Stereochemistry remote control

The simplest nitroalkene, nitroethene, undergoes Lewis acid-promoted [4+2] cycloaddition with chiral vinyl ethers to give cyclic nitronates with high diastereoselectivity. The resulting cyclic nitronates react with deficient alkenes to effect a face-selective [3+2] cycloaddition. A remote acetal center controls the stereochemistry of [3+2] cycloaddition. This strategy is applied to synthesis of the pyrrolizidine alkaloids (+)-macronecine and (+)-petasinecine (Scheme 8.33).165... 

The known preference for transoid elimination of the elements of water from alcohols such as (6-3) controls the stereochemistry of the product. The arrangement in the starting material of the groups about the incipient olefin actually determines the steric identity of the product. The two rotamers of alcohol (6-3) that have the trans hydrogen and hydroxyl shown as their Newman projections (6-3a) and (6-3b) are equally probable since they differ only in the placement of the remote basic ether. The dehydration in fact gives a mixmre of the trans isomer (7-2) and the cis isomer (7-3) presumably from rotamers (6-3a) and (6-3b), respectively. Reaction... 

Burke et al. [84] synthetised nagilactone F (55) by a polyenic cyclization initiated with acetal and concluded with vinylsilane, giving an overall yield of 6%. The key steps in this synthesis were the coupling of substrates 166 and 167 with control of the absolute and relative stereochemistry, the cationic biscyclization to form the intermediate tricyclic trans-anti-trans 169 and the formation of the D ring by regio-selective intramolecular remote functionalization. 

While the process works for a great number of conjugated dienes, a few, such as 1,3-cyclopentadiene and those acyclic dienes that have an oxygen substituenl in an allylic position, did not give a chloroacetoxylation product.23 Control of the 1,4-relative stereochemistry and preparation of compounds analogous to the title compounds also work for acyclic dienes,23 5 This process was used to obtain remote stereocontrol in acyclic systems and applied to the synthesis of a pheromone.5... 

Fuji and co-workers have demonstrated the use of a PPY derivative that utilizes remote stereochemistry and an interesting induced fit process to control selectivity [21]. Upon acylation of catalyst 20, a conformational change occurs, stabilizing the intermediate N-acyliminium ion 21 (Fig. 2a,b). Chemical shifts in the XH NMR and nOes observed support a Jt-Jt interaction between the electron-rich naphthyl ring and the electron-deficient pyridinium ring. This blocks the top face of the catalyst and directs attack of the alcohol from the bottom face. Catalyst 20 effects resolutions of diol-monoesters and amino alcohol derivatives such as 22 and 23 with moderate to good selectivity factors (fcrei=4.7-21, see Fig. 2c) [22]. 

Asymmetric epoxidation, dihydroxylation, aminohydroxylation, and aziridination reactions have been reviewed.62 The use of the Sharpless asymmetric epoxidation method for the desymmetrization of mesa compounds has been reviewed.63 The conformational flexibility of nine-membered ring allylic alcohols results in transepoxide stereochemistry from syn epoxidation using VO(acac)2-hydroperoxide systems in which the hydroxyl group still controls the facial stereoselectivity.64 The stereoselectivity of side-chain epoxidation of a series of 22-hydroxy-A23-sterols with C(19) side-chains incorporating allylic alcohols has been investigated, using m-CPBA or /-BuOOH in the presence of VO(acac)2 or Mo(CO)6-65 The erythro-threo distributions of the products were determined and the effect of substituents on the three positions of the double bond (gem to the OH or cis or trans at the remote carbon) partially rationalized by molecular modelling. 

Tethers (which are usually removable) are used to provide spatial separation between addends in tether-directed remote functionalization. The addends can be identical or different, like the ones represented in Figure 3 as A and RG, where A is the anchor addend that is connected initially and RG is a secondary reactive group that is subsequently added to the fullerene. The tether structure and rigidity controls the regio- and, in the occurrence, stereochemistry of the addition pattern between A and RG. 

The zirconoxycarbene complexes undergo a variety of typical Fischer-carbene reactions. Typically, unsaturated nine-membered zirconoxycarbene complexes such as 103 are readily deprotonated in the a-position to the carbene carbon atom. The stereochemistry of the subsequent alkylation reaction is very efficiently controlled by the remote stereogenic center at C2, resulting in an effective 1,5-asymmetric induction113 (Scheme 34, Fig. 10). 

Diastereoselective macrocycUzation. A ke> step in a synthesis of the 14-membered cembranoid asperdiol (4) involves intramolecular ( yclization of the aldehydo allylic bromide (1) with chromium(II) chloride. The intermolccular version of this reaction is known to be anf/-selective (8,112). Treatment of racemic 1 with CrCl, (5 equiv., THF) results in a 4 1 mixture of the two anti-diastereomers 2 and 3 in 64% combined yield. The stereochemistry of this cyclization is evidently controlled by the remote epoxide group. The natural product was obtained by deprotection of 2 (Na/NH, 51% yield). 

Henbest [ 4] has discussed a variety of reactions where the stereochemistry of the product is apparently controlled or influenced by the electrostatic effects of remote substituents. As an example, the isomer ratio of the steroid alcohols produced by reduction of a 12-keto function is sensitive to both the nature and configuration of a substituent at C(s) (p. 141). We may also cite the conversion of A -3-oxosteroids into their 4,5-epoxy-derivatives by alkaline hydrogen peroxide, where the proportion of /3-epoxy derivatives varies, according to substitution at C(iv>, from ca. 100% in the unsubstituted androst"4-en-3-one to 70% (- - 30% of a-epoxide) in the 17/ -hydroxy derivative. 

The Simmons-Smith cyclopropanation reaction Stereochemically controlled epoxidations Regio- and Stereocontrolled Reactions with Nucleophiles Claisen-Cope rearrangements Stereochemistry in the Claisen-Cope rearrangement The Claisen-Ireland rearrangement Pd-catalysed reactions of allylic alcohols Pd-allyl acetate complexes Stereochemistry of Pd-allyl cation complexes Pd and monoepoxides of dienes The control of remote chirality Recent developments Summary... 

The migrating group passes suprafacially across the Z-alkene but appears to invert because the skeleton must be redrawn to show the T -al kcnc. This is an elegant way of transforming relatively easy to control 1,2 stereochemistry into more remote 1,4 stereochemistry.16 There is another example of the conversion of 1,2- into 1,4-stereochemistry at the end of this chapter. Not everyone is happy with stoichiometric toxic tin, but an alternative is available in the silicon compounds such as 101... 

The syn selectivity is controlled by the double bond geometry of the trans enolate 272 whereas the more remote aspects of the stereocontrol are controlled by the molecules themselves. Just a note at this point we normally associate trans enolates with anti aldol products -the product observed is called syn only because of the way it is drawn, there is nothing unusual here 275. The chiral centres in the enolate 272 are too remote to be effective and it is those in the aldehyde 273 that control the more remote aspects of stereochemistry. If we want to explain this selectivity, we need to have a reason for why one diastereotopic face of the aldehyde is attacked and not the other. As might be expected, the aldehyde reacts with Felkin-Anh selectivity as described earlier in this chapter. 

Anti stereochemistry in six-membered rings Conformational control from a chiral centre in the cyclohexenone Remote stereochemical control in five-membered rings prostaglandins Regio- and stereochemical control in open chain compounds Asymmetric induction by a chiral auxiliary on the enolate Tandem Michael-Michael Reactions One Conjugate Addition Follows Another Double Michael or Diels-Alder reaction ... 

The presence of the Fe(CO)3 group also permits reactions with nucleophiles to be carried out at the diene functionality with control of the stereochemistry, the nucleophile being able to attack only on the side of the coordinated diene remote from the metal centre. The organic ligand can be removed in the final step of the reaction. ... 

Obviously, catalyst structure is the key to determining enantiocontrol in the phospho-aldol reaction. In the lanthanide heterobimetaUic systems, backbone chirality within the binaphthol leads to generation of a stereocentre at the metal itself and does so with complete diastereospecificity. This is yet another example of the concept of chirality tra s/er, wherein fixed stereochemistry at one site leads to control over stereochemistry at a more remote site and is one of the most powerful concepts in catalyst design. It is the presence of such a highly... 

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