Tri-Substituted Alkenes

Matterstock, K., (Farbwerke Hoechst, A.G.), unpublished results. Graf. R., ngew. Chem. Int. Ed. Engl., 7, 172 (1968). 

---

The majority of intrazeolite photooxygenations have been conducted in NaY,84 85 however, one study in the pentasil zeolite ZSM-5 demonstrates that steric confinement effects can play important roles.84 A comparison of the reactions of a series of tri-substituted alkenes in isooctane, NaY, and in ZSM-5 is given in Fig. 21. The reactions... 

Table 6.2 Enantioselective hydrogenation of tri-substituted alkenes catalyzed by [(S,S,S)-(EBTHI)TiX2].a)...

In the case of tri-substituted alkenes, the 1,3-syn products are formed in moderate to high diastereoselectivities (Table 21.10, entries 6—12). The stereochemistry of hydrogenation of homoallylic alcohols with a trisubstituted olefin unit is governed by the stereochemistry of the homoallylic hydroxy group, the stereogenic center at the allyl position, and the geometry of the double bond (Scheme 21.4). In entries 8 to 10 of Table 21.10, the product of 1,3-syn structure is formed in more than 90% d.e. with a cationic rhodium catalyst. The stereochemistry of the products in entries 10 to 12 shows that it is the stereogenic center at the allylic position which dictates the sense of asymmetric induction... 

The highest enantioselectivity in the hydrogenation of unfunctionalized tri-substituted alkenes has been achieved with catalyst 14 a. The same catalyst was also used to hydrogenate a,/ -unsaturated phosphonates with enantiomeric excesses (ee) of 70 to 94% [8]. 

By comparison, the diphosphine analogue [Ir(cod)(P-MePl RIPFf, was less active by a factor of two for tri-substituted alkenes and a factor of eight for tetrasub-stituted ones whilst the analogous bispyridine complex showed no activity at all, apparently due to a failure to add H2. 

Substitution of alfylic sulfoxides. Lithium dimethyl cuprate and di-n-butyl cuprate react with allylic sulfoxides or sulfones mainly by y-substitution to give tri-substituted alkenes (equation I).15... 

Although terminal alkenes provide the best yields, the Ritter reaction is also successful when using tri-substituted alkenes and haloalkenes. Markovnikov addition is generally observed. Rearranged products arise occasionally, especially with alkenes that are prone to cationic rearrangements (equation 165).233... 

The overall process is generally highly regiospecific. Mono- or di-substituted terminal alkenes and tri-substituted alkenes afford >99% of the Markovnikov adduct (equation 206).312-314... 

A catalytic asymmetric oxidation of mono-, di-, and tri-substituted alkenes using a chiral bishydroxamic acid (BHA) complex of molybdenum catalyst in air at room temperature leads to good to excellent selectivity. It has been suggested that the Mo-BHA complex combines with the achiral oxidant to oxidize the alkene in a concerted fashion by transfer of oxygen from the metal peroxide to the alkene.78 The chiral BHA-molybdenum complex has been used for the catalytic asymmetric oxidation of sulfides and disulfides, utilizing 1 equiv. of alkyl peroxide, with yields up to 83% and ees up to 86%. An extension of the methodology combines the asymmetric oxidation with kinetic resolution providing excellent enantioselectivity (ee = 92-99%).79... 

A ruthenium based catalytic system was developed by Trost and coworkers and used for the intermolecular Alder-ene reaction of unactivated alkynes and alkenes [30]. In initial attempts to develop an intramolecular version it was found that CpRu(COD)Cl catalyzed 1,6-enyne cycloisomerizations only if the olefins were monosubstituted. They recently discovered that if the cationic ruthenium catalyst CpRu(CH3CN)3+PF6 is used the reaction can tolerate 1,2-di- or tri-substituted alkenes and enables the cycloisomerization of 1,6- and 1,7-enynes [31]. The formation of metallacyclopentene and a /3-hydride elimination mechanism was proposed and the cycloisomerization product was formed in favor of the 1,4-diene. A... 

Electronic Effects. Singlet oxygen is an electrophilic oxidant that exhibits a clear preference for reactions with nucleophilic substrates. This preference is strikingly evident in a comparison of the rates constants for ene reactions of simple methyl substituted alkenes 2,3-dimethyl-2-butene (A = 2.2 x 107M-1s-1) [19] reacts more than 30 times faster than the tri-substituted alkene 2-methyl-2-butene (k = 7.2 x 105 M-1s-1) [19] and more than 500 times faster than the di-substituted alkene Z-2-butene ( = 4.8 x 104M-1s-1) [19]. The practical implications of these electronic effects are... 

Zweifel and his co-workers have also introduced a stereospecific synthesis of tri-substituted alkenes (Eq. 75) U7 135), although it has limitations of the use. 

With diamine (25), 1-heptene afforded (/ )- ,2-heptanediol as the major ixoduct (86% ee) in 75% yield by this procedure but, curiously, oxidation of ( )-stilbene proceeded with lower optical yield (34% ee). Particularly efficient enantioface differentiation was achieved in the reaction of ( )-l-phe-nylpropene with a stoichiometric amount of osmium tetroxide in the presence of 1 mol equiv. of (-)-(27) when essentially optical pure (>99% ee) (15,2S)-l-phenylpropane-l,2-diol was obtained in 73% yield. This procedure is effective for mono-, ( )-di- and tri-substituted alkenes, with enantioface selection being as shown in Scheme 2 but, notably, the oxidation of (Z)-alkenes does not give satisfactory optical yields. 

Two related procedures employing osmium in catalytic quantities, and providing, unlike the above, a removable nitrogen substituent, have been developed. Scheme 51 represents a procedure suitable for mono- and 1,2-di-substituted alkenes, but which is too vigorous for diethyl fumarate and enones Scheme 52 is suitable for 1,1-di- and tri-substituted alkenes Scheme 53 is applicable to mono- and... 

Allylic alcohol (166) is the product of right-to-left linear iteration by this process. Not only is the tri-substituted alkene accessible with high stereochemical control, but also the ( )-disubstituted alkene is readily prepared. These linear polyenes play an important role in the biomimetic synthesis of steroids and higher terpenes. ... 

See ref. 272a for an excellent discussion of all aspects of the Julia coupling, as well as additional examples of ( )-di- and -tri-substituted alkenes, and ( , )-dienes. 

Lactones are normally stable compounds, which have found ample application as synthetic intermediates, and, quite recently, have been detected as the central structural unit in physiologically active natural products like obaflorin (123) and lipstatin (124). Characteristic applications of 3-lactones in synthesis are the stereospecific CO2 elimination to form di- and tri-substituted alkenes (e.g. from 125 equation 40) or Grignard addition to the carbonyl group e.g. equation 41). Particularly useful is the formation of 3-lactone enolates (126), which react with a variety of electrophiles (EX) wiA high stereocontrol (equation 42). Organocuprates may be used in chain elongations to form 3-branched carboxylic acids (equation 43). ... 

The stereoisomeric mixture of -hydroxyalkyl selenides resulting from the reaction of the a-selenoalkyllithium and the carbonyl compound has been often cleanly and easily separated into its constituents by liquid chromatography on silica gel (Schemes 124,133,134, and 170 172).200.206.222,226,229,258 59 jj,jg has, therefore, allowed the synthesis of each of the two stereoisomers of various di- and tri-substituted alkenes (Schemes 124,170 and 171 Scheme 172, a) and epoxides (Scheme 124 Scheme 172, b), which are otherwise obtained as intractable mixtures of stereoisomers through the conventional phosphorus or sulfur ylide methods. Last but not least, 2-lithio-2-methylselenopropane can be used as the precursor of various compounds bearing gem dimethyl substituted carbons, such as squalene, oxido-squalene, lanosterol and cholesterol. Use of commercially available perdeuterated or Ci or — 2 acetone allows the straightforward synthesis of the corresponding labelled compounds... 

Still s original communication demonstrated that this approach was elective for the synthesis of tri-substituted alkenes by the reaction of a methyl-substituted Wittig reagent with an aldehyde. Examples of the synthesis of methyl-trisubstituted alkenes are presented in Table 16. 

Emmons reaction (Scheme 26). ° Horner-Wadsworth-Emmons reactions also feature in new routes to (diphenylphosphono)acetic acid esters and alkenes. The latter involve combining the Homer-Wadsworth-Emmons procedure with a Heck coupling reaction for the synthesis of tri-substituted alkenes. 

In view of the last example, you should not be surprised that the non-conjugated diene 45 reacts with mCPBA at the more highly (tri-) substituted alkene to give the epoxide 33 in good yield.5... 

Thermal and SnCU-catalyzed ene reactions of diethyl dioxomalonate have been extensively explored by Salomon. The use of clay as a catalyst for this reaction has also been reported. Mono-, 1,1-di-, 1,2-di- and tri-substituted alkenes afford ene adducts upon heating with 1 equiv. of diethyl oxomalonate at 80-185 C for 1-340 h. Ene adducts can also be obtained in comparable yield with SnCU at 0 C. The enophile approaches the alkene from the less-hindered face. Endolexo stereoisomerism is not possible... 

---