Retention of stereochemistry

Zinc acetylides, prepared in situ by the treatment of lithium acetylides with ZnCF, are widely used. The zinc acetylide 311, prepared in situ, reacts with (Z)-3-iodo-2-buten-l-ol (312) with nearly complete retention of stereochemistry to afford an important intermediate 313 for carotenoid synthesis[227]. 

The formation of g-alkyl-a,g-unsaturated esters by reaction of lithium dialkylcuprates or Grignard reagents in the presence of copper(I) iodide, with g-phenylthio-, > g-acetoxy-g-chloro-, and g-phosphoryloxy-a,g-unsaturated esters has been reported. The principal advantage of the enol phosphate method is the ease and efficiency with which these compounds may be prepared from g-keto esters. A wide variety of cyclic and acyclic g-alkyl-a,g-unsaturated esters has been synthesized from the corresponding g-keto esters. However, the method is limited to primary dialkylcuprates. Acyclic g-keto esters afford (Zl-enol phosphates which undergo stereoselective substitution with lithium dialkylcuprates with predominant retention of stereochemistry (usually > 85-98i )). It is essential that the cuprate coupling reaction of the acyclic enol phosphates be carried out at lower temperatures (-47 to -9a°C) to achieve high stereoselectivity. When combined with they-... 

Further evidence for a bromine-bridged radical comes from radical substitution of optically active 2-bromobutane. Most of the 2,3-dibromobutane which is formed is racemic, indicating that the stereogenic center is involved in the reaction. A bridged intermediate that can react at either carbon can explain the racemization. When the 3-deuterated reagent is used, it can be shown that the hydrogen (or deuterium) that is abstracted is replaced by bromine with retention of stereochemistry These results are also consistent with a bridged bromine radical. 

Other sulfonate derivatives are obtained by the use of trifluoromethanesulfonyl hypochlorite and hypobromite (CF3SO2OQ and CF3S020Br) in reactions with petfluoroalkyl halides and their derivatives [30. These reactions lead to the corresponding trifluoromethanesulfonate derivatives of alkanes (equation 28) (Table 11). The reaction proceeds with complete retention of stereochemistry at the carbon center [30]. 

Advantages of the Stille reaction include neutral conditions under which the reaction takes place, often with full retention of stereochemistry, and compatibility with nearly all functional groups thus eliminating additional steps required for protection and deprotection. Conversely, a highly undesirable drawback is the use of toxic tin compounds and the ensuing difficult removal of these from the reaction mixture. 

Ion pair (Section 11.5) A loose complex between two ions in solution. Ion pairs are implicated as intermediates in S l reactions to account for the partial retention of stereochemistry that is often observed. 

The intermediate vinyl copper species react readily with a variety of electrophiles, with retention of stereochemistry. 

Note. For oxidative cleavage, with retention of stereochemistry, of such species, see Chapter 9. 

Reactions of cyclopentyne with alkenes gives [2+2] cycloadduct with complete retention of stereochemistry (Scheme 24) [120], Laird and Gilbert observed the expected [2+2] cycloadduct along with the polycyclic adduct in the reaction of norbomyne with 2,3-dihydropyran (Scheme 24) [121], and located a cyclopropyl-carbene intermediate [122],... 

Diels-Alder reaction is one of the most fundamental reactions for organic synthesis. Its synthetic utility is unquestioned. The stereochemistry of the reactions has attracted much attention. The retention of stereochemistry in the diene and the dienophile, the predominant formation of endo-attack products in the reactions of cyclic dienes, and highly controlled regioselectivity in the reactions of substimted dienes and... 

Recently, the scope of the allylic substitution has been extended to sulfinate salts 84 to obtain allylic sulfones 85. Due to solubility problems of both nucleophile 84 and carbonate leaving group, a polar solvent mixture of DMF and 2-methoxyethanol had to be employed, which limits the reaction to the use of a phosphine ligand. Thus, various aryl sulfinates 84 and functionalized carbonates 81 could be converted to the corresponding allylic sulfones 85 with good to excellent yields and regioselectivites and complete retention of stereochemistry (eq. 2 in Scheme 20) [65]. 

Since work with the radical clock substrate probes indicated important differences in the hydroxylation mechanisms for M. capsulatus (Bath) and M. trickosporium OB3b, work with (R) and (S)-[1-2H,1-3H]ethane with both enzymes was carried out (93, 94). With M. tri-chosporium OB3b, approximately 65% of the product displays retention of stereochemistry (93). A rebound rate constant of 2 - 6 x 1012 s-1 was calculated, assuming a free energy change of 0.5 kcal mole-1 for rotation about the C-C bond (94). This estimate approaches the value obtained from the radical clock substrate probe analysis (59). 

In recent years, cross-coupling methodology has emerged as a viable tool for enamide synthesis, and, indeed, there are a number of published protocols which employ palladium- or copper-catalyzed stereospecific amidations of vinyl halides [17]. For example, Buchwald and coworkers had recently shown that a copper-catalyzed cross-coupling of vinyl bromides or iodides proceeded with retention of stereochemistry (Scheme 9.16), though the only example using a tetrasubstituted vinyl halide, 23, lacked the need for any stereochemical control in the halide portion [18]. Based on this it seemed feasible that the desired enamide 22 could potentially be assembled via a comparable coupling between amide 24 and a stere-odefined vinyl halide such as 25. 

Oximinoimidazolides can be obtained from oximes and CDI with retention of stereochemistry heating in octane or nonane under anhydrous conditions leads to their conversion to imidazolylimidates [123]... 

A Lewis acid-induced aza-Diels-Alder reaction between the /3-lactam-imine 295 and 3,4-di hydro-2//-pyran gives the two diastereomeric pyranoquinolines 296 and 297. Under basic conditions, these products rearrange to the amino-substituted pyranoindolizinones, 298 and 299, respectively, with retention of stereochemistry (Scheme 74) <2003CEJ3415>. 

The current procedure starts with the ester, ethyl 1-naphthoate, and converts it into homologated product in 81% yield without isolation of any intermediates. Safe, commercially available materials are employed. Based on a recently published variation43 of our original homologation methods,4 1 It represents a general procedure applicable to esters 1 bearing aryl, alkenyl, alkynyl and primary, secondary or tertiary alkyl attachments R. Yields range from 67-90% (on a 25-mmol scale) and like the Arndt-Eistert sequence this procedure affords retention of stereochemistry for the... 

A remaining point to interpret is the complete retention of stereochemistry in the cyclobutane products. Models that have previously been proposed for excited diene triplets 80>, 15 and 16, have a full bond between atom 2 and 3 of the diene, and cannot adequately represent the triplet dienes formed in this reaction. A great deal of double bond character at the terminal bonds is required to prevent rotation. This... 

Hydrogermylations by these hydrides were found to proceed with retention of stereochemistry at Ge (equation 14)32. 

The first chiral a-oxygenated stannanes were prepared by Still59. Addition of Bu3SnLi to a-methy l-/J-phenylpropionaldehyde followed by MOMC1 led to a separable 1 1 mixture of syn and anti alkoxy stannanes (Scheme 26). Lithiation with n-BuLi and addition of acetone gave the respective adducts with overall retention of stereochemistry. Thus, it is implied that the intermediate a-alkoxy lithio derivatives retain their configuration. 

Addition of Bu3SnLi or McsSnI.i to 4-t-butylcyclohexanone affords mixtures of trans and cis adducts in ratios that depend on reaction conditions (Table ll)68. In THF, a 93 7 mixture is obtained with both reagents. This ratio is thought to represent the thermodynamic distribution—the axial stannane being favored. In ether, the cis isomer predominates, suggesting a kinetic preference for equatorial addition. Each of the two isomers can be lithiated with BuLi. Subsequent treatment with alkyl halides or carbonyl compounds affords the substituted alkoxy cyclohexanes with retention of stereochemistry. 

Step 1 is fundamentally an SN2 reaction (kinetics related to structural variations of the reactants,16 8 retention of stereochemistry at phosphorus912), except in those instances wherein a particularly stable carbocation is produced from the haloalkane component.13 A critical experiment concerned with verification of the Sn2 character of Step 1 by inversion of configuration at the carbon from which the leaving group is displaced was inconclusive because elimination rather than substitution occurred with the chiral secondary haloalkane used.14 An alternative experiment suggested by us in our prior review using a chiral primary substrate apparently has not yet been performed.2... 

The species identified as XA reacts with styrene to give the expected cyclopropane. The rate constant for this reaction is ca 200 times less than the corresponding rate constant for 3BA (Table 6). Also, use of the deuterium-labeled a-methylstyrene reveals that the cyclopropanation occurs with essentially total retention of stereochemistry. Moreover, precisely the same result is obtained when this carbene is formed by triplet sensitization rather than by direct irradiation. These findings also point to a reaction originating from a singlet carbene. 

As expected, DMFL reacts with styrene to give the appropriate cyclopropane. Irradiation of the diazo-compound in benzene containing the labeled a-methylstyrene gives cyclopropane with essentially complete retention of stereochemistry (Table 6). 

Insertion of palladium into the Si-Sn bond generates intermediate 428 that undergoes m-addition on the triple bond (Scheme 108). The resulting vinylpalladium 429 ensures the carbopalladation of the second triple bond followed by reductive elimination with retention of stereochemistry.376... 

The silastannation products serve as useful building blocks. Treatment of (Z)-a-stannyl-/3-silylstyrenes with HG1 in the presence of Et4NGl results in protodestannation with retention of stereochemistry to give the corresponding CE)-/ -silylstyrenes in high yield (Equation (108)).254... 

In the envisaged titanium oxo complex, the Ti atom is side-bound to the peroxy moiety (02H), consistent with all the spectroscopic results mentioned in Section III in Scheme 27, between the two O atoms that are side-bound to Ti4+, the O atom attached to both the Ti and H atoms is expected to be more electrophilic than the O atom attached to only the Ti atom and is likely to be the site of nucleophilic attack by the alkene double bond. The formation of the Ti-OH group (and not the titanyl, Ti=0, as proposed by Khouw et al. (221)) after the epoxidation and its subsequent condensation with Si-OH to regenerate the Ti-O-Si links had been observed (Section III.B) by FTIR spectroscopy by Lin and Frei (133). Because this is a concerted heterolytic cleavage of the 0-0 bond, high epoxide selectivity and retention of stereochemistry may be expected, as indeed has been observed experimentally (204). 

Reduction of vinyloxiranes The substrates are reduced rapidly by Sml2 to (E)-allylic alcohols without effect on keto, ester, or nitrile groups. Chiral substrates are reduced to optically active alcohols with complete retention of stereochemistry. 

The tin-lithium exchange reactions are thought to proceed with retention of stereochemistry. However, as the stannanes employed in this study were racemic, there is no evidence in support of this pathway. 

The stereochemistry of the process was examined by analysis of the products resulting from trapping the lithioallene from a chiral allenylcarbamate with Me3SiCl (Eq. 9.11). Sequential lithiation with BuLi followed by addition of Me3SiCl at -78°C afforded a 75 25 mixture of the syn and anti adducts in 70% yield. On the other hand, deprotonation with LDA at -78 °C in the presence of excess Me3SiCl gave rise to the syn adduct as the sole product in 70% yield. It could therefore be surmised that (1) lithiation proceeds with retention of stereochemistry and (2) syn/anti isomerization of the putative allenyllithium intermediate at -78 °C is slower than silyla-tion (Eq. 9.12). 

Thermally, ammine complexes of chromium(III) containing a coordinated ligand X (where X is CL, CNS , etc.) undergo substitution of X by H20 in aqueous solution with retention of stereochemistry ... 

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