Alkene 1,2-unsymmetrically disubstituted

The stereochemistry with respect to the ketene iminium salt in cases of monosubstituted or unsymmetrically disubstituted derivatives in cycloadditions to alkenes show differences from the ketene counterpart. In contrast to ketene cycloadditions of monosubstituted ketenes with alkenes where the substituent in the bicyclic derivative ends up in the endo position, the cycloaddition of two monosubstituted ketene iminium salts with cyclopentene and cyclohexenc gives the e.wp-substituted derivatives 4.6... 

The above inconveniences are circumvented by the application of substituted borane derivatives, e.g., Sia2BH and 9-BBN (see Fig. 1 for definitions), which react with high regioselectivity and sensitivity to steric factors. Thus, 1-alkenes and 1-alkynes are hydroborated at the terminal position. The internal unsymmetrically disubstituted alkenes are also selectively hydroborated. The clean transformation of 1-alkynes into vinylboranes—not possible with borane—can be achieved with these reagents (Fig. 2). 

Highest regio- and stereoselectivity among all boranes is exhibited by 9-BBN. Terminal alkenes are transformed into the corresponding B-alkyl-9-BBN derivatives in purities approaching 100%. Unsymmetrically disubstituted alkynes and alkenes also react selectively . Addition to 3-methylcyclohexene and 3-methylcyclopentene gives no cis-1,2-isomer . 1,3-Dialkylcycloalkenes are transformed into single stereo isomers . 

Mixtures of cyclobutanones are formed from unsymmetrical disubstituted ketenes. The extent of stereoselectivity depends on the size difference of the substituents. The larger substituent on the ketene ends up in the more hindered position in the major product9,12a. Z-Alkenes are also more reactive than A-alkcnes in these cycloadditions as a consequence of the transition state10 2. 

Phosphonic mono- and di-amides have been widely examined as substrates in the WEH reaction with the considerable success in the use of their carbanions in the non-stereose-lective synthesis of (j5-hydroxyalkyl)phosphonic diamides the result of decreased elec-trophilicity of the phosphorus atom. The fission of such diamides occurs when they are heated in a high-boiling solvent the separated threo and erythro stereoisomers from, for example, benzylic phosphonic diamides undergo decomposition into ( )- and (Z)-alkenes, respectively, although the exact mechanism is unclear The successful release of alkene from the thiophosphinic amide 175 is possible after methylation to 176 the yields of unsymmetrical disubstituted alkenes are 50 99%, and even for tri- and tetra-substituted alkenes yields of 53-93% are achievable . 

In Scheme 21, the regioselective (and stereoselective) intramolecular addition of a 1,2-unsymmetrically disubstituted alkene to an Al-acylindole is used to achieve a formal synthesis of the alkaloid vindorosine 59 [53]. The key step is formation of cycloadduct 60, which undergoes in situ retro-aldol opening to 61. The face selectivity of attack of the alkene on the indole is governed by the size of the R2 substituent. 

The order of reactivity of halides and triflates for the cross-coupling reaction of boron reagents is 1 > Br > OTf Cl. Thus, the sequential cross-coupling reactions of 4-bromophenyl triflate with two 9-alkyl-9-BBN derivatives obtained from two different alkenes furnishes the unsymmetrically disubstituted benzene derivative (Scheme 18). ... 

With unsymmetrically disubstituted alkenes of type 51, two regioisomeric products were obtained, but the isomer 53 bearing the alkoxycarbonyl group adjacent to the spiro carbon atom was the minor component in all cases. Norbomadiene and norbomene reacted with 50 by the same mode to give formal [3 + 2] cycloadducts 54 and 55, 56, respectively, the latter as a 9 1 mixture of exo-55 and cndo-isomers 56 (Scheme 15). In... 

While monosubstituted alkenes usually react with high regioselectivity, it is not true for disubstituted alkenes. Formation of mixtures of type 163 and 164 (equation 105) has been observed in most cases when unsymmetrical alkenes bearing two different substituents possess similar stereoelectronic properties. In general, regioselectivity is controlled by a combination of HOMO-LUMO interactions, steric effects and hydrogen bonding between suitable substituents in both alkene and nitrone molecules . ... 

The hydroboration of an olefin involves a cis addition of a boron-hydrogen bond to an alkene linkage, and for unsymmetric olefins occurs in a counter-Markownikoff fashion. 1-Alkenes and simple 1,2-disubstituted olefins undergo rapid conversion to the corresponding trialkylborane, whereas addition of diborane to tri- and tetrasubstituted olefins may be conveniently terminated at the respective di- and monoalkylborane stage. 1-Alkenes yield trialkylboranes in which there is a preponderant (approximately 94%) addition of the boron atom to the terminal carbon.2,3... 

Symmetrical and unsymmetrical aldazines are converted to 2,5-disubstituted 1,3,4-oxadiazoles by oxidation with bis(trifluoroacetoxy)iodobenzene in yields ranging from 49 to 80%.146 Lithium bromide catalyses efficiently the dihydroxylation of alkenes... 

The preparation of unsymmetrically terminally disubstituted 1,3,5-hexa-trienes by twofold Heck coupling of 162-m with two different alkenes cannot be achieved, since the second coupling step turned out to be significantly faster than the first one [96]. Sufficient differentiation could not be brought about with a triflate and a bromide leaving group as in 168. How-... 

Unsymmetrical silaketals 201 having a 1,2-disubstituted double bond and a nitro group were prepared and transformed upon treatment with phenyl isocyanate in the presence of Et3N under mild reaction conditions into 2-oxazoline derivatives 202 by a regiospecific intramolecular 1,3-dipolar cycloaddition, as shown in Scheme 36 <1997SL1208>. The /ra r-stereochemistry of the alkene 201 was transported to the 2-isoxazoline product 202, which was confirmed by the H NMR spectroscopic data. 

Thermal fragmentation of 2,5-disubstituted tetrazoles results in loss of Na and generation of a reactive nitrilimine intermediate (67). The Hammett p-values for the A -phenyl and C-phenyl rings of diaryltetrazoles (65) were +1.16 and -0.23, respectively, suggesting an unsymmetrical transition state of type (66) (68X3787). Subsequent additions of the nitrilimines to unsaturated bonds such as alkenes, imines, alkynes and nitriles give an added importance to the parent tetrazoles as synthetic precursors (Scheme 6). Among the most... 

Nitrile oxides undergo efficient [3-1-2] cycloadditions with alkynes and alkenes to generate isoxazoles and 4,5-dihydroisoxazoles, respectively. With unsymmetrical dipolarophiles there exists the possibility of regioisomeric mixtures of products however, it is generally found that steric effects control the regioselectivity and the more encumbered end of the dipolarophile becomes attached to the oxygen of the nitrile oxide. Thus, terminal alkynes and alkenes afford almost exclusively 3,5-disubstituted isoxazoles and dihydroisoxazoles, respectively (Scheme 91). 

Tosylmethyl isocyanide (TosMIC) (75 R = H), a versatile reagent in synthesis, can also be used as an acyl anion equivalent. For instance symmetrical and unsymmetrical diketones were prepared by using this TosMIC synthon (equation 40). Ketones are homologated to enones by alkylating the condensation product derived from TosMIC, followed by acid hydrolysis (Scheme 46). 1-Isocyano-l-tosyl-l-alkenes (76), formed by the reaction of TosMIC with an aldehyde or ketone, react with a primary amine or ammonia to give 1,5-disubstituted (or 5-monosubstituted) imidazoles in high yield (Scheme 47). ... 

Monohydroboration of unsymmetrically dialkylsubstituted alkynes with dialkylboranes produces mixtures of regioisomeric alkenylboranes. However, their protonolysis leads to cA-disubstituted alkenes. 

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