Diastereoselectivity transition state position

Indeed, early transition states favor the kinetic trans compound (reactive radical trap such as dimethyl fumarate). When later transition states are involved (octene case), the stability of the final products starts to influence the stereochemical outcome, and since the cis product is more stable than the trans, the diastereoselectivity of the process becomes lower. The same interpretation could also be used to rationalize the results depicted in equation 18.2 [41a]. Indeed, the allylation reaction is occurring via a relatively late transition state. Therefore, when R = H the stereoselectivity is low because the cis final product is more stable than the trans. When R = Me, the cis and trans products have almost the same stability, therefore the influenee of the transition state position on the stereochemical outcome vanishes and the diastereoselectivity is higher. 

With a-alkyl-substituted chiral carbonyl compounds bearing an alkoxy group in the -position, the diastereoselectivity of nucleophilic addition reactions is influenced not only by steric factors, which can be described by the models of Cram and Felkin (see Section 1.3.1.1.), but also by a possible coordination of the nucleophile counterion with the /J-oxygen atom. Thus, coordination of the metal cation with the carbonyl oxygen and the /J-alkoxy substituent leads to a chelated transition state 1 which implies attack of the nucleophile from the least hindered side, opposite to the pseudoequatorial substituent R1. Therefore, the anb-diastereomer 2 should be formed in excess. With respect to the stereogenic center in the a-position, the predominant formation of the anft-diastereomer means that anti-Cram selectivity has occurred. 

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. 

The diastereoselectivity of the reactions of (Z)-l-methyl-2-butenylboronate is greater than that of (Z)-l-chloro-2-butenylboronate, evidently because the smaller, more electronegative chlorine substituent has a greater preference to orient in the axial position of transition state 5 than the methyl group. Excellent diastereoselectivity has also been observed in reactions of 1-methyl-3,3-disubstituted 2-propenylboronates and aldehydes27,40. 

Carboxylates, which are chiral in the a-position totally lose their optical activity in mixed Kolbe electrolyses [93, 94]. This racemization supports either a free radical or its fast dynamic desorption-adsorption at the electrode. A clearer distinction can be made by looking at the diastereoselectivity of the coupling reaction. Adsorbed radicals should be stabilized and thus react via a more product like transition state... 

Finally, the most significant mechanistic feature of the Ramberg-Backlund rearrangement is the stereoselective formation of ds-olefin products, as a result of the preferential cis-positioning of the pair of R groups in the episulfone-forming transition state, variously attributed to London forces , to diastereoselectivity in carbanion formation and to steric attraction . However, with the use of stronger bases such as potassium t-butoxide °, the trans-olefin predominates (equation 52), apparently due to prior epimerization of the kinetically favoured cts-episulfone, and subsequent loss of the sulfur dioxide. Similarly, when the episulfone intermediates possess unusually acidic... 

The first total synthesis of (T)-arteannuin M was accessed using a tandem oxy-Cope/ene reaction.87 Divinylcyclohexanol 138 was heated in toluene and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to give compound 140 as a single diastereomer in 55-60% yield (Scheme 28). The diastereoselectivity is controlled by the pseudo-equatorial position of the alkyl group in the transition state 139. 

Substrate control This refers to the addition of an achiral enolate (or allyl metal reagent) to a chiral aldehyde (generally bearing a chiral center at the a-position). In this case, diastereoselectivity is determined by transition state preference according to Cram-Felkin-Ahn considerations.2... 

Wender et al. have demonstrated the power of the rhodium-catalyzed [5 + 2]-cycload-dition reaction discovered in their laboratories by synthesizing (+)-dictamnol (148) [33], Allenylvinylcyclopropane 145 was treated with rhodium biscarbonyl chloride dimer or rhodium tris(triphenylphosphine) chloride (Scheme 19.27). Both catalysts provided the cycloadduct 146 in 70-76% yield and high diastereoselectivity (8-9 1). The diaster-eoselectivity was attributed to the C8 hydroxyl group assuming a position on the less sterically encumbered exo face of the transition-state structure 147. 

High anti-diastereoselectivity (95 5 dr) and enantioselectivity of the major isomer (99% ee) were obtained when utilizing the combination of (R,R)-catalyst and (S)-aldehyde. This stereochemical outcome (Scheme 6.169) was explained in terms of the Cram rule proposed transition-state model. The substituent on the aldehyde would be located in an onti-relationship to the nitronate. As the largest subshtuent (RJ should be in an anti position to the carbonyl group of the carbonyl substrate, the combination of (R,R)-catalyst 186 and (S)-substrate (TS 1) was favored rather than that of (S,S)-catalyst 183 and (S)-substrate (TS 2) because of the steric repulsion between Rs (smallest substituent) and nitronate (Scheme 6.170). 

The phenyl or butyl substituent preferentially occupies a pseudo-equatorial position in the chair-like transition state which accounts for the observed diastereoselectivity. Since this extra stereogenic centre is quite far from the reacting centres diastereoselection is no longer complete. 

If additional catalysts are used, both acids and bases can have a positive influence on the reaction rate. Sometimes, the chemical yield and the diastereoselectivity of the formation of a-aminophosphonates are higher in two-component systems using preformed imines. In this case, due to the phosphonate <-> phosphite tautomerism, the addition to the imine could occur by either a four- or five-membered transition state ... 

The Mannich adducts are readily transformed to optically active a-amino-y-lac-tones via a one-pot diastereoselective reduction and lactonization sequence and the tosyl group exchanged for a Boc group via a two-step procedure. The cop-per(II) ion is crucial for the success of this reaction [21]. It has the properties necessary both to generate the enol species in situ and, in combination with the C2-symmetric ligand, coordinate it as well as the imine in a bidentate fashion. The reaction proceeds via a cyclohexane-like transition state with the R substituent of the enol in the less sterically crowded equatorial position, which is required to obtain the observed diastereoselectivity (Fig. 5). 

The origin of diastereoselectivity in the cascade process was rationalized through a comparison of four different transition states (Fig. 7.1).116 The major diastereomer was posited to originate from transition state TS-145, which minimizes the developing diaxial-1,3 interactions through placement of the isopropyl group in a pseu-doequatorial position. Because only (/i)-olefins were obtained, the origin of the minor diastereomer was attributed to the boat-like transition state TS-150. 

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