involve allylic nucleophiles and those that do not. For the purposes of this discussion, the addition of enolates and allylic nucleophiles will be labeled 7t-transfers, and nonallylic nucleophiles will be labeled a-transfers, as illustrated in Figure 4.1. Note that for <5-transfers aggregation is possible, so that the addition may proceed through a transition state featuring either a four-membered ring or a six-membered ring. This chapter covers 1,2- and 1,4 additions to carbonyls by o-transfer the addition of enolates and allyls (7i-transfer) is detailed in Chapter 5. 

Another interesting enantioselective transformation under high pressure was reported by E. Nakamura et al. in the construction of quaternary carbon centers by allylzincation [84]. The allyl zink reagent, 185 possessing an anionic bisoxazoline (BOX) ligand was used to deliver the allyl nucleophile to the alkene 184 regio-... 

The stereochemical outcome of allylation reaction is very satisfying due to predominant creation of threo isomer. This selectivity has been interpreted on the basis of the Cram type chelation [113,114]. It consists in formation of the five membered chelate between the allyl, indium and a-OH group of aldose, followed by the attack of the allylic nucleophile at the aldehyde from the less hindered side, thus favoring the syn product [111-114], Similarly, the other sugars i.e. D-ribose, D-xylose and D-arabinose have been reacted to achieve the appropriate ulosonic acids [112]. 

The inverse temperature-dependent solubility in aqueous media of polymer-bound palladium(0)-phosphine catalysts, based on the water-soluble polymer poly(Wisopropyl)acrylamide (PNIPAM) 28, was also used to recycle and reuse these catalysts in nucleophilic allylic substitutions (Equation (8)) and cross-coupling reactions between aryl iodides and terminal alkynes (Equation (9)). The catalyst was highly active in both reactions, and it was recycled 10 times with an average yield of 93% in the allylic nucleophilic substitution by precipitation with hexane. ... 

Preparation of the temporary connection was achieved by reaction of acetoxy lactam 316 with allyl(chloro)silane 317, generating the A -silyl species 318. Exposure to TMSOTf at 0 °C effected in situ formation of the /V-acyliminium species, which was trapped by the pendant allyl nucleophile, providing two out of the possible four dia-stereoisomeric cyclized products, 319 and 320 in a 4 1 ratio (Scheme 10-102). Formation of the two products may be accounted for by cyclic T. S.s where addition occurs onto the re face of the azetinone, anti to the sterically demanding silyl ether group through a chair-like or boat-like conformation. 

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