Trisubstituted olefins, preparation

The regiochemistry of the hydrozirconation of disubstituted stannyl- [24, 167-170] and silyl- [171] acetylenes and boron- [118, 172-175] and zinc- [34, 126] alkynyl derivatives result in the formation of 1,1-dimetallo compounds. Hydrozirconation of alkynyliodonium salts affords alkenylchlorozirconocenes with the Zr-C bond geminal to the iodonium moiety [176]. These zirconocene complexes allowed the preparation of ( )-trisubstituted olefins (Scheme 8-20). 

Trost reported the synthesis of 1,4-dienes with ruthenium catalysis through regioselective carbometallation of alkynes with alkenes.51 Di- and trisubstituted olefins can also be obtained with arylboronic acids through an intermolecular process under rhodium,30 52 55 nickel,56 and palladium catalysis.57 Recently, Larock has reported an efficient palladium-catalyzed route for the preparation of tetrasubstituted olefins.58,59... 

As depicted in Scheme 21, subjection of 86 with 20 mol% of freshly prepared 2 after 4 h at 22 °C indeed afforded 87 in 92% yield after silica gel chromatography (>98% Z). Stereocontrolled hydrogenation of the trisubstituted olefin (72% yield) and removal of the acetate and trifluroacetate groups, effected by subjection of the hydrogenated adduct with hydrazine in MeOH, delivered Sch 38516 (1) in 96% yield to complete the total synthesis. 

While Table 1 is an important tool for many of the studies, the current trend is to elaborate more the increasingly difficult substrates within a particular class of olefins. Andersson and coworkers have published several variations of the 1, 2-diaryl substrate 25a for the fairly more difficult 1,1 diaryl class of trisubstituted olefins (Scheme 3) [45]. The authors note that the products form an important class of compounds that are pharmaceutically relevant and difficult to prepare by other available methods. 

Chiral l,T-diphosphetanylferrocene Et-FerroTANE serves as an effective ligand for the rhodium-catalyzed hydrogenation of y9-aryl- and /9-alkyl-substituted monoamido ita-conates (Eqs. 19 and 20) [54]. The Et-DuPhos-Rh catalyst was utihzed for the asymmetric hydrogenation of the trisubstituted olefin derivative in the preparation of an important intermediate for the drug candoxatril (>99% ee) [110]. 

Similarly, the reaction of 1-chloropentyhnagnesium chloride (56), derived from 1-chloro-l-iodopentane, with a-sulfonyl lithium carbanions (52) affords 1,2-di- or 1,1,2-trisubstituted olefins (57) in moderate to good yields (equation 14). This reaction represents an elegant preparation of olefins from sulfones. 

A combination of both of the procedures described above results in the preparation of trisubstituted olefins.347 The entire conversion of haloalkyne to 82 can be carried out in one... 

Many other variations of the basic structure 10 have been explored, including an-hydro sugars and carbocyclic analogs, the latter derived from quinic acid 13 [23-26]. In summary, the preparation of these materials (e.g. 14-16) requires more synthetic effort than the fructose-derived ketone 10. Occasionally, e.g. when using 14, catalyst loadings can be reduced to 5% relative to the substrate olefin, and epoxide yields and selectivity remain comparable with those obtained by use of the fructose-derived ketone 10. Alternative ex-chiral pool ketone catalysts were reported by Adam et al. The ketones 17 and 18 are derived from D-mannitol and tartaric acid, respectively [27]. Enantiomeric excesses up to 81% were achieved in the epox-idation of l,2-(E)-disubstituted and trisubstituted olefins. 

Similar reaction conditions allowed the preparation of a-branched nitriles (Fig. 83). When mono-, di-, and trisubstituted olefins 355 bearing functionalities, such as esters, aldehydes, ketones, amides, or alcohols, were reacted with tosyl cyanide 356 and phenylsilane in the presence of 1 mol% of the (salen)Co catalysts 357a or 357b the corresponding nitriles 358 were isolated in 55-99% yield (entry 21) [402]. Although no mechanistic evidence was provided, the reaction may be assumed to proceed similarly as the hydroazidation. 

What procedures aTfe available for the preparation of trisubstituted olefins ... 

A similar procedure can be applied to the synthesis of a series of 5-nitroimidazoles83 with antibacterial properties.The S l reaction of various l-alkyl-2-chloromethyl-5-nitroimidazoles (23) with heterocyclic nitronate anions prepared from 3-nitrolactams, under phase transfer catalysis, afforded trisubstituted olefins (equation 33). 

Corey and Yamamoto 233) used the P-oxido synthesis 2341 of trisubstituted olefins for the preparation of the acyclic sesquiterpene famesol 433. In this preparation the isoheptenylphosphonium salt 430 is converted into the hydroxyfamesol derivative 432 by reaction with the tetrahydropyranyl ether — protected hydroxy aldehyde 431 and formaldehyde 205. 432 is converted into famesol 433 via several steps. Other reactions of432 likewise proceeding via several steps lead to 434 which is a positional isomer of a C17-juvenile hormone 233) (Scheme 75). 

More recently this procedure has been expanded to include some trisubstituted olefins (Asveld and Kellog, 1980). The wide applicability of these procedures to the preparation of dioxetanes of diverse structure, and what proved to many workers to be a surprising stability of most alkyl- and alkoxy-substituted dioxetanes, have facilitated their study and contributed to the tremendous amount of activity in the field. To date well over 100 dioxetanes have been prepared and scrutinized with the objective of elucidating the mechanistic details of their remarkable transformation to excited state carbonyl-containing products. 

THF at - 20°. All other anions should be prepared separately, and 2 should be added to 1 at - 20°. By these procedures mono- and disubstituted olefins, vinyl sulfides, vinyl ethers, and allylsilanes are available in 35-80% yield, usually as cis-trans mixtures. Trisubstituted olefins are best prepared by similar routes from a -branched nitrile anions. 

D-Fmctose-derived ketone 50 (also available in its enantiomeric form from L-sorbose) was introduced as a catalyst for the asymmetric epoxidation of trans- and trisubstituted olefins, and as such was successful in the preparation of enantioenriched substituted cycloalkene oxides (Table 5, entries 1-5) <1996JA9806, 1997JA11224, 2001T5213>. 

Polymer-supported peracids are also used effectively for the epoxidation of di-and trisubstituted olefins. The ratio of the stereoisomers is similar to that for the products of the reaction of the monomer with aromatic peracids. MCPBA epoxidation of homoallyl phosphonates has led to the preparation of 3,4-epoxyalkane phosphonates 39 in addition to the 1,2- and 2,3-epoxy derivatives.Stereospecific peracid oxidation is one of the preparative methods employed in the synthesis of the structurally varied cyclic polyoxirane isomers, which are of interest from a biological aspect. ... 

Cinnamic esters or amides prepared from optically active alcohols (menthol, aryl ethanol) or amines are hydrogenated to products in only low optical yields (less than 40%). Camphor sultam is a much better rr-face discriminator and the hydrogenation of the trisubstituted olefinic bond of sultam-imides over Pd-on-carbon affords, after saponification, j3-substituted carboxylic acids in high e.e. (>95%) ... 

---