Alkenes regioselective synthesis

Negishi et al. reported the regioselective synthesis of diisoalkyl derivatives from monosubstituted alkenes in yields ranging from 58-95%, Scheme 8, from the in situ prepared ethylene complex Cp2Zr(C2H4).35 The zirconocene-ethylene complex presumably undergoes alkene insertion to furnish a zirconacyclopentane which further reacts with diethylzinc to yield the diisoalkylzinc compound. 

Stereo- and regioselective synthesis of trienes and tetraenes has been reported by palladium-catalysed coupling of (E)- or (Z)-l-alkenyl boronates with (E)- or (Z)-2-bromo-1-phenylthio-l-alkenes followed by treatment with a Grignard reagent in the presence of a nickel catalyst (equation 146)259. 

Highly reactive metallic titanium, prepared from TiCb and potassium, reduces enol phosphates to alkenes, permitting regioselective synthesis of dienes from a,p-unsaturated ketones. ... 

Allyl sulfones have been used in a large number of valuable syntheses, but notably in the synthesis of alkenes, dienes and polyenes. Thus a-alkylallyl tolyl sulfones afford terminal alkenes regioselectively when treated sequentially with 2 equiv. of tin hydride and concentrated hydrochloric acid (Scheme 117, entry Allyltin derivatives, which are intermediates in this transformation, can be isolated if the acidic treatment is omitted (Scheme 117, entry a). 

Rapid development in the Heck reaction has made it one of the most important of all modem methods. A dramatic example is a recent synthesis of strychnine by M. Nakanishi and M. Mori.23 This synthesis illustrates the intramolecular Heck reaction particularly well, showing examples of regioselectivity in attack on the alkene and in formation of the new alkene. The synthesis starts with a Heck reaction on enantiomerically pure 149. Attack occurs on the nearer end of the alkene to give 150 that cannot eliminate to reform the same alkene as there are no H atoms left and the alkene 151 must be formed. The stereochemistry is controlled by the short tether linking the aryl bromide and the alkene. 

Treatment of terminal acetylenes with hydrogen iodide, generated in situ from TMSCl, sodium iodide, and water, provides a highly regioselective synthesis of 2-iodo-l-alkenes. Followed by addition of cuprous cyanide, the protocol offers a convenient one-pot preparation of 2-substituted acrylonitriles in fair to good yield (eq 90). In contrast, when the reaction with arylacetylene proceeds in DMSO and with catalytic amount of sodium iodide, the 3-arylpropynenitrile is obtained as the preferred product. 

Synthesis of Heterocycles via Addition to Alkenes and Alkynes. The regioselective synthesis of heterocycles has been demonstrated using both cyclohexenyl phenols and anilines in which the products differ in both cases by either a 5-exo-trig or 6-endo-trig cyclization. For the phenolic substrate, the 6-endo cyclization product was formed exclusively, while under almost identical conditions, the aniline gave only the 5-exo cyclization (eqs 28 and 29). Similarly, hydroxycoumarin derivatives also cyclize in a 6-endo fashion similar to the cyclohexenylphenols. ... 

Indazoles were prepared by many different methods. Indazoles 41 were synthesized from nitroaromatics 39 and N-tosylhydrazones 40 with bases (14CC5061). A rhodium(III)-catalyzed oxidative olefination of 1,2-di-substi-tuted arylhydrazines with alkenes via sp C-H bond aaivation followed by an intramolecular aza-Michael reaction yielded indazoles (140L2494). Copper-catalyzed C-H amidation with aromatic imines 42 with tosyl azide provided a route to 3-substituted indazoles 43 (14OL4702). 4,5,6,7-Tetrahydro-lH-inda-zol-3-(2fJ)-one derivatives were prepared in two-step one-pot process (14SC1076). A regioselective synthesis of 2H-indazoles 45 was achieved using... 

Shimizu K, Takimoto M, Sato Y, Mori M (2005) Nickel catalyzed regioselective synthesis of tetrasubstituted alkene using alkylative carboxylation of disubstituted alkynes. Org Lett 7 195-197... 

Because borane additions to double bonds and subsequent oxidation are so selective, this sequence allows the stereospeeific and regioselective synthesis of alcohols from alkenes. The anti-Markovnikov legioselectivity of the hydroboration-oxidation sequence complements that of acid-catalyzed hydration and oxymercuration-demercuration. In addition, hydroboration, like oxymercuration, occurs without the participation of carbocations therefore, rearrangements are not observed. 

Regioselective synthesis of indoles is accomplished by in situ trapping of Wacker aldehydes with (1) (eq 4). o-Vinylacetanilides give indoles directly under similar reaction conditions. Iso-coumarins and 1-isoquinolinones are also prepared by this chemistry. Electron-deficient alkenes give acetals with (1) under Wacker conditions (see PaUadium(H) Chloride-Copper(I) Chloride) ... 

Desulfonylation of equally substituted allylic sulfones with NaBH4 and LiBHEt3 usually yields a mixture of regioisomeric alkenes[406,407]. However, the regioselective attack of the less substituted side of the unsymme-trically substituted allylic system with LiEtjBH has been utilized for the removal of the allylic sulfone group in synthesis of the polyprenoid 658[408],... 

With a regioselectivity opposite to that of the Zaitsev rule the Hofmann ehmma tion IS sometimes used in synthesis to prepare alkenes not accessible by dehydrohalo genation of alkyl halides This application decreased in importance once the Wittig reac tion (Section 17 12) became established as a synthetic method Similarly most of the analytical applications of Hofmann elimination have been replaced by spectroscopic methods... 

Cycloaddition involves the combination of two molecules in such a way that a new ring is formed. The principles of conservation of orbital symmetry also apply to concerted cycloaddition reactions and to the reverse, concerted fragmentation of one molecule into two or more smaller components (cycloreversion). The most important cycloaddition reaction from the point of view of synthesis is the Diels-Alder reaction. This reaction has been the object of extensive theoretical and mechanistic study, as well as synthetic application. The Diels-Alder reaction is the addition of an alkene to a diene to form a cyclohexene. It is called a [47t + 27c]-cycloaddition reaction because four tc electrons from the diene and the two n electrons from the alkene (which is called the dienophile) are directly involved in the bonding change. For most systems, the reactivity pattern, regioselectivity, and stereoselectivity are consistent with describing the reaction as a concerted process. In particular, the reaction is a stereospecific syn (suprafacial) addition with respect to both the alkene and the diene. This stereospecificity has been demonstrated with many substituted dienes and alkenes and also holds for the simplest possible example of the reaction, that of ethylene with butadiene ... 

The overall result of the sequence hydroboration -I- oxidation is a regioselective and-Markownikoff-addition of water to an alkene. This reaction is an important method in organic synthesis, since it can be made stereoselective and even enantioselective. 

In practice simple alkenes give poor cycloaddition so diene (49) was the chosen starting material and the aldol was protected and hydrogenated to give (48). Note that (50) is emphatically bowl shaped (Chapter T 34) so that substituents (OR) or reagents (Hg) prefer to be on the outside of the bowl. The regioselectivity of the addition of Cl2C=C=0 to the diene (49) is correct. Synthesis ... 

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