Allylic displacements

Nucleophiles can be introduced at C4 of 1,2-type 64 (Scheme 15) and at C4 or C5 of 1,3-type N-alkoxyazolium salts 67 (Scheme 16) by an allylic displacement of ROH and loss of a proton. This reaction mode competes with the nucleophilic addition followed by elimination of ROH described in Section 1.5.1.3. Consequently all ring protons in 1,2-type and 1,3-type azoles become activated but predictions of product distribution turn difficult. In all cases the net result is replacement of hydrogen at the heteroaromatic nucleus with a nucleophile. The sequence can be performed in one pot. 

Both ring positions and lateral positions - both at C4 and C5 - are activated by the O-silylation. Substituents can be introduced at the lateral 5-position by O-silylation followed by abstraction of the activated lateral proton with a weak non-nucleophilic base. The neutral species 428 formed is subject to nucleophilic allylic displacement of the silyloxy anion rendering laterally substituted triazole 429 in one pot (Scheme 121). 

Fluoride-induced rearrangements of terminal to internal isomers of perfluoro-alkenes are well established [70-72], for example the rapid isomerisation of perfluoro-l-pentene to the thermodynamically more stable isomer occurs in the presence of cesium fluoride (Scheme 33) [73], Allylic displacement reactions occur readily and with a stereochemistry suggesting steric control (Scheme 34) [74],... 

The unique feature of type (95) is that the double bond is very much activated to nucleophilic attack but reactions proceed with allylic displacement of fluoride ion, often producing an intermediate that is highly reactive towards further attack by nucleophiles, including intramolecular processes. For example, the furan derivative (99) may be obtained directly from (37) (Scheme 60, and also see Scheme 66, later). Other nucleophiles give products of di- and polysubstitution [126] (Scheme 61). The bicyclobutylidine system (41a) is electronically very similar to the tetramer (37), but (41a) is particularly reactive, as a consequence of strain (Scheme 62, [111]). 

The concept of Sn2 reactions was presented in Chapter 4. In the context of this discussion, the Sn2 mechanism was extended to allylic systems. These allylic displacements, because of their mechanistic similarities to SN2 reactions, were designated SN2 reactions. A representation of an Sn2 mechanism, compared to an SN2 mechanism, is illustrated in Figure 7.2 using arrow pushing. 

The iT-face differentiation in favor of adducts (443) was more pronounced with increasing amounts of the Lewis acid and at lower reaction temperatures (cf. entries 3/4 and 8/9). The cooperative effect of chiral auxiliaries at the diene and at the dienophile units is exemplified by the double diastereoface selective addition presented in entry 2. Particularly noteworthy is the outstanding ir-face selectivity, observed in the [4 + 2) cycloaddition of juglone (445). Removal of the prosthetic group fiom adducts (443) was accomplished via hydrogenolysis or allylic displacement, as illustrated by the key step (447) (448) of a synAesis of enantiomerically emiched (+)-ibogamine (Scheme 105). ... 

In l-chloro-2-hydroperfluorocycloalkenes, a direct nucleophilic attack by hydrides substitutes hydrogen for chlorine giving (1), whereas allylic displacement (5n2 ) replaces fluorine and forms (2) (equation 6 and Table 3)7... 

Zirconocene dichloride was used as a catalyst for allylic displacement of allyl ethers with Grignard reagents [449]. An asymmetric version of this reaction by the use of a catalytic amount of a chiral zirconocene dichloride was independently reported, and it achieved a nearly complete chirality induction [Eq. (205) 450]. 

Allylic displacement. Although the most well-known catalysts are Pd(0) species, a combination of [(codlRhClJ and (PhO)jP has the same efficacy. More highly substituted products are favored. 

Allylic displacements. Ring opening of perhydro-iV-tosyl-2-allyl-l,3-oxazines with Grignard reagents leads to enamine derivatives. Temperature dependence of the double bond configuration is remarkable. Allylic carbamates furnish predominantly fZl-alkenes. ... 

Organocopper/zinc reagents. 18,262-Preparation. Alkylzinc-copper r activated Zn and then with Cu(OAck-lj Allylic displacements. 7t-Complei reaction with the organocopper/zinc rcaj of configuration. For chain extension is reacted with MeCu(CN)Li and then... 

The stereochemistry of the SN2 reaction has been shown to be variously syn (the nucleophile and leaving group are on the same face of the ally lie system) or anti, depending on the nature of the nucleophile and leaving group. For example, the cis isomer 26 with piperidine gave 27, in a clean syn allylic displacement, whereas Na+-SPr gave a ca. 2 1 mixture of isomers in which the trans isomer 28 was the major product. This trend toward anti substitution with RS- is more pronounced (almost exclusive) in the acyclic case 29. 

Scheme 4.4 details a short synthesis by Trost of an intermediate employed in the Gerlach synthesis of 9. ° Protected aldol 19 was reacted with a-lithio ethyl vinyl ether and the resulting alkoxide intermediate acylated to provide the protected diol 20 in 75% yield. Chain extension by way of a palladium-mediated allylic displacement with isopropyl phenylsulfonylacetate followed by ester exchange afforded a 62% yield of 21. Hydrolysis of the enol ether and 3-elimination of the sulfonyl group produced 22 in 66% yield. Ketalization of 22 then gave 16, which had been previously converted to the natural product in 50% yield. 1 ... 

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