Homoallylic tosylates

The displacement of homoallylic tosylates follows an entirely different course with a strong tendency for the formation of cyclo steroids. Thus, when the 3/ -tosylate of a A -steroid (187) is treated with lithium aluminum deuteride, the product consists mainly of a 3l3-di-A -steroid (188) and a 6c-dj-3,5a-cyclo steroid (189). The incorporation of deuterium at the 3 -position in (188) indicates that this reaction proceeds via a 3,5-cyclo cholesteryl cation instead of the usual S, 2 type displacement sequence. This is further substantiated by the formation of the cyclo steroid (189) in which the deuterium at C-6 is probably in the p configuration. ... 

Another example of homoallylic tosylate displacement is the lithium... 

Leaving the (retro-)aldol addition-initiated threefold anionic domino processes, we are now describing sequences which are initiated by a SN-type transformation. In particular, domino reactions based on SN/1,4-Brook rearrangement/SN reactions are well known. For example, the group of Schaumann obtained functionalized cyclopentanols of type 2-461 by addition of lithiated silyldithioacetals 2-458 to epoxy-homoallyl tosylates 2-459 in 41-75% yield (Scheme 2.106) [248]. 

A series of thiolo isomers of isoprenoid thiodiphosphate esters (45) was synthesized by treating homoallylic tosylates (46) and allylic bromides (47), with tris (tetra-n-butylamonium) thiopyrophosphates (51) (Scheme 9). The synthesis of thiopyrophosphate (51) involves selective monodemethylation of trimethyl phosphite (48) followed by condensation of the resulting phosphate (49) with thiophosphorochloridate and dealkylation of the obtained tetramethyl thiopyrophosphate (50) (Scheme 10). ... 

Deamination of cyclopropylmethylamine or cyclobutylamine in an aqueous medium results in the formation of essentially the same ratio of products (Figure 55). These products are formed also from the solvolysis of homoallyl tosylate in a weakly nucleophilic medium such as 98 % formic acid. It is tempting, then, to speculate that there could be a common mechanism linking the solvolyses of all three classes of substrate ... 

Solvolysis of homoallylic tosylates with cyclopropylcarbinyl participation has also been reported. ... 

Certain homoallylic tosylates react with KOAc to provide the corresponding acetylated cyclopropane derivatives and/or the expected homoallylic acetates (eq 10). Formation of the cyclopropane derivative is suggested to occur via neighboring group participation of the alkene, and is subject to steric and conformational constraints of the substrate. 

Cyclobntanes.— Although [2 -i- 2]cycloadditions are the commonest routes to cyclobutanes, other methods are also used. The homoallylic tosylates (121) may be made by Knoevenagel condensation and give the oxygenated cyclo-butylcarbonitriles (122) with alkoxides. With borohydride reduction, the... 

In support of a radical pathway for such reactions, both cyclopropylcarbinyl bromide and iodide gave rise to appreciable homoallylic substitution product with the foregoing metallostannanes. In contrast, the corresponding chloride and tosylate gave only the unrearranged product. 

Ytterbium triflate [Yb(OTf)3] combined with TMSG1 or TMSOTf are excellent reagents for the conversion of a-methyl styrene and tosyl-imines into homoallylic amides 32 (Equation (19)) (TMS = trimethylsilyl).29 These conditions produce the first examples of intermolecular imino-ene reactions with less reactive imines. Typically, glyoxalate imines are necessary. A comprehensive examination of the lanthanoid metal triflates was done and the activity was shown to directly correlate with the oxophilicity scale. The first report used preformed imines, and subsequently it was found that a three-component coupling reaction could be effected, bypassing the isolation of the intermediate imine.30 Particularly noteworthy was the successful participation of aliphatic aldehydes to yield homoallylic amines. 

With the appropriate precursor rac-35 in hand, the rearrangement key step was examined. As expected, basic treatment of y-keto-tosylate rac-35 resulted in the formation of a 56/44 mixture of the formal substitution product rac-43 and rac-44 as the product of homoallylic rearrangement (Scheme 12), in a combined yield of 95%. 

The 2-aryl substituted cyclopropylcarbinyl cations have partial homoallylic character, whose contribution to the resonance hybrid increases when strong electron-withdrawing substituents (e.g. phenyl) are attached at the C2. Thus, 3-arylcyclobutyl tosylates on acetolysis give the homoallylic acetates predominantly, through the intermediate formation of the 2-arylcyclopropylcarbinyl cations (equation 21). 

The resulting homoallylic alcohol 24 is next transformed into a tosylate, which subsequently undergoes nucleophilic substitution with sodium iodide in a Finkelstein reaction to give compound 13. 

Corey s asymmetric allylation methodology was utilized in the total synthesis of amphidinolide T3 (95), a marine natural product that exhibits significant antitumor properties37 (Scheme 3.1gg). The asymmetric allylation of the aldehyde 96 was carried out successfully with chiral allylborane reagent generated in situ from allyltributylstannane and (R,R)-82 to furnish the homoallylic alcohol desired (97) in 85% yield with excellent diastereoselectivity. Subsequent conversion of the alcohol to the tosylate ester followed by treatment with potassium hydroxide resulted in formation of the trisubstituted tetrahydrofuran 98. 

Inspection of models shows that the departure of a 3 a-tosylate anion cannot derive assistance from rear attack by the sr-electrons with ring A in its stable chair conformation (12). The alternative conformation (13) which might permit homoallylic participation [34] is highly strained and cannot compete with elimination of the m is-axial 4j8 proton to give cholesta-3,5-diene (14), the major reaction product (see p. 252 for further discussion). 

Support for the intermediacy of a homoallylic cholecalciferyl cation (381) in the formation of the 3,5-cyclo-products (375) and (376) came from the solvolysis of cholecalciferyl tosylate (374) under a variety of conditions. Depending upon the solvent, and any nucleophiles supplied, products showed compositions varying from total retention of configuration to 89% inversion, interpreted as evidence of competing pathways through either the homoallylic cation (381) or an 5n2 substitution, respectively. 

Ion pair return to positions more remote than the adjacent carbon is quite common with homoallyl-cyclopropylcarbinyl cations, cf. compounds (92)-(94)l05 lol Even the vinyl tosylate (96) is produced from either of the allenic isomers (95) and (97)108 In contrast, 5-norbornen-2-yl brosylate (98) does not yield any nortricyclyl brosylate (99) although scrambling of a deuterium label, (98a) (98b), is ca. 12 times faster than solvolysis109. ... 

Homoallylic participation was first invoked by Shoppee to account for the high rates and the stereospecificity of 3/3-(415) and i-cholesteryl (416) interconversions339). The double bond in (415) is clearly restricted to participation by one end. We cannot distinguish, however, between a homoallylic and a cyclopropylcarbinyl cation as the intermediate [cf. (387) and (355)] because both would be chiral. The same limitations apply to the 3-cyclohexenyl system. The tosylate (417) acetolyzes slightly more slowly than cyclohexyl tosylate340). The products include the acetate (418) corresponding to the starting material, the bicyclic acetate (419), and (420) as a result of hydro-... 

The 5-norbomen-2-yl system (421) is relatively well understood. Homoallylic participation is weak so that the double bond actually causes a rate retardation342-. Participation is not detected by the tool of increasing electron demand (Section 7.2.2.)244,266. Yet the exo-tosylate (421), X=OTs, acetolyzes 7000 times faster than the mfo-tosylate (425), X=OTs, to give the tricyclic acetate (424) as the principal product (ca. 90%)343. The hypothetical homoallylic intermediate (422) is... 

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