Alkene double asymmetric induction

The alternative approach, in which a chiral hydroborating agent is utilized, is more flexible in that there is no requirement for asymmetry in the alkene. However, if such asymmetry should be present of necessity, then there is the possibility of utilizing the principles of double asymmetric induction by correct choice of chiral reagent. - 8 Little work has been done in this field as yet and it will not be discussed further. 

A further double asymmetric induction example is given by the alkene IS, derived from a-methylserine (Scheme 3.14). Reaction with the AD-mix [3 was the mismatched system while AD-mix a gave good stereoselection for the syn-diol [310],... 

Conformational considerations restrict the number of possible transition state geometries in intramolecular cyclopropanations, which are quite selective, as shown by the examples from Doyle, Martin, and Muller illustrated in Scheme 6.38a [140,141]. Intramolecular cyclopropanation of diazo esters of chiral allylic alcohols are subject to double asymmetric induction, as shown by the series of examples in Scheme 6.38b. For all of these substrates, the exo product is slightly preferred when cyclopropanation is mediated by an achiral catalyst [142], but this selectivity is reversed dramatically when the S ester is allowed to react with the 5-S-MEPY catalyst. This pronounced endo selectivity persists for both the E and the Z-alkenes, although it is higher for the Z alkenes. Note also that when the chirality sense of the substrate and the catalyst are mismatched (5 substrate and R catalyst), the endo selectivities are low, unless R1/R2 are trimethylsilyl. For the matched case of double asymmetric induction, the same features that cause the endo selectivity can be used... 

Hydro qrlation of the E-alkene (1) by use of catalytic osmium tetroxlde led to the L-arabino-product (2) In an 8 1 preponderance over the L-xylo isomer (Scheme 1), in accordance with the KishI rule. Other workers have carried out similar reactions with other y-alkoxy-o,p-unsaturated esters of E-configuration using stoichiometric osmium tetroxide in the presence of chiral amines to give double asymmetric induction Z-Isomers gave very low diastereoselectlvity.3... 

Recently, by selection of the appropriate enantiomer of the chiral HWE reagent 31a, the concept of double asymmetric induction in an asymmetric carbonyl olefi-nation step has been applied in controlling the geometry of the alkenic intermediate 103 in the total synthesis of structurally complex macrolides [68, 69] vide infra). 

In the case of tri-substituted alkenes, the 1,3-syn products are formed in moderate to high diastereoselectivities (Table 21.10, entries 6—12). The stereochemistry of hydrogenation of homoallylic alcohols with a trisubstituted olefin unit is governed by the stereochemistry of the homoallylic hydroxy group, the stereogenic center at the allyl position, and the geometry of the double bond (Scheme 21.4). In entries 8 to 10 of Table 21.10, the product of 1,3-syn structure is formed in more than 90% d.e. with a cationic rhodium catalyst. The stereochemistry of the products in entries 10 to 12 shows that it is the stereogenic center at the allylic position which dictates the sense of asymmetric induction... 

As pointed out in the introduction, a particular feature of hydrosilylation reactions is that they require catalysis. Arguably the most valuable of enantioselective synthetic methods are those in which asymmetric induction occurs from small quantities of enantiomerically pure catalysts. It is natural, therefore, that considerable effort has been directed towards the catalytic enantioselective hydrosilylation-oxidation of C —C double bonds. Some degree of success has been met in the hydrosilylation of simple alkenes and 1,3-dienes, and in intramolecular hydrosilyla-tions. Also, as discussed at end of this section, a catalytic enantioselective disilylation (effectively the same as a hydrosilylation) has been developed for a,)3-unsaturated ketones. 

The halocyclization of 1 -benzyloxy-3-hydroxy-4-alkenes or l-benzyloxy-3-alkoxy-4-alkenes, carried out with iodine in tetrahydrofuran, in the presence of sodium hydrogen carbonate, or with bromine in dichloromethane, gives tetrahydrofurans in good yield. 1,2-Asymmetric induction is very effective and m-2.3-disubstituted tetrahydrofurans are the major products, in analogy with the cyclization of the corresponding diols, unless the double bond has Z configuration16,25. 

High to total 1,2-asymmetric induction was observed in the iodocyclization of IV-alkoxy-3-sub-stituted 4-alkenylamines, the cyclic products 1 have predominantly the 2,3-trans relationship. When the C-3 substituent is a methyl group, the induced diastereoselectivity also depends on the substitution pattern of the alkene, e.g., changing the toaZ double bond, dramatically increases the trans/cis ratio from 67 33 to 100 0. Diastereomeric ratios were determined by H NMR and chromatographic purification of individual diastereomers77. 

An interesting intramolecular variation of this reaction provides oxazolidones, which may be hydrolyzed to synthetically useful optically active 2-amino-3-butenols (eq 8). The absolute stereochemistry of the stereocenter formed is dependent upon the geometry about the double bond of the 2-butenylene dicarbamate substrate. A related Pd -promoted [3 + 2] cycloaddition of an activated alkene with a 2-(sulfonylmethyl)-2-propenyl carbonate, using the bis(hydroxyalkyl)-substituted ligand (8), gave methylenecyclopentane derivatives with high asymmetric induction. ... 

Other chirally modified platinum, cobalt and rhodium complexes give lower inductions, although sometimes with higher aldehyde and branched product yields (Table 1). A strong dependance of chemo-, regio- and stereoselectivity on reaction conditions and conversion rates is observed, sometimes with contradictory results. Attempts to optimize the chemo- and re-gioselectivity usually lead to lower asymmetric inductions. Moreover, since double-bond isomerization and racemization take place under hydroformylation conditions, the results reported do not necessarily reflect the primary asymmetric induction of the starting alkene. 

Although simple isocyanates are not electrophilic enough to add to alkenes, electron-deficient isocyanates will add to alkenes. Chlorosulfonyl isocyanate is the most reactive and most commonly used isocyanate105-107. It undergoes stereospecific syn addition to alkenes. The carbonyl group adds to the most nucleophilic end of the double bond. The chlorosulfonyl group can be reductively hydrolyzed with sodium sulfite. Asymmetric induction will result from addition to... 

Subsequently, the difference in the attack angle on a double bond between a nucleophile and an electrophile was postulated by Houk et al. [33] to be a major factor responsible for the different sense of 1,2-asymmetric induction. Since transition state B is less hindered than A in the case of hydroboration of alkenes or borane reduction of ketones (Scheme 6.27, right), it was proposed that such reactions should have a stereochemistry opposite to that obtained in metal hydride reductions (Scheme 6.27, left). The experimental results, indeed, confirm the reversal of the product ratios [178]. 

In case the groups R or Z in VIII are chiral, the double bond plane gets diastereotopic and the approaches of Y from one and the other side of the bond become inequivalent (asymmetrical induction)—the choice of the approach will depend on the conformation of R. For the reactions of nucleophilic addition to alkenes and carbonyl compounds the sterical models represented by the Newman projection formulas XVII are usually invoked for the rationalization of stereoselectivities ... 

Asymmetric induction can be also accomplished through the use of a chirally modified nitro olefin. Sugar-based nitroalkenes participate in thermal [4 + 2] cycloaddition to form enantiomerically pure nitronates [55,97]. Alternatively, diastereoselective cycloadditions are possible with chiral nitroalkenes as illustrated on Scheme 16.15 [47]. The tandem double intramolecular cycloaddition of enantiopure nitro-alkene 62 containing a single stereogenic center provides nitroso acetal 63 with high diastereoselectivity (relative to the existing center) in moderate yield. The product is isolated as a mixture of isomers that is formed due to epimerization of the intermediate nitronate (not shown) and used toward total synthesis of daphnilactone B. 

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