BF3-catalyzed

Most recent publications by Hartshorn and his collaborators introduce a note of caution with regard to the mechanistic interpretation of results obtained in BF3-catalyzed epoxide cleavage reactions. They point out the marked dependence of the course of the reaction on the solvent used, either... 

The mechanism of the carbo-Diels-Alder reaction has been a subject of controversy with respect to synchronicity or asynchronicity. With acrolein as the dieno-phile complexed to a Lewis acid, one would not expect a synchronous reaction. The C1-C6 and C4—C5 bond lengths in the NC-transition-state structure for the BF3-catalyzed reaction of acrolein with butadiene are calculated to be 2.96 A and 1.932 A, respectively [6]. The asynchronicity of the BF3-catalyzed carbo-Diels-Alder reaction is also apparent from the pyramidalization of the reacting centers C4 and C5 of NC (the short C-C bond) is pyramidalized by 11°, while Cl and C6 (the long C-C bond) are nearly planar. The lowest energy transition-state structure (NC) has the most pronounced asynchronicity, while the highest energy transition-state structure (XT) is more synchronous. 

An important contribution for the endo selectivity in the carho-Diels-Alder reaction is the second-order orbital interaction [1], However, no bonds are formed in the product for this interaction. For the BF3-catalyzed reaction of acrolein with butadiene the overlap population between Cl and C6 is only 0.018 in the NC-transi-tion state [6], which is substantially smaller than the interaction between C3 and O (0.031). It is also notable that the C3-0 bond distance, 2.588 A, is significant shorter than the C1-C6 bond length (2.96 A), of which the latter is the one formed experimentally. The NC-transition-state structure can also lead to formation of vinyldihydropyran, i.e. a hetero-Diels-Alder reaction has proceeded. The potential energy surface at the NC-transition-state structure is extremely flat and structure NCA (Fig. 8.6) lies on the surface-separating reactants from product [6]. 

In an investigation by Yamabe et al. [9] of the fine tuning of the [4-1-2] and [2-1-4] cycloaddition reaction of acrolein with butadiene catalyzed by BF3 and AICI3 using a larger basis set and more sophisticated calculations, the different reaction paths were also studied. The activation energy for the uncatalyzed reaction were calculated to be 17.52 and 16.80 kcal mol for the exo and endo transition states, respectively, and is close to the experimental values for s-trans-acrolein. For the BF3-catalyzed reaction the transition-state energies were calculated to be 10.87 and 6.09 kcal mol , for the exo- and endo-reaction paths, respectively [9]. The calculated transition-state structures for this reaction are very asynchronous and similar to those obtained by Houk et al. The endo-reaction path for the BF3-catalyzed reaction indicates that an inverse electron-demand C3-0 bond formation (2.635 A... 

Further studies by Garcia, Mayoral et al. [10b] also included DFT calculations for the BF3-catalyzed reaction of acrolein with butadiene and it was found that the B3LYP transition state also gave the [4+2] cycloadduct, as happens for the MP2 calculations. The calculated activation energy for lowest transition-state energy was between 7.3 and 11.2 kcal mol depending on the basis set used. These values compare well with the activation enthalpies experimentally determined for the reaction of butadiene with methyl acrylate catalyzed by AIGI3 [4 a, 10]. 

The influence of alkyl substituents on the asynchronous transition-state structure of the BF3-catalyzed carbo-Diels-Alder reaction of a,/ -unsaturated aldehydes with 1,1-dimethyl-l,3-butadiene derivatives has been investigated by Dai et al. [13]. 

In a combined experimental and theoretical investigation it was found that the / -alkyl group in the dienophile gave a steric interaction in the transition-state structure which supported the asynchronous transition-state structure for the Lewis acid-catalyzed carbo- and hetero-Diels-Alder reactions. The calculated transition-state energies were of similar magnitude as obtained in other studies of these BF3-catalyzed carbo-Diels-Alder reactions. 

The four different transition states in Fig. 8.10 were considered with BF3 as a model for the BLA catalyst in the theoretical calculations. It was found that the lowest transition-state energy for the BF3-catalyzed reactions was calculated to be 21.3 kcal mol for anti-exo transition state, while only 1.5 kcal mol higher in energy the syn-exo transition state, was found. The uncatalyzed reaction was calculation to proceed via an exo transition state having an energy of 37.0 kcal mol . The calculations indicated that the reaction proceeds predominantly by an exo transition-state structure and that it is enhanced by the coordination of the Lewis acid. 

Strong effects of the catalyst on the regioselectivity have been observed in the cycloadditions of a variety of heterocyclic dienophiles. Some results of the BF3-catalyzed reactions of quinoline-5,8-dione (21) and isoquinoline-5,8-dione (22) with isoprene (2) and (E)-piperylene (3) [25], and of the cycloadditions of 4-quinolones (23a, 23b) as well as 4-benzothiopyranone (23c) with 2-piperidino-butadienes, are reported [26] in Scheme 3.8 and Equation 3.2. The most marked... 

Entries 10 to 14 show reactions involving acetals. Interestingly, Entry 10 shows much-reduced stereoselectivity compared to the corresponding reaction of the aldehyde (The BF3-catalyzed reaction of the aldehyde is reported to be 24 1 in favor of the anti product ref. 80, p. 91). There are no stereochemical issues in Entries 11 or 12. Entry 13, involving two cyclic reactants, gave a 2 1 mixture of stereoisomers. Entry Mis a step in a synthesis directed toward the taxane group of diterpenes. Four stereoisomeric products were produced, including the Z E isomers at the new enone double bond. 

The choice of Lewis acid can determine if a chelated or open TS is involved. For example, all four possible stereoisomers of 1 were obtained by variation of the Lewis acid and the stereochemistry in the reactant.92 The BF3-catalyzed reactions occur through an open TS, whereas the TiCl4 reactions are chelation controlled. 

Dipole-dipole interactions may also be important in determining the stereoselectivity of Mukaiyama aldol reactions proceeding through an open TS. A BF3-catalyzed reaction was found to be 3,5-anti selective for several (3-substituted 5-phenylpentanals. This result can be rationalized by a TS that avoids an unfavorable alignment of the C=0 and C-X dipoles.97... 

Entry 10 is an example of the application of chelate-controlled stereoselectivity using TiCl4. Entry 11 also involves stereodirection by a (3-O-methoxybenzyloxy) substituent. In this case, the BF3-catalyzed reaction should proceed through an open TS and the (3-polar effect described on p. 96 prevails, resulting in the anti-3,5-isomer. 

In general, BF3 -catalyzed Mukaiyama reactions lack a cyclic organization because of the maximum coordination of four for boron. In these circumstances, the reactions show a preference for the Felkin type of approach and exhibit a preference for syn stereoselectivity that is independent of silyl enol ether structure.119... 

Reactions proceeding through open TS In this group, exemplified by BF3-catalyzed additions of allylic silanes and stannanes, the degree of stereochemical control is variable and often moderate. The stereoselectivity depends on steric factors in the open TS and can differ significantly for the E- and Z-isomers of the allylic reactant. 

The mechanism proceeds by BF3-catalyzed conversion of the Cr carbene complex to an enol , followed by attack on the BF3-complexed aldehyde. 

The formation of the syn adducts has been explained by considering that carboxylic acids or BF3 catalyze the formation of the ionic intermediate by stabilizing the methoxy ion. This intermediate can then collapse directly to the cis product. Reactions in methanol give instead mainly the trans-1,2-adduct, the solvent collapse from the back-side being very rapid. Furthermore, the difference in syn selectivity, slightly larger for 1,4- than for 1,2-addition, has been attributed to a smaller steric hindrance for syn methoxy (methanol) attack at C(4) than at C(2). 

Notes The bromo- variation, due to poor solubility is of limited use. Useful for the BF3-catalyzed methylenation of aldehydes in the presence of ketones. 

Other alkyl hypohalites usually add to carbon-carbon multiple bonds in a free-radical process.155-158 Ionic additions may be promoted by oxygen, BF3, or B(OMe)3.156-160 While the BF3-catalyzed reaction of alkyl hypochlorites and hypo-bromites gives mainly halofluorides,159 haloethers are formed in good yields but nonstereoselectively under other ionic conditions.156-158 160 In contrast, tert-BuOI reacts with alkenes in the presence of a catalytic amount of BF3 to produce 2-iodoethers.161 Since the addition is stereoselective, this suggests the participation of a symmetric iodonium ion intermediate without the involvement of carbocationic intermediates. 

In the manufacture of terephthalic acid by the oxidation of p-xylene, separation of the xylene from its isomeric mixture is necessary (see Section 2.5.2). An alternative process introduced in Japan uses the oxidation of p-tolualdehyde, which is obtained in good regioselectivity by the HF—BF3 catalyzed carbonylation of toluene without the necessity of separation of the isomers. 

An epoxide oxygen can serve as the leaving group in these rearrangements. For instance, Marshall and Kerschen (64) have found the BF3 catalyzed transformation 177+ 178. 

Polyols. Rychnovsky4 has used the BF3-catalyzed coupling of oxiranes with an alkyllithium of Ganem (12, 68) to obtain polyol chains. Thus the tetraalkyltin 1 reagent prepared from a P-hydroxy aldehyde reacts with the oxirane 2 in the presence of BF3 etherate (2.5 equiv.) to give the protected decanehexol 3. 

Each of the dihydropyranes thus obtained can be converted into their respective enelactones by BF3-catalyzed peroxidation 62), the hexenoside 52 then providing S-parasorbic acid 53 61). 

Acyltetrahydrofurans. These products can be obtained by BF3-catalyzed condensation of (Z)-4-hydroxy-l-alkenylcarbamates with aldehydes or ketones in high diastereo- and enantioselectivity.1 Use of a (Z)-anri-precursor (1) results in cis, trans, tram-tetrasubstituted tetrahydrofurans from aldehydes with high selectivity. 

The BF3-catalyzed reaction of a-aminoaldehydes with 10 is valuable for highly stereoselective synthesis of 2,3,5-trisubstituted pyrrolidines with all -cis configurations (Equation (50)).197 The stereochemical outcome like chelation-controlled stereochemistry might result from the inherent conformational arrangement of the aldehyde-BF3 complex. />-Quinoneimines, o-quinones, and a-alkoxyhydroperoxides undergo similar types of [3 + 2]-cycloadditions with allylsilanes to afford dihydro indoles, dihydrobenzofurans, and 1,2-dioxolanes, respectively.164,175,198... 

The most likely ending of this BF3-catalyzed polymerization is the loss of a proton from the carbocation at the end of the chain. This side reaction terminates one chain, but it also protonates another molecule of styrene, initiating a new chain. 

Anatabine (177) and A -methylanatabine are minor alkaloids of tobacco.1 5-167 Racemic 177 was synthesized by the BF3-catalyzed condensation (cf. Section II, A) of diethyl 3-pyridylmethylenebis-carbamate (176) with 1,3-butadiene and subsequent removal of the JV-ethoxycarbonyl group.168,169... 

Cyclocondensation with aldehydes (11, 332-333). The cyclocondensation of aldehydes with trimethylsilyloxydienes to provide 2,3-dihydro-4-pyrones has been studied in the most detail with this diene. Two pathways have been identified. In reactions catalyzed by ZnCl2, MgBr2, and a lanthanide shift reagent such as Eu(fod)3,2 a pericyclic pathway is suggested by isolation of the initial cycloadduct 2 with the expected endo-selectivity. In the presence of acid, this adduct is converted into a cis-2,3-dihydro-4-pyrone (3). Only traces of the trans-isomer (4) are formed. In contrast, the BF3-catalyzed reaction results... 

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