Cyclic tetrasubstituted alkenes

It was noticed by Rickborn and Wood [4] and Field and Galagher [5] that cyclic tetrasubstituted alkenes undergo such a isomerization under much milder conditions. This approach enables highly stereoselective conversion of a variety of cyclic tetrasubstituted alkenes of type 34 into polyfunctional products of type 37 in one-pot reactions via the intermediate organoboranes 35 and 36 (Scheme 5) [6-8]. 

Scheme 5. Allylic C-H activation via hydroboration of cyclic tetrasubstituted alkenes.

S. Oishi, K. Miyamoto, A. Niida, M. Yamamoto, K. Ajito, H. Tamamura, A. Otaka, Y. Kuroda, A. Asai, N. Fujii, Application of tri- and tetrasubstituted alkene dipeptide mimetics to conformational studies of cyclic ROD peptides. Tetrahedron 62 (2006) 1416-1424. 

Epoxy alcohols. A few years ago Mihelich1 was granted a patent for preparation of epoxy alcohols by photooxygenation of alkenes in the presence of titanium or vanadium catalysts. Adam et al.2 have investigated this reaction in detail and find that Ti(IV) isopropoxide is the catalyst of choice for epoxidation of di-, tri-, and tetrasubstituted alkenes, acyclic and cyclic, to provide epoxy alcohols. When applied to allylic alcohols, the reaction can be diastereo- and enantioselective. The reaction actually proceeds in two steps an ene reaction to provide an allylic hydroperoxide followed by intramolecular transfer of oxygen catalyzed by Ti(0-i-Pr)4. The latter step is a form of Sharpless epoxidation and can be highly stereoselective. 

An easy-to-use, in situ generated catalyst resulting from a combination of commercially available, stable reagents has been reported to display a high activity in the process. The products can be easily transformed further to heterobi-cyclic derivatives, diols or tetrasubstituted alkenes (Eq. 87) [142]. 

Examples of reported hydrozirconations of alkenes and alkynes are summarized in Tables 2-6. Simple alkenes appear always to react as long as they are no more than trisubstituted. The only reported failure is that of a long chain internal alkene, triacont-15-ene, but such alkenes have subsequently been successfully hydrozirconated, albeit at slightly elevated temperature. The order of reactivity, based primarily on qualitative observations, is terminal alkene > internal alkene (cis = trans) > exocyclic alkene > cyclic alkene = trisubstituted alkene. Trisubstituted cyclic olefins and tetrasubstituted olefins do not react. Representative examples are shown in Table 2. 

Most of the examples in this chapter have been disubstituted alkenes, a few have been trisubstituted, but none so far has been tetrasubstituted (except cyclic alkenes) as this is the most difficult case of all. One solution49 starts with ethyl lactate 228 and uses a HWE reaction on the enantiomerically pure phosphonate 229 to make the / -enone 230 with very high selectivity. Chelation-controlled addition of a Grignard reagent gives the stereochemically pure allylic alcohol 231. Chelation control is explained in chapter 21. 

Complexes of the type [Ir(bzn)(cod)(L)](C104) (bzn = benzonitrile L = tricyclohexylphosphine, neomenthyldiphenylphosphine) catalyze the homogeneous hydrogenation of tetrasubstituted prochiral amido alkenes R R C=CR N. Under very mild conditions, the catalysis occurs for N = NHCOR, R = COjMe R = R = Me, R" = Me, Ph R = Me, R- = Ph, R = Me, Ph R = Ph, R = Me, R = Ph. [Ir(cod)(PCy3)(py)](PFg) serves as a catalyst in the hydroxyl-directed hydrogenation of cyclic and acyclic alkenic alcohols, wherein the reaction shows diastereoselectivity dependent on catalyst substrate stoichiometry. Park el have noted that the iridium(I)... 

The same sense of elimination to form the more stable alkene (the Saytzeff-type product) can also be observed in cyclic systems. For example, as shown in Scheme 7.30, the unstable tertiary iodide 1,2-dimethyliodocyclohexane undergoes elimination to a mixture of three alkenes, viz. 1,2-dimethylcyclohexene, 23-dimethylcyclohexene, and 2-methyl-l-methylenecyclohexane, the ratio of which (6631 3) clearly represents some kinetic partitioning between tetrasubstituted ... 

Several three-component Pd/Cu-catalyzed domino reactions with alkynes and diatyliodonium salts have been demonstrated. 2-(l-Alkynyl)-2-alken-l-ones were reacted with At2lX and alcohols to yield tetrasubstituted furans under mild conditions [248]. Cyclic diaryliodonium salts, alkynes, and aiylboronic acids could be combined to obtain exocyclic tetraaryl alkenes (Scheme 19c see Sect. 3.1.2 for a similar N-arylation cascade) [249]. 

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