Allyl compounds nucleophilic displacement

Three selective methods to remove protective groups are receiving much attention assisted, electrolytic, and photolytic removal. Four examples illustrate assisted removal of a protective group. A stable allyl group can be converted to a labile vinyl ether group (eq. 4) a /3-haloethoxy (eq. 5) or a /3-silylethoxy (eq. 6) derivative is cleaved by attack at the /3-substituent and a stable o-nitro-phenyl derivative can be reduced to the o-amino compound, which undergoes cleavage by nucleophilic displacement (eq. 7) ° ... 

Bordwell and Cooper211 drew attention to the inertness of a-halosulfones and related compounds towards nucleophilic displacements of the halogen. Thus chloromethyl p-tolyl sulfone reacts with potassium iodide in acetone at less than one-fiftieth of the rate for n-butyl chloride. On the other hand, l-(p-toluenesulfonyl)-3-chloro-l-propene reacts about 14 times faster than allyl chloride. This contrast (and other comparisons) led the authors to attribute the inertness of a-halosulfones to steric hindrance, which was eliminated when the sulfonyl group was more remote from the reaction center. 

A very mild method that is useful for compounds that are prone to allylic rearrangement involves prior conversion of the alcohol to the tosylate, followed by nucleophilic displacement with halide ion. 

Acid-induced mcemization and isomerization of chiral allylic alcohols. Bimolecular nucleophilic displacements in allylic compounds are known to proceed via the four possible pathways shown in Scheme 19. 

Magid, R. M. Nucleophilic and organometallic displacement reactions of allylic compounds stereo- and regiochemistry. Tetrahedron 1980, 36, 1901-1930. 

The first step in the hydrolysis in tert-butyl alcohol is probably nucleophilic displacement of fluorine in the reactive allylic position. Spontaneous elimination of hydrogen fluoride from the geminal fluorohydroxy compound yields perfluorocyclopent-2-en-l-one. 

Nucleophilic displacement of fluorine atoms in the reactive allylic position affords an enol of a fluorinated 1,3-diketone, 2H-pentafluoro-cyclopentane-l,3-dione (compound H) [57]. ... 

Palladium-catalyzed heteroannulation is illustrated by synthesis of substituted l//-benzo[rf]azonine 227, which was prepared from allene and tosylamide-containing aryl halide (Equation 26). The reaction was suggested to proceed by addition of an arylpalladium compound to the allene to generate a 7i-allylpalladium intermediate, which subsequently undergoes nucleophilic displacement of palladium at the less-hindered end of the 7i-allyl system <1998JOC6859>. 

An efficient method for the preparation of mono-heterocyclic compounds such as substituted tetrahydrofurans with high stereoselectivity via intramolecular SN2 O-cyclization of alkoxides has been reported. This is a nucleophilic displacement with a simultaneous allylic rearrangement (Scheme 321).1114... 

Allylic compounds containing other le stitution. Thus alkoxycarbonylation of all tion, on which an interesting )3-lactam nucleophile in the displacement, 2.4-he ac dienyloxiranes. Desilylation of the produc Either the 3 2 or the 3 2 pathway for propane" can be selected by using. V-nucI... 

Acetates of MBH adducts have also been established for the synthesis of sulfur-containing trisubstituted alkenes via a nucleophilic displacement protocol, in either S- 2 or S- 2 fashion with 5-centered nucleophiles, such as thio-lates, ° arenesulfinate and thiocyanate anions. Significantly, these reactions are highly stereoselective for both acrylonitrile/acrylate ester-derived MBH acetates, but with a reversed stereochemical directive effect, that is, acrylonitrile-derived MBH acetates afford ( )-sulfur-containing trisubstituted alkenes 336 as the sole product, while acrylate ester-derived MBH acetates afford (Z)-olefins 335 exclusively under the same reaction conditions. Both (Z)-and ( )-allyl sulfides have been stereoselectively obtained from MBH acetates in a one-pot with treatment with benzenethiol in the presence of catalytic amounts of 15% aqueous NaOH and TBAI in DM SO at room temperature (Scheme 3.146). ° The method has also been applied for the synthesis of (Z)-3-(4-methoxybenzylidene)thiochroman-4-one (337), a potent antifungal compound (Scheme 3.147). 

The Pd-catalysed allylation of carbon nucleophiles with allylic compounds via Jt-aUylpaUadium complexes is called the Tsuji-Trost reaction [32]. Typically, an allyl acetate or carbonate (54) reacts with a Pd-catalyst resulting in displacement of the leaving group to generate a Jt-allylpalladium complex (55) that can undergo substitution by a nucleophile (56) (Scheme 4.14). In 1965, Tsuji reported the reaction of ti-aUylpaUadium chloride with nucleophiles such as enamines and anions of diethyl malonate and ethyl acetoacetate. A catalytic variant was soon reported thereafter in the synthesis of allylic amines [33]. In 1973, Trost described the alkylation of alkyl-substituted 7i-aUylpalladium complexes with methyl methylsulfonylacetate... 

Nitrogen compounds serve as reactive nucleophiles toward rr-allylpalladium complexes (Scheme 1). Diethylamine is allylated with allyl alcohol.Allylic chlorides react with amines without a Pd catalyst, but the reaction is accelerated with such a catalyst. For example, in the Pd-catalyzed reaction of l-acetoxy-4-chloro-2-butene with diethyl amine at 25 °C, only the allylic chloride is displaced without attacking the allylic acetatoxy moiety. The uncatalyzed reaction proceeds at 80 The secondary amine is obtained without... 

Enol ethers with potential leaving groups at the allylic position (e. g. compounds of general structure 3) can be subject to acid-catalyzed additions or nucleophilic displacements, protonic acids commonly giving products (5) of the former reactions while Lewis acids favour the formation of unsaturated products (7,8)... 

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