Regioselectivity and Diastereoselectivity

Diborane as well as mono- and dialkylboranes give cis addition in reactions with alkenes, as noted above, which is a result of the four-center transition state in which the boron and hydrogen are delivered from the same face, illustrated by hydroboration of 1-methylcyclopentene with R2BH to give 19. The methyl-bearing 

When the alkene is internal and unsymmetrical, as in 3-methyl-1-cyclohexene (22), the reaction is more complicated. In addition to the two faces (top and bottom) of the molecule, there are two different and reactive sp carbons of the alkene. Hydroboration leads to four products, 23, 24, 25, and 26. With diborane 

Stereoselectivity in addition reactions of borane with bicyclic alkenes is similar to that observed for reduction of bicyclic ketones with hydride reducing agents. Boranes add to norbornene derivatives from the exo face (27 gave 85% exo attack upon reaction with diborane). In 27-30, all values are percentage yields of the organoborane products obtained by reaction from that face. Interestingly, only 80% exo attack was observed when 27 reacted with disiamylborane, and the size of the borane appears to have little effect on selectivity. 

When the alkene is part of an edge fused bicyclic system (bicyclo[m.n.0] systems), the regio- and stereoselectivity is influenced by the conformation of the molecule and the relative stereochemistry of the substituents. Hydroboration of 31, in Heathcock s synthesis of eudesmanes, led to a 66 34 mixture of boranes with attack from the top face predominating (giving 32). 19,15 

Dialkylboranes can disproportionate, although hindered alkylboranes are relatively stable, and this limits their utility in reactions with alkenes. One solution to this problem was the discovery that boranes containing heteroatoms stabilize the borane and are easy to prepare. Diborane reacts with alcohols such as methanol to 

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Electron-deficient 1,3-dienes are known to react when heated with metho-xy(aryl)- or methoxy(alkyl)carbene complexes to afford vinylcyclopropane derivatives with high regioselectivity and diastereoselectivity [8a, 24]. Cyclo-propanation of the double bond not bearing the acceptor functional group and... 

High pressure can influence reactions characterized by negative molar and activation volumes in the following aspects (i) acceleration of the reaction, (ii) modification of regioselectivity and diastereoselectivity, and (iii) changes in chemical equilibria. The pressure dependence on the rate constant of the reaction is expressed as follows ... 

A systematic exploration of the intramolecular [4+2]/[3+2] cycloaddition cascade of 1,3,4-oxadiazoles was described. The studies permit the use of unsymmetrical dienophiles, dipolarophiles, and oxadiazoles as well as to control the cycloaddition regioselectivity and diastereoselectivity. The scope and utility of the reaction were defined <2006JA10589>. The tandem intramolecular [4+2]/[3+2] cycloaddition cascade reaction of 1,3,4-oxadiazole was applied to the syntheses of a series of natural products including a total synthesis of (-)- and ent-(+)-vindoline <2006JA10596>. 

Having established that pure enantiomer ( S,ZR)-77 was capable of undergoing remarkably regioselective and diastereoselective C-H activation, it followed that highly efficient enantiomeric differentiation of rac-77 could be accomplished.199 Hence, the Rh2(5Y-MEPY)4-catalyzed reaction of rac-77 effectively gave close to a 1 1 mixture of enantioenriched (lY)-78 (91% ee) and ( R)-79 (98% ee) (Equation (68)). Other equally spectacular examples of diastereo- and regiocontrol via chiral rhodium carboxamide catalysts in cyclic and acyclic diazoacetate systems have been reported.152 199 200 203-205... 

Stratakis, M., Sofikiti, N., Baskakis, C. and Raptis, C. (2004). Dye-sensitized intrazeolite photooxygenation of 4-substituted cyclohexenes. Remote substituent effects in regioselectivity and diastereoselectivity. Tetrahedron Lett. 45, 5433-5436... 

TABLE 24. Regioselectivity and diastereoselectivity in the photooxygenation of chiral alkenes within zeoUte Na-Y and in solution (values in parentheses)... 

SCHEME 56. Na -directing regioselectivity and diastereoselection in the intrazeolite photooxygenation of a-terpinyl acetate... 

A. RasteUi, R. Gandolfi, and M. Sarzi-Amade, Regioselectivity and Diastereoselectivity in the 1,3-dipolar Cycloadditions of Nitrones with Acrylonitrile and Maleonitrile. The Origin of ENDO/EXO Selectivity , in Advances in Quantum Chemistry, Vol. 36, Academic Press, New York, 1999, pp. 151-167. 

Chemoselectivity, regioselectivity, and diastereoselectivity in benzonitrile oxide cycloadditions... 

Desymmetrization of an achiral, symmetrical molecule through a catalytic process is a potentially powerful but relatively unexplored concept for asymmetric synthesis. Whereas the ability of enzymes to differentiate enantiotopic functional groups is well-known [27], little has been explored on a similar ability of non-enzymatic catalysts, particularly for C-C bond-forming processes. The asymmetric desymmetrization through the catalytic glyoxylate-ene reaction of prochiral ene substrates with planar symmetry provides an efficient access to remote [28] and internal [29] asymmetric induction (Scheme 8C.10) [30]. The (2/ ,5S)-s> i-product is obtained with >99% ee and >99% diastereoselectivity. The diene thus obtained can be transformed to a more functionalized compound in a regioselective and diastereoselective manner. 

W. Adam, C. R. Saha-Moller, and K. S. Schmid, Synthesis of 4,6-dideoxyfuranoses through the regioselective and diastereoselective oxyfunctionalization of a dimethylphenylsilyl-substituted chiral homoallylic alcohol, J. Org. Chem., 66 (2001) 7365-7371. 

In 1990, Griesbeck and Stadtmiiller [46] found that the reaction of benzalde-hyde with homoallylic alcohols did not show diastereoselectivity. Ten years later Adam and co-workers showed that allylic alcohols reacted with benzophenone to give the corresponding adducts with high regioselectivity and diastereoselectivity (Scheme 3.40) [78-80]. 

Adam and coworkers reported the regioselective and diastereoselective formation of oxetanes during the PB reaction of allylic alcohols (Scheme 7.27) [43, 44]. This group proposed that hydrogen-bond interactions in the exciplex played an important role in controlling the selectivity. D Auria and coworkers also observed a site-selective and diastereoselective formation of oxetanes in the PB reaction of 2-furylmethanol derivatives (Scheme 7.27) [45]. 

Scheme 7.27 Regioselective and diastereoselective formation of oxetanes in the PB reaction of allylic alcohols.

Photoinduced [2+2] cycloadditions of lH-l-acetylindole-2,3-dione (13) with alkenes gave spiro-oxetanes 14 in moderate to high yields, displaying the typical triplet n-n reactivity of acetylisatin (Sch. 3) [18]. The regioselectivity and diastereoselectivity of these reactions depends on the... 

The regioselectivity and diastereoselectivity can be interpreted in terms of a six-membered chairlike transition state8(Scheme 3.20. Thus, the nucleophilic attack of a fluoride anion to an allyltrifluorosilane may afford a rather stable pentacoordinate allylsilicate, which then reacts with an aldehyde via a cyclic six-membered transition state. The high level of regioselectivity of the reaction is presumably due to the enhanced nucleophilicity of the ycarbon of the allylsilicate. 

The chiral Fischer-type chromium carbene complex of furan 28, shown in Scheme 14, participated in nucleophilic 1,4-addition with organolithium reagents followed hy alkylation in a regioselective and diastereoselective manner, creating a quaternary C-3 stereocenter in the 2,3-trisubstituted 2,3-dihydrofuran products after oxidative decom-plexation and reductive cleavage of the chiral auxiliary <2003CEJ5725>. 

Chiral Fischer-type (menthyloxy)(3-furyl)carbene complexes underwent nucleophilic 1,4-addition with lithium reagents in a regioselective and diastereoselective manner. In particular, a reaction with (Z)-2-phenylethenyllithium provided the (Z)-alkene product shown below in excellent %ee <03CEJ5725>. 

The stoichiometric and catalyzed hydroxyamination of norbornene afforded exclusively the exo-cw-diastereomer or 281,82. By contrast, the catalyzed, regioselective and diastereoselective reaction with ( —)-bornene afforded the e t7o-cw-diastereomer 383. 

Complete regioselectivity and diastereoselectivity were obtained on the addition to a trisubsti-tuted double bond, e.g., formation of 1992. 

The highly strained twist" and chair bicyclic trans-cyclooctenes 17 and 18 underwent an exceptionally regioselective and diastereoselective cycloaddition with phenyl azide, the stereochemistry of the dihydrotriazoles was fully retained in the thermal decomposition to aziridi-nes107. Furthermore no imine is produced. 

Activated copper powder or copper(II) acetylacetonate were effective catalysts in the pyrolytic cyclization of 2-azido-3-(2,4-pentadienyl)-l,4-quinones to benzopyrolizines 17 by the presumed intermediacy of a copper(II)-nitrene species which adds to the diene by a radical pathway. Although the yields were generally low, complete regioselectivity and diastereoselectivity (simple and substrate induced) were observed152. 

In chapter 19 we discussed the uses of palladium allyl cation complexes as electrophiles. We established that Pd(0) adds to the opposite face of the allylic system to the leaving group232 to form an t 3 cation complex 233 and that the nucleophile attacks from the opposite face to the Pd so that the two inversions lead to retention. We established that regioselectivity and diastereoselectivity can be well controlled. If this seems unfamiliar we suggest you read the relevant section of chapter 19 before proceeding. 

The reaction with A -acylhydrazones is characterized hy high regioselectivity and diastereoselectivity. ... 

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