Bonds stereoselective formation

Cyclopentene derivatives with carboxylic acid side-chains can be stereoselectively hydroxy-lated by the iodolactonization procedure (E.J. Corey, 1969, 1970). To the trisubstituted cyclopentene described on p. 210 a large iodine cation is added stereoselectively to the less hindered -side of the 9,10 double bond. Lactone formation occurs on the intermediate iod-onium ion specifically at C-9ot. Later the iodine is reductively removed with tri-n-butyltin hydride. The cyclopentane ring now bears all oxygen and carbon substituents in the right stereochemistry, and the carbon chains can be built starting from the C-8 and C-12 substit""" ... 

Several cortisone derivatives with glucocorticoid effects are most active, if they contain fluorine in the 9or-position together with an Il(9-OH group. Both substituents are introduced by the cleavage of a 9,11 -epoxide with hydrogen fluoride. The regio- and stereoselective formation of the -epoxide is achieved by bromohydrination of a 9,11-double bond and subsequent alkali treatment (J. Fried, 1954). 

The Pd-catalyzed hydrogenolysis of vinyloxiranes with formate affords homoallyl alcohols, rather than allylic alcohols regioselectively. The reaction is stereospecific and proceeds by inversion of the stereochemistry of the C—O bond[394,395]. The stereochemistry of the products is controlled by the geometry of the alkene group in vinyloxiranes. The stereoselective formation of stereoisomers of the syn hydroxy group in 630 and the ami in 632 from the ( )-epoxide 629 and the (Z)-epoxide 631 respectively is an example. 

Treatment of an epimeric mixture of 4-substituted 2-(trimethylsilyloxy)-5-phenyl-3-phenylthio-l,4-oxazine 264 with ZnBr2 led to the stereoselective formation of perhydropyrido[2,l-c][l,4]oxazine 266 via the iminium ion 265 by the phenyl bearing stereocenter directed addition of the olefinic double bond from the /S-face of the cyclic moiety (97SL799, 98T10309). Similarly, an epimeric mixture of (45,9aS)-l-trimethylsilyloxy-4-phenyl-3,4,6,7-tetra-hydropyrido[2,l-c][l,4]oxazine was prepared by cyclization of (Z)-5(S)-phenyl-3-phenvlsulfanyl-2-trimethylsilyloxy-4-[4-(trimethylsilyl)but-3-enyll morpholine (OOSC2565). 

However, a number of examples have been found where addition of bromine is not stereospecifically anti. For example, the addition of Bf2 to cis- and trans-l-phenylpropenes in CCI4 was nonstereospecific." Furthermore, the stereospecificity of bromine addition to stilbene depends on the dielectric constant of the solvent. In solvents of low dielectric constant, the addition was 90-100% anti, but with an increase in dielectric constant, the reaction became less stereospecific, until, at a dielectric constant of 35, the addition was completely nonstereospecific.Likewise in the case of triple bonds, stereoselective anti addition was found in bromination of 3-hexyne, but both cis and trans products were obtained in bromination of phenylacetylene. These results indicate that a bromonium ion is not formed where the open cation can be stabilized in other ways (e.g., addition of Br+ to 1 -phenylpropene gives the ion PhC HCHBrCH3, which is a relatively stable benzylic cation) and that there is probably a spectrum of mechanisms between complete bromonium ion (2, no rotation) formation and completely open-cation (1, free rotation) formation, with partially bridged bromonium ions (3, restricted rotation) in between. We have previously seen cases (e.g., p. 415) where cations require more stabilization from outside sources as they become intrinsically less stable themselves. Further evidence for the open cation mechanism where aryl stabilization is present was reported in an isotope effect study of addition of Br2 to ArCH=CHCHAr (Ar = p-nitrophenyl, Ar = p-tolyl). The C isotope effect for one of the double bond carbons (the one closer to the NO2 group) was considerably larger than for the other one. ... 

As shown earlier in many examples, the Claisen rearrangement of allyl vinyl ethers also provides a very powerful method for carbon-carbon bond formation in domino processes. Usually, the necessary ethers are formed in a separate step. However, both steps can be combined in a novel domino reaction developed by Buchwald and Nordmann [306]. This starts from an allylic alcohol 6/4-102 and a vinyl iodide 6/4-103, using copper iodide in the presence of the ligand 6/4-104 at 120 °C to give 6/4-105 (Scheme 6/4.25). The reaction even allows the stereoselective formation of two adjacent quaternary stereogenic centers in high yield. 

When the TMS group is absent and if the reaction is carried out in methanol, a platinum(ll)-catalyzed alkoxycy-clization takes place (Scheme 87).308 This cyclization catalyzed by Pt(ll) was found to be mechanistically similar to the carbohydroxypalladation reported by Genet.309 310 This process has intrinsic importance in organic synthesis since it allows the simultaneous and generally stereoselective formation of a C-O and a C-C bond to occur from an enyne system. This reaction has been applied for the synthesis of a key intermediate of podophyllotoxin.311... 

Since the 1960s the syndiospecific chain-end controlled polymerization of propene in the presence of homogeneous vanadium-based catalytic systems has been known. For these systems, it has been well established by the work of Zambelli and co-workers that the polymerization is poorly regioselective and the stereoselective (and possibly syndiospecific) step is propene insertion into the metal secondary carbon bond with formation of a new secondary metal-carbon bond.133134... 

An interesting pericyclic-anionic-pericyclic domino reaction showing a high stereoselectivity is the cycloaddition-aldol-retro-ene process depicted in scheme 20.1581 The procedure presumably starts with a [4+2]-cycloaddition of diene 98 and S02 in presence of a Lewis acid. After opening of the formed adduct reaction with (Z)-silyl vinyl ether 99 leads to a mixture of alk-2-enesulfinic acids 101. It follows a retro-ene reaction which affords a 7 3 mixture of the products 102 and 103. The reaction described by Vogel et al is a nice example for the efficient generation of polypropionate chains with the stereoselective formation of three stereogenic centers and one (0-double bond in a three-component domino reaction in its strict definition. 

Thus, fluorination of 1,3-dienes proceeds through an allylic ion, while weakly bridged halonium ions are the intermediates in chlorination and bromination of dienes (vide infra). Furthermore, starting from the experimental evidence that 13 is produced under kinetic conditions and not from subsequent rearrangement of the 1,2- and 1,4-adducts, the authors suggested that 13 arose from rearrangement of the allyl cation intermediate, 17. Consistent with an open ion pair intermediate is also the stereoselective formation of the threo isomer from both 1,3-pentadienes, as well as the preference for the addition to the 1,2-bond observed in the reaction of both isomeric pentadienes. This selectivity may indeed... 

Cp=Cy bond of indenyl-allenylidene complexes 30 which leads to the stereoselective formation of cationic amino-allenylidenes 31. When R = Ph, complexes 31 can be transformed into the secondary derivatives 32 via treatment with LiBHEts and subsequent purification on sUica-gel column. Further insertions of MeC=CNEt2 into 32 allow the preparation of polyunsaturated cumulene chains (related insertion reactions will be discussed in the reactivity section). 

Numerous studies have been directed toward expanding the chemistry of the donor/ac-ceptor-substituted carbenoids to reactions that form new carbon-heteroatom bonds. It is well established that traditional carbenoids will react with heteroatoms to form ylide intermediates [5]. Similar reactions are possible in the rhodium-catalyzed reactions of methyl phenyldiazoacetate (Scheme 14.20). Several examples of O-H insertions to form ethers 158 [109, 110] and S-H insertions to form thioethers 159 [111] have been reported, while reactions with aldehydes and imines lead to the stereoselective formation of epoxides 160 [112, 113] and aziridines 161 [113]. The use of chiral catalysts and pantolactone as a chiral auxiliary has been explored in many of these reactions but overall the results have been rather moderate. Presumably after ylide formation, the rhodium complex disengages before product formation, causing degradation of any initial asymmetric induction. 

Having generated suitable (partially) cationic, Lewis acidic metal centers, several factors need to be considered to understand the progress of the alkene polymerisation reaction the coordination of the monomer, and the role (if any) of the counteranion on catalyst activity and, possibly, on the stereoselectivity of monomer enchainment. Since in d° metal systems there is no back-bonding, the formation of alkene complexes relies entirely on the rather weak donor properties of these ligands. In catalytic systems complexes of the type [L2M(R) (alkene)] cannot be detected and constitute structures more closely related to the transition state rather than intermediates or resting states. Information about metal-alkene interactions, bond distances and energetics comes from model studies and a combination of spectroscopic and kinetic techniques. 

For glycopeptide synthesis, much attention has to be paid to the stereoselective formation of the natural-type glycosidic bond which must remain unchanged in the course of the synthesis. Therefore, in comparison to peptide synthesis, the compatibility and chemoselectivity of the applied reaction is fundamental in glycopeptide synthesis. 

The reaction of a prostereogenic, nucleophilic substrate (carbanion) with a reagent R1—X, containing an achiral electrophilic part R1 and a chiral nucleofugal leaving group X (PAC/ NEN-reaction) leads within an SN2 reaction to the stereoselective formation of C -C bonds 2 ... 

When the terminal acetylenic group was replaced with an olefinic double bond the analogous process gave rise to the stereoselective formation of di-hydropyrido[l,2- ]azepines 98 in a good yield (Scheme 30) (97T14687). 

A more stereoselective formation of the glycosidic bond, assuming nonequilibrium conditions for the polycondensation, involves the use of a large counter-ion (Ae). 4 The intermediate carbonium ion (7) would be stabilized preferentially from the least hindered side of the ring as in (8) and, consequently, would furnish one glycoside anomer such as (9) (see Section... 

Trialkyltin hydrides can serve as chain carriers in radical reactions. The low Sn-H bond energy (74 kcal/mol) facilitates easy homolytic cleavage by an initiator radical to produce tin radicals that are in a position Lo cleave a Cl-C bond with formation of a carbon radical. The resulting carbon radical cycli/es stereoselectively to pyrurt 6 in a b-exo-trig ring closure. ... 

Stereoselective formation of the glycosidic bond can be achieved by this procedure. The dibutylstannylene complex of 3,4,6-tri-O-benzyl-D-mannose was converted into benzyl 3,4,6-tri-0-benzyl-f3-D-mannopyranoside, useful intermediate for the synthesis of 2-deoxy-2-[18F]fluoro-D-glucose [138]. 

The phyllocladane skeleton 131 was constructed efficiently by stereoselective formations of six carbon-carbon bonds and four rings via a one-pot sequence of cyclizations the ene type, [2+2+2], and [4+2] cycloadditions. In this synthesis, the Conia ene reaction of 127 takes place under mild conditions to generate 128, and the cyclotrimerization of its diyne with 118 gives 129. These two reactions are catalysed by CpCo(CO)2. Finally, ring-opening to give 130 and intramolecular Diels-Alder reaction in the presence of DPPE produced the phyllocladane skeleton 131 in a total yield of 42% [55]. 

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