Transition structures chair-like

This conclusion has been applied in the Ireland-Claisen rearrangement 5.56 —> 5.58, which is one of the most frequently used [3,3] sigmatropic rearrangements, because it sets up two usefully substituted stereogenic centres with high levels of predictability, stemming from the chair-like transition structure 5.57. 

The mechanism A very detailed mechanistic study of this phosphoramide-catalyzed asymmetric aldol reaction was conducted by the Denmark group (see also Section 6.2.1.2) [59, 60], Mechanistically, the chiral phosphoramide base seems to coordinate temporarily with the silicon atom of the trichlorosilyl enolates, in contrast with previously used chiral Lewis acids, e.g. oxazaborolidines, which interact with the aldehyde. It has been suggested that the hexacoordinate silicate species of type I is involved in stereoselection (Scheme 6.15). Thus, this cationic, diphosphoramide silyl enolate complex reacts through a chair-like transition structure. 

The basic principles of the mechanism of this Lewis-base-catalyzed aldol reaction have already been described in Section 6.2.1.1. With regard to the course of the enantio- and diastereoselective formation of aldol adducts with two stereogenic centers, it is proposed that synthesis of anti-products proceeds via a chair-like transition structure. A distinctive feature of the cationic transition state complex is a hexacoordinated silicon atom bearing two chiral phosphoramide molecules as ligands (Scheme 6.30). 

The high trans diastereoselectivity often observed in cyclisations involving substrates bearing substituents at the C4 position, such as 74, can be rationalised by comparing the two possible chair-like transition structures (Scheme 5.49). Positioning the R group substituent in a pseudo-equatorial orientation relieves the A1,3 strain observed for the alternative conformer with the same substituent in a pseudo-axial position.81... 

With the stereogenic center in the -position the induced diastereoselectivity is controlled by the preferential equatorial orientation of the substituent in a chair-like transition structure. However, the selectivity is higher (96.3 3.7) than could be anticipated from a simple comparison with the ratio of the equatorial-ly and axially orientated methyl group in methylcyclohexane (95 5). 

There are a number of Se2 reactions which are not open-chain reactions. The electrophile is typically an aldehyde coordinated at the time of reaction to an electropositive atom like boron, tin or zinc on the stereogenic centre. These reactions usually use cyclic, chair-like transition structures, are called metallo-ene reactions, and are inherently syn overall. 

Figure 10-1. Cyclic chair-like transition structure.

The reaction of highly strained allylsilacyclobutanes with aldehydes has recently been developed to produce homoallylic alcohols with a high degree of re-gio- and stereoselectivity (Scheme 10-36) [63]. These species are structurally akin to the allyltrialkylsilanes, but are more mechanistically aligned with the allyltri-halosilanes. The -2-butenylsilacyclobutane upon reaction with an aldehyde at elevated temperature will produce almost exclusively the anti homoallylic alcohol. When the Z-2-butenylsilacyclobutane is used instead, the syn homoallylic alcohol is obtained. The mechanism proposed for the reaction involves the association of aldehyde and allylsilacyclobutane to form an activated pentacoordinate silicon complex. A closed, chair-like transition structure is proposed to account for the observed stereoselectivity in the reaction (Scheme 10-36k A theoretical examina-... 

The stereochemical course of the thermally promoted addition of allylic trialkyl-stannanes to aldehydes is dependent upon the geometry of the 2-butenyl unit [67, 69], The reaction is believed to proceed via a cyclic, six-membered, chair-like transition structure. Reaction of an -2-butenylstannane provides the anti homoallylic alcohol, while an Z-2-butenylstannane affords the corresponding syn homoallylic alcohol (Scheme 10-37). The allylation of aldehydes with allylic stannanes has also been performed under high pressure and neutral conditions [70]. The stereochemical outcome of the reaction of E- and Z-2-butenylstannanes with aldehydes under high pressure was almost identical to the results obtained thermally. 

The InCl3-promoted reaction of enantiomerically enriched a-alkoxystannanes 305 with achiral aldehydes produces a mixture of homoallylic alcohols with a high degree of relative diastereoselectivity and excellent enantioselectivity (Scheme 10-106). A plausible explanation first invokes the formation of indium reagent 306 produced via anti Se2 attack of lnCl3 on the a-alkoxystannane. Addition to the aldehyde can then occur via the chair-like transition structure xxxvii to afford the anti homoallylic alcohol preferentially. 

The failure to insert quaternary vinyl groups in a cyclization process is limited to 1,6-diene systems [17]. When a similar competition for selective insertion is attempted on a 1,5-diene, cyclization occurs because of the inherent entropic advantage of five-membered ring formation (Eq. 59). The close approach of the bulky organometallic to the axial alkoxy substituent in the chair-like transition structure (Fig. 12b) causes the reaction to proceed through the less hindered boat formation (Fig. 12a). 

In addition to their ability to assemble bicyclic structures on a monocyclic scaffold, the organoyttrium catalysts can also convert trienes to bicyclics in a sequential process (Eqs. 60, 61) [17]. Both five- and six-membered rings can be constructed at will. In these cases the stereochemistry at the bridgeheads is a result of the chair-like transition structures operative during the intramolecular olefin insertions (Schemes 1,2). There are two notable features of this reaction. The first is that after the initial olefin insertion a 5-exo cyclization at the allyli-... 

Conformational control through electrostatic stabilization is also observed with an alkoxy substituent at the C3 carbon of a six-membered ring oxocarbenium ion intermediate. In contrast to the trans product obtained with an alkyl substituent, nucleophilic addition to 14 (X = OBn, Fig. 4.6) in the presence of a Lewis acid afforded the contrasteric 1,3-cis product cis-15 (Fig. 4.6). The cis product arises from addition of the nucleophile to the pseudoaxial conformer 16, which would be favored for X = OBn [8]. The high selectivity for the contrasteric cis product indicates that the electrostatic stabilization compensates for the development of steric interactions between C3 alkoxy substituents and the approaching nucleophile in the chair-like transition structure [27]. Without the electrostatic stabilization, substituents at the C3 carbon reside in pseudoequatorial orientation of the oxocarbenium ion 77 to give the sterically preferred 1,4-trans product trans-15. 

The ring closure of cyclic 2-but-3-enylcycloalkyl radicals (Fig. 7.3) is similar to that of the open-chain system, except that the constraints of the ring impose an almost exclusive 1,2-cis stereochemistry [3, 4]. The critical 1,5-selectivity is still largely cis, and it is this selectivity that has found the most use in the synthesis of polycyclic natural products [5, 6]. In the context of the 2-but-3-enylcyclopentyl radical cyclization, it was argued [7] that the l,5-c stereochemistry is favored because the chair-like transition structure 8a (Fig. 7.4) can achieve effective overlap between the SOMO and the radical center and the olefin n orbitals, with less strain than the other possible chair Sb. 

The investigators foimd that both the thermal and enzyme-catalyzed reactions of (E)-[9- H jchorismate led to rapid release of tritiated water, whereas the reactions of the (Z) isomer did not. From this they concluded that both the enzyme-catalyzed and thermal reactions involve a chair-like transition structure. 

For an explanation of the stereoselectivity, the chair-like transition structures (52A and 52B) in which the mercury is chelated by the enolate o tygen and the aldehydic o tygen have been proposed by Machado et al. and Perrier and Middleton fScheme 12.141. This transition model would account for the observed stereoselectivity concerning the newly formed hydroxy group at C-5. In the transformation of 14 15a, while the transition structure 52A giving 15a has no severe steric repulsion, that of 52B giving the 5-epimer of 15a suffers 1,3-diaxial interactions. In the reaction of 53 45b, the favored transition structure would be 54B, giving 3,5-trans-isomer 45b as the major product... 

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