Allylic transfer

Chain transfer to monomer is particularly favored with allylic monomers (e.g., allylic acetate) which have the structure CH2=CH-CH2X with a C-H bond alpha to the double bond described as an allylic C-H. While the propagating radical is very reactive, the radical formed by transfer to allylic C-H in the monomer is particularly stable and unreactive due to resonance stabilization [Eq. (6.125)] and does not initiate new chains. Allylic transfer is thus variously known as degradative chain transfer to monomer, autoinhibition, or allylic termination. 

Problem 6.24 Suggest a kinetic scheme to account for the following characteristics of free-radical polymerization of allylic monomers  

Combination with Rp = kp [M ] [M] and Ri = 2fkd ] leads to kpRi Ifkpkd [I] 

For degradative chain transfer, kp ktrM- Therefore Rp is very low. Equation (P6.24.2) shows that Rp is rst order in [I]. 

Since the allylic radical which is formed by the transfer reaction has high resonance stability, it is particularly unreactive and does not initiate new chains, with the result that the allylic monomer polymerizes at abnormally low rates and the degree of polymerization, which is independent of the polymerization rate, is very low (for example, only 14 for allyl acetate). These effects are the consequence of degradative chain transfer (see Table 6.8) to monomer, also known as autoinhibition. In this polymerization, the propagation and termination reactions will have the same general kinetic expression resulting in the unexpected dependence of the rate on the first power of the initiator concentration (see Problem 6.28). 

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An interesting and stereoselective synthesis of 1,3-diols has been developed which is based on Lewis acid promoted reactions of /f-(2-propenylsilyloxy (aldehydes. Using titanium(IV) chloride intramolecular allyl transfer takes place to give predominantly Ag/r-l,3-diols, whereas anti-1,3-diols, formed via an / / /-molecular process, are obtained using tin(IV) chloride or boron trifluoride diethyl ether complex71. 

Reagents of type 1 are the most important and exhibit the highest reactivity towards carbonyl compounds. The reactivity can be further tuned by altering the substitution on titanium. Reagents of type 2 show lower reactivity, but higher selectivities, but have, so far, only been used occasionally (Section 1.3.3.3.8.2.1.2.). Reagents of type 3, derived from chiral alcohols, accomplish efficient enantioselective allyl transfer (Section 1.3.3.3.8.2,3.3.). 

However, the free hydroxyaldehyde and tetra-2-propenylzirconium lead predominantly, in an intramolecular allyl transfer, to the product of formal chelation control87. 

This allyl transfer reaction, which is a valuable synthetic method, has been shown to be a free-radical chain substitution (SH2 ), namely... 

Hydroxamic acids constitute an important class of siderophores, which play a major role in iron solubilization and transport. Some of them are important as therapeutic agents. The Michael addition of nitroacetyl proline esters to allyl acrylate followed by Pd(0)-catalyzed intramolecular allyl transfer and subsequent reduction of the nitro group yields a novel class of cyclic hydroxamic acids related to pyroglutamic acid (Scheme 5.9).85... 

Based on the Kulinkovich reagent (Ti(OiPr)4/iPrMgCl), a new route to allyltita-niums has been devised by Sato and coworkers and this has allowed the synthesis of chiral allylTi reagents which, by reaction with aldehydes and imines provide diverse polyfunctional chiral building blocks. Thus, while a number of versatile and dependable Ti-based allyl-transfer reagents are now available, the development and employment of chiral allyltitaniums appears to be poised for new application. 

The allylic HYCRAM derivative was subsequently modified by insertion of a standard amino acid between the aminomethyl resin and the hydroxy butenoic acid moiety. Using this allylic anchor, the resin-linked, glycosylated HIV peptide T-derivative 164 was synthesized by application of Fmoc amino protection and sidechain protection with lert-butyl groups. The lac-tosamine peptide T (165) could be released from the resin by application of the palladium(0)-catalyzed allyl-transfer reaction to V-methyl aniline as the allyl acceptor. 

FIGURE 3.13 Cleavage of an allyl-based protector (Stevens Watanabe, 1950) by palladium-catalyzed allyl transfer to a nucleophile in the presence of a proton donor.27-28... 

Common protectors of hydroxyls are benzyl and 2-bromobenzyl for Boc chemistry and tert-butyl for Fmoc chemistry. Trityl provides a third level of selectivity for both chemistries because it can be removed by mild acid (1% CF3C02H in CH2C12), which does not affect tert-butyl based protectors. O-Allyl is not removable by palladium-catalyzed allyl transfer, so it is not appropriate. Protection by acyl such as benzyloxycarbonyl is possible, but 0 -acyl protectors can be problematic because of their tendency to shift to adjacent amino groups (see Section 6.6) and... 

Diethylamine (11) is an inexpensive base that removes fluorenylmethyl-based protectors without forming an adduct with the liberated moiety, and it can be eliminated by evaporation. It has been employed as nucleophile for palladium-catalyzed allyl-transfer reactions (see Section 3.13). 

The explanation given is that allyl transfer takes place from palladium(II) to a palladium(O) species [6], which changes the face co-ordinated to palladium See Figure 13.10. If now a chiral diphosphine is present, one of the routes for nucleophilic attack may be fester and selectively only one enantiomer may form [4],... 

Bischler-Napieralski reaction, 6, 2 Bis(chloromethyl) ether, 1, 3 19, warning Boron enolates, 51, 1 Borane reagents, for allylic transfer, 73,... 

By far the most generally useful synthetic application of allyltributyltin is in the complementary set of transition metal- and radical-mediated substitution reactions. When the halide substrates are benzylic, allylic, aromatic or acyl, transition metal catalysis is usually the method of choice for allyl transfer from tin to carbon. When the halide (or halide equivalent) substrate is aliphatic or alicyclic, radical chain conditions are appropriate, as g-hydrogen elimination is generally not a problem in these cases. 

This method can successfully be extended to /V-protected aziridines too. The reaction of aryl aziridines also proceeds smoothly with the allyl transfer occurring exclusively at the benzylic carbon to produce the corresponding y-amino olefin (Fig. 6). The versatility of the method is illustrated by various examples in Table 2. 

We have developed asymmetric syntheses of isocarbacyclin [3] (Scheme 1.3.2) and cicaprost [4] (Scheme 1.3.3) featuring a Cu-mediated allylic alkylation of an allyl sulfoximine [5-7] and a Ni-catalyzed cross-coupling reaction of a vinyl sulf-oximine [8-10], respectively, transformations that were both developed in our laboratories. The facile synthesis of an allyl sulfoximine by the addition-elimination-isomerization route aroused interest in the synthesis of sulfonimidoyl-sub-stituted aiiyititanium complexes of types 1 and 2 (Fig. 1.3.2) and their application as chiral heteroatom-substituted allyl transfer reagents [11]. 

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. 

Deoxygenation of allyttc alcohols.3 A method for conversion of allylic alcohols to l-alkenes is outlined in equation (I). The first step is an allylic rearrangement of an Oallyl xanthate to 2. The second step is an allyl transfer from sulfur to tin with tri-n-butyltin hydride to give the allylic stannane (3). The last step, destannylation, is a well-known mule to terminal alkcnes.4... 

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