Phosphate allylic displacement

Allylic phosphates are displaced, showing y-selectivity with respect to allylic Grignard reagents. ... 

The hydrosilation reaction is highly compatible with a number of functional groups including ether, epoxide, acetal, ketone, ester, nitrile, amine, amide, nitro, carbamate, isocyanate, phosphate, sulfide, sulfone, and others. As a consequence, it is a very attractive reaction for the construction of complex organic molecules. Sometimes allylic displacement is observed as a side reaction, especially in the reaction of allyl halides. 

Various new methods for achieving allylic substitution have emerged this year. It is interesting to note that allylic phosphates may be subjected to allylic displacement with nucleophiles in the presence of [PdCPhgP) ]. Moreover, the allylic function may be selectively displaced in the presence of an allylic acetate hence sequential alkylations/aminations are possible. Two reports have also discussed the use of allylic nitro-compounds in similar reactions. As the nitro-starting materials for these reactions are available by a variety of methods, the procedure further extends the use of 7r-allylpalladium complexes in organic synthesis. 

The remarkable regioselectivity in this transformation is attributed to inherent stereoelectronic effects of the C4-C5 olefin and P-O bond of the corresponding aUylic phosphate. For addition into the C5 position (path A, Figure 4.2, X-ray of structure 26), orthogonal ahgnment of the tt orbital of the C=C bond and a orbital of the P-O provide proper electronics for the allylic displacement to occur. However, in a potential C4 addition (path B, Figure 4.2), Sn2 addition does not take place due to coplanar ahgnment of the aforementioned tt orbital of the C=C bond to the P-O a orbital [4a]. 

Allylic stannanes can be prepared from allylic halides and sulfonates by displacement with or LiSnMe3 or LiSnBu3.146 They can also be prepared by Pd-catalyzed substitution of allylic acetates and phosphates using (C2H5)2AlSn... 

Scheme 16 Synthesis of the allylic silane 89 by an 5 2 displacement of an allylic phosphate...

Allylic compounds containing other leaving groups are also reactive toward substitution. Thus alkoxycarbonylation of allylic phosphates is a method of homologation, on which an interesting /3-lactam synthesis is based. Using PhjSiOH as nucleophile in the displacement, 2,4-hexadiene-l,6-diols are synthesizedfrom buta-dienyloxiranes. Desilylation of the products is achieved with KF. 

Similar stabilization can be effected with strongly nucleophilic but weakly basic additives. For example, amines, even highly hindered amines, are too basic to permit displacement of allylic halogen in the absence of E2-type dehydrohalogenation [17-19]. Trialkyl/aiyl phosphates, on the other hand, have shown some utility as stabilizers in these polymers. 

In another example, Pd2(dba)3 was used in conjunction with allyl diethyl phosphate, an unusual stoichiometric hydrogen acceptor in the oxidation of simple alcohols. Oxidative addition of Pd(0) into the allylic phosphate (generating a r-allyl-Pd(II) complex), is followed by an alcohol/phosphate displacement and subsequent /3-hydride elimination giving the oxidized alcohol... 

Ravn MM, Jin Q, Coates RM. Synthesis of allylic isoprenoid diphosphates by Sfj2 displacement of diethyl phosphate. Eur. J. Org. Chem. 2000 1401-1410. 

Hoveyda is one of the pioneers in the use of combinatorial chemistry techniques to discover novel ligands for catalytic asymmetric processes. A brilliant illustration is the identification of small oligopeptides as ligands for Cu-catalyzed Sn2 displacement reactions (Scheme 14.17) [95, 96). The copper complexes prepare from Schiff base-derived dipeptides such as 100 catalyze asymmetric displacement reactions of a wide range of allylic phosphates. Significantly, the method can also be utilized to prepare alkenes incorporating quaternary allylic stereogenic centers (cf 101). This approach was ele-... 

Each subunit was constructed by a phosphate-mediated desymmetrization of 24, followed by the aforementioned CM and allylic phosphate displacements. The C1-C14 subunit was envisioned to have the C1-C6 side chain appended via CM to yield advanced intermediate 40 from R,R,Ps)-26. Subsequent regioselective hydrogenation of the C5 - C6 olefin and regioselective Pd(0) -mediated allylic hydride addition (to CIO) would afford a terminal olefin armed for oxidation and subsequent installation of the Cll carbinol center (Scheme 4.15) [7a]. The C15-C30 subunit largely depended on the CM/cuprate approach (Scheme 4.13) and the advanced intermediate 41 would be synthesized from (S,S,Pr)-26 [7bj. 

Introducing Pd(0) to phosphate 44 gave rise to jr-allyl complex 44a (Scheme 4.17). The Pd(0)-mediated allylic hydride addition [26] to phosphate 44 gave the desired regioselectivity of hydride addition at the internal position (CIO) of 44a (regiose-lectivity C10/C12 = 37 1), similar to the previous cuprate additions to 26. Both examples are illustrative of the preference in regioselectivity of allyhc phosphate displacements with the endocyclic n bond. 

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