Stereochemistry acyclic

It is possible to prepare 1-acetoxy-4-chloro-2-alkenes from conjugated dienes with high selectivity. In the presence of stoichiometric amounts of LiOAc and LiCl, l-acetoxy-4-chloro-2-hutene (358) is obtained from butadiene[307], and cw-l-acetoxy-4-chloro-2-cyclohexene (360) is obtained from 1.3-cyclohexa-diene with 99% selectivity[308]. Neither the 1.4-dichloride nor 1.4-diacetate is formed. Good stereocontrol is also observed with acyclic diene.s[309]. The chloride and acetoxy groups have different reactivities. The Pd-catalyzed selective displacement of the chloride in 358 with diethylamine gives 359 without attacking allylic acetate, and the chloride in 360 is displaced with malonate with retention of the stereochemistry to give 361, while the uncatalyzed reaction affords the inversion product 362. 

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-... 

The stereochemistry of both chlorination and bromination of several cyclic and acyclic dienes has been determined. The results show that bromination is often stereo-specifically anti for the 1,2-addition process, whereas syn addition is preferred for 1,4-addition. Comparable results for chlorination show much less stereospeciftcity. It appears that chlorination proceeds primarily through ion-pair intermediates, whereas in bromina-hon a stereospecific anfi-l,2-addition may compete with a process involving a carbocation mtermediate. The latter can presumably give syn or anti product. 

Table 6.8. Stereochemistry of E2 Eliminations for Some Acyclic Substrates...

The stereochemistry of radical addition of hydrogen bromide to alkenes has been studied with both acyclic and cyclic alkenes. Anti addition is favored.This is contrary to what would be expected if the s[p- carbon of the radical were rapidly rotating or inverting with respect to the remainder of the molecule ... 

The photocyclization of N-aryl enamines derived from cyclic or acyclic ketones proceeds under mild conditions to produce 2,3-dihydroindole derivatives (178b). The stereochemistry of the products is predominantly trans, which follows from a photochemical electrocyclic process which should take place in a conrotatory manner (178c,I78d). However, the presence of some cis products is not as easily explained. 

The synthetic challenge is now reduced to the preparation of intermediates 2-4. Although intermediates 3 and 4 could potentially be derived in short order from very simple precursors (see Scheme 4), intermediate 2 is rather complex, particularly with respect to stereochemistry. Through a short sequence of conventional functional group manipulations, it is conceivable that aldehyde 2 could be derived from intermediate 9. Hydrolysis and keta-lization reactions could then permit the formation of 9 from intermediate 11, the cyclic hemiaminal of the highly stereo-defined acyclic molecule, intermediate 12. 

Photolysis of (Z)-3-phenyl-2-(2-phenylvinyl)-2//-azirine (1) in benzene solution yields 1-phenyl-3//-2-benzazepine (2) in excellent yield.39 However, the stereochemistry of the alkenyl side chain and the solvent used are important in determining the outcome of the reaction. For example, the E-isomer of the 2//-azirine 1 on photolysis in benzene solution yields 2,3-diphenyl-pyrrole as the major product (85 %) the pyrrole is also obtained on heating the Z- or E-isomer in benzene solution. In contrast, irradiation of the Z-isomer in methanol yields only acyclic products. 

The reactions of allylboronates 1 (R = H or CH3) may proceed either by way of transition state 3, in which the a-substituent X adopts an axial position, or 4 in which X occupies an equatorial position. These two pathways are easily distinguished since 3 provides 7 with a Z-olefin, whereas 4 provides 8 with an E-olefinic linkage. There is also a second fundamental stereochemical difference between these two transition states 7 and 8 are heterochirally related from reactions in which 1 is not racemic. That is, 7 and 8 arc enantiomers once the stereochemistry-associated with the double bond is destroyed. Thus, the selectivity for reaction by way of 3 in preference to 4, or via 6 in preference to 5 in reactions of a-subsliluted (Z)-2-butenylboronate 2, is an important factor that determines the suitability of these reagents for applications in enantioselective or acyclic diastereoselective synthesis. 

Experimentally, there are two approaches to the elucidation of the structure of vinyl cations first, preparation and solvolysis of systems where because of geometric restrictions the intermediate vinyl cation by necessity is bent and second, by a careful examination of the stereochemistry of solvolysis of appropriate acyclic substrates. 

More mechanistic work undoubtedly will be done on the stereochemistry of solvolysis, particularly of simple alkyl-substituted acyclic vinyl systems. The questions of concerted anchimerically assisted or nonconcerted rearrangements both to the double bond and across the double bond need further development. 

In acyclic systems, the stereochemistry of alkylation depends on steric factors. Stereoselectivity is low for small substituents.71... 

Enantioselectivity can also be based on structural features present in the reactants. A silyl substituent has been used to control stereochemistry in both cyclic and acyclic systems. The silyl substituent can then be removed by TBAF.326 As with enolate alkylation (see p. 32), the steric effect of the silyl substituent directs the approach of the acceptor to the opposite face. 

The participation of sulfoxy groups can be used to control the stereochemistry in acyclic systems. In the reaction shown below, the internal sulfoxide captures the bromonium ion and then undergoes inversion at sulfur in the hydrolytic step. 

Acyclic Ketones. The stereochemistry of the reduction of acyclic aldehydes and ketones is a function of the substitution on the adjacent carbon atom and can be predicted on the basis of the Felkin conformational model of the TS,63 which is based on a combination of steric and stereoelectronic effects. 

The stereochemistry of acyclic anionic oxy-Cope rearrangements is consistent with a chair TS having a conformation that favors equatorial placement of both alkyl and oxy substituents and minimizes the number of 1,3-diaxial interactions.214 For the reactions shown below, the double-bond configuration is correctly predicted on the basis of the most stable TS available in the first three reactions. In the fourth reaction, the TSs are of comparable energy and a 2 1 mixture of E- and Z-isomers is formed. 

The mechanism and stereochemistry of the orthoester Claisen rearrangement is analogous to the Cope rearrangement. The reaction is stereospecific with respect to the double bond present in the initial allylic alcohol. In acyclic molecules, the stereochemistry of the product can usually be predicted on the basis of a chairlike TS.233 When steric effects or ring geometry preclude a chairlike structure, the reaction can proceed through a boatlike TS.234... 

If HMPA is included in the solvent, the Z-enolate predominates.236,238 DMPU also favors the Z-enolate. The switch to the Z-enolate with HMPA or DMPU is attributed to a looser, perhaps acyclic TS being favored as the result of strong solvation of the lithium ion. The steric factors favoring the -TS are therefore diminished.239 These general principles of solvent control of enolate stereochemistry are applicable to other systems.240 For example, by changing the conditions for silyl ketene acetal formation, the diastereomeric compounds 17a and 17b can be converted to the same product with high diastereoselectivity.241... 

The predictable regio- and stereochemistry make these reactions valuable in establishing stereochemistry in both acyclic and cyclic systems. 

Although the allylation reaction is formally analogous to the addition of allylic boranes to carbonyl derivatives, it does not normally occur through a cyclic TS. This is because, in contrast to the boranes, the silicon in allylic silanes has little Lewis acid character and does not coordinate at the carbonyl oxygen. The stereochemistry of addition of allylic silanes to carbonyl compounds is consistent with an acyclic TS. The -stereoisomer of 2-butenyl(trimethyl)silane gives nearly exclusively the product in... 

Fragmentation reactions can also be used to establish stereochemistry of acyclic systems based on stereochemical relationships built into cyclic reactants. In both the examples shown below, the aldehyde group generated by fragmentation was reduced in situ. 

The synthesis of Baccatin HI shown in Scheme 13.57, which was completed by a group led by the Japanese chemist Teruaki Mukaiyama, takes a different approach for the previous syntheses. Much of the stereochemistry was built into the B-ring by a series of acyclic aldol additions in Steps A through D. A silyl ketene acetal derivative... 

Arguably the most challenging aspect for the preparation of 1 was construction of the unsymmetrically substituted sec-sec chiral bis(trifluoromethyl)benzylic ether functionality with careful control of the relative and absolute stereochemistry [21], The original chemistry route to ether intermediate 18 involved an unselective etherification of chiral alcohol 10 with racemic imidate 17 and separation of a nearly 1 1 mixture of diastereomers, as shown in Scheme 7.3. Carbon-oxygen single bond forming reactions leading directly to chiral acyclic sec-sec ethers are particularly rare since known reactions are typically nonstereospecific. While notable exceptions have surfaced [22], each method provides ethers with particular substitution patterns which are not broadly applicable. 

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