1,1 -Disubstituted alkenes synthesis

Couplings between alkenyl chlorides and alkyl Grignard reagents are catalyzed best by nickel complexes,as exemplified by the synthesis of terminal alkenes, disubstituted alkenes, cyclic alkenes and a silylmethyldiene (equations 5-8),2 while Pd(PPh3)4 has also been claimed to be useful for a few... 

A interesting and useful reaetion is the intramolecular polycyclization reaction of polyalkenes by tandem or domino insertions of alkenes to give polycyclic compounds[l 38]. In the tandem cyclization. an intermediate in many cases is a neopentylpalladium formed by the insertion of 1,1-disubstituted alkenes, which has no possibility of /3-elimination. The key step in the total synthesis of scopadulcic acid is the Pd-catalyzed construction of the tricyclic system 202 containing the bicyclo[3.2. Ijoctane substructure. The single tricyclic product 202 was obtained in 82% yield from 201 [20,164). The benzyl chloride 203 undergoes oxidative addition and alkene insertion. Formation of the spiro compound 204 by the intramolecular double insertion of alkenes is an exam-ple[165]. 

Among chiral dialkylboranes, diisopinocampheylborane (8) is the most important and best-studied asymmetric hydroborating agent. It is obtained in both enantiomeric forms from naturally occurring a-pinene. Several procedures for its synthesis have been developed (151—153). The most convenient one, providing product of essentially 100% ee, involves the hydroboration of a-pinene with borane—dimethyl sulfide in tetrahydrofuran (154). Other chiral dialkylboranes derived from terpenes, eg, 2- and 3-carene (155), limonene (156), and longifolene (157,158), can also be prepared by controlled hydroboration. A more tedious approach to chiral dialkylboranes is based on the resolution of racemates. /n j -2,5-Dimethylborolane, which shows excellent enantioselectivity in the hydroboration of all principal classes of prochiral alkenes except 1,1-disubstituted terminal double bonds, has been... 

An alternative synthesis of (Z)-l-halo-l-alkenes involves hydroboration of 1-halo-l-alkynes, followed by protonolysis (246,247). Disubstituted ( )-and (Z)-a1keny1 bromides can be prepared from ( )- and (Z)-a1keny1 boronic esters, respectively, by treatment with bromine followed by base (248). 

In the earlier, longer approach to (Z)-and (E)-alkenes, ThxR BH was used iastead of IpcR BH. It is also possible to prepare a-chiral acetylenes and alkanes by this method (76,520). In a shorter synthesis of a-chiral alkynes, a prochiral disubstituted (Z)-a1kene is hydroborated with... 

Cyclotrithiazyl chloride is also a useful reagent in organic chemistry in the fusion of 1,2,5-thiadiazoles to quinones as well as the synthesis of (a) isothiazoles from 2,5-disubstituted furans and (b) bis-1,2,5-thiadiazoles from A-alkylpyrroles (Scheme 8.4). Alkenes and alkynes react readily with (NSC1)3 to give 1,2,5-thiadiazoles, while 1,4-diphenyl-1,3-butadiene gives a variety of heterocyclic products including a bis(l, 2,5-thiadiazole). ... 

This method provides a convenient synthesis of alkenes with the double bond in a relatively unstable position. Thus reduction of the p-toluenesulfonylhydrazones of a,(3-unsaturated aryl ketones and conjugated dienones gives rise to nonconjugated olefins. Unsaturated ketones with endocyclic double bonds produce olefins with double bonds in the exocyclic position. The reduction of p-toluenesulfonylhydrazones of conjugated alkynones furnishes a simple synthesis of 1,3-disubstituted allenes. ... 

The synthesis and properties of heat-resistant polyazomethines containing 2,5-disubstituted oxadiazole fragments, being insulators convertible into semiconductors by doping with iodine, have been described. The radical copolymerization of alkenes with the fluorescent co-monomer 2-/-butyl-5-(4 -vinyl-4-biphenylyl)-l,3,4-oxadiazole has resulted in useful macromolecular scintillators. Anionic polymerization of 2-phenyl-l,3,4-oxadiazolin-5-one has produced a nylon-type product <1996CHEC-II(4)268>. 

Recent studies by Grubbs on the effect of stereochemistry on synthesis of macrocyclic peptides (disubstituted alkenes) by ring closing metathesis were not disclosed at the time of our planning. See (a) Ref. 6a. (b) Miller SJ, Blackwell H, Grubbs RH (1996) J Am Chem Soc 118 9606... 

As recently demonstrated by Furstner and Langemann, higher yields of the disubstituted olefin 83 can be obtained under high dilution conditions using la as the catalyst. Our experiments clearly illustrate that synthesis of trisubstituted macrocyclic alkenes is more complicated than that of their disubstituted analogues. See Furstner A, Langemann K (1996) J Org Chem 61 3942... 

Sequential cross-coupling can be used also for synthesis of 1,1-disubstituted alkenes from 2,3-dibromopropene (Aldrich). The allylic halogen couples directly with a Grignard reagent vinylic coupling is slower and requires a catalyst (equation I). 

Lowenthal and Masamune (44) investigated the cyclopropanation of trisubsti-tuted alkenes leading to a chrysanthemic acid synthesis. They found that ligand 50c provided poor selectivities in this case (24% de for the trans isomer). Substitution in the 5 position of the oxazolines leads to increased selectivities, with excellent results provided by the BHT ester (94 6, 94% ee), Eq. 32. This ligand proved to be applicable to other trisubstituted and several cis-disubstituted alkenes, providing the corresponding cyclopropanes in ee values of 82-95%. These authors note that catalysts generated from CuOTf, CuOf-Bu, and Cu(II) precursors (with activation) provided similar yields and enantioselectivities. 

STEREOSELECTIVE SYNTHESIS OF 2,2-DISUBSTITUTED 1-FLUORO-ALKENES (E)-[lFLUORO(2-PHENYLCYCLOHEXYLlDENE)-... 

In addition to his total synthesis of pamamycin-607 (lb) (see Schemes 14-17), Kang also communicated an alternative synthesis of a larger fragment surrogate of lb [51]. Again, iodoetherifications of y-triethylsilyloxy alkenes were utilized as key transformations to control the 2,5-c/s-disubstitution of the two tetrahydrofuran moieties. However, whereas his total synthesis of lb involved a two-directional formation of both heterocycles in a single operation, the alternative route depicted in Schemes 31 and 32 is characterized by sequential... 

A modification of an earlier procedure for debromination of v/c-dibromides in the presence of catalytic amounts of diorganotellurides has allowed the synthesis of terminal alkenes and cis- and frani-l,2-disubstituted alkenes from appropriate precursors the relative substrate reactivities suggest that, as for the stoichiometric reaction, the catalytic reaction involves intermediate bromonium ion formation. The Te(IV) dibromides formed in the debrominative elimination are reduced back to the catalysts by either sodium ascorbate or the thiol glutathione. 

In more recent work, Chiu and co-workers [167, 168] have reported an intramolecular 1,3-dipolar cycloaddition approach toward the pseudolaric acids 85, in which the di-polarophile is an unactivated 1,1-disubstituted alkene. Hence, treatment of the diazo ketone 86 with catalytic Rh2(OAc)4 furnished a mixture of tricyclic products 87 and 88 in nearly equal proportions (Scheme 19.13). The synthesis of 2-pyridones [169] and their application to the ipalbidine core [170] has been described. The pentacyclic skeleton of the aspidosperma alkaloids was prepared via the cycloaddition of a push-pull carbonyl ylide [171]. The dehydrovindorosine alkaloids 89 have also been investigated, in which the a-diazo-/ -ketoester 90 undergoes a facile cycloaddition to furnish 91 in... 

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