Kinetic control addition

With pteridine (1) the covalent hydration is a complex matter since the general acid-base catalyzed reaction provides a good example of a kinetically controlled addition to the... 

Hexamethylditin readily adds to allene in the presence of Pd(PPh3)4 to give an allyltin compound. An unsymmetrically substituted allene such as 1,1-dimethylal-lene undergoes kinetically controlled addition at lower temperatures, whereas at higher temperatures thermodynamically more stable products are formed (Scheme 16.61) [66],... 

Dimethylpyrimido[4,5-f]pyridazine-5,7-dione 23 and its derivatives undergo attack at both C-3 and C-4. Under conditions of kinetic control, addition occurs preferentially at the more electron-deficient C, whereas thermodynamic control conditions, or the use of bulkier nucleophiles, favor addition at the less hindered position 3. This duality is illustrated by the addition of Grignard and organolithium reagents to C of 3-chloro analogue 24 (Equation 9), whereas stabilized nucleophiles such as the anion of nitromethane add at C-3 (Scheme 10) <2000CHE975>. Displacement of the 3-chloride occurs also upon treatment of 24 with amines (Equation 10) <2000CHE1213>. 

In addition of organometallic reagents to some arynes, prior counterion complexation with the substituent can direct the incoming group to the ortho position (kinetic control). Addition of alkyllithiums to oxazolinyl (OXZ) aryne (51) to give the ortho product (52) is explained in this manner. In contrast, lithium dialkylcuprates add to the aryne (51) exclusively at the meta position. This is ascribed to thermodynamic control of the reaction, which results in the formation of the more ligated and stable adduct (S3).i2 Control of nucleophilic addition to arynes by complex-induced proximity effects has not been explored with substituents other than OXZ,83 but has considerable synthetic potential if it can be achieved, say through solvent manipulation. 

Stereoelectronic effects should also play an important role in the nucleophilic 1,4-additions of anions to conjugated systems. These effects should therefore influence the Michael reaction as well as the hydrocyanation of a,6-unsaturated ketones. Studies on these reactions provided evidence that the kinetically controlled addition of a nucleophile to a cyclohexenone derivative is indeed subject to stereoelectronic effects. 

Under more equilibrating conditions such as alkoxide bases in alcohol solution or amide bases in liquid ammonia, enolisation occurs to give the extended enolate 83 which is then alkylated in the a-position by alkyl halides. At first this seems the most difficult combination to achieve thermodynamic enolisation followed by kinetically controlled addition of an electrophile, but it is in fact a common result achieved with a variety of bases. Examples include the synthesis of pentethylcyclanone 100, an anti-tussive drug, by alkylation of the enone 103, the aldol dimer of cyclopentanone. Disconnection at the branchpoint to the available alkyl halide 102 X = Cl requires a-alkylation of the extended enolate 101 derived from the cyclopentanone aldol dimer27 103. This is easily achieved by sodium amide in toluene.28... 

In 1973 Tsuchihashi reported asymmetric induction during carbon-carbon bond formation between nucleophilic malonate and electrophilic enantiomerically pure styryl sulfoxide 2, producing intermediate diastereomeric carbanions 3a and 3fe (eq 2) (J) Selective formation of diastereomer 2 this irreversible, kinetically controlled addition was rationalized in terms of the preference for an a-sulfinyl carbanion to have the carbon lone-pair orbital trans to the sulfinyl oxygen orbital in a polar solvent. 

G(d) with ZPEC computed the exo reactivity (0.0581) to be smaller than endo reactivity (0.0657) and subsequently, endo selectivity for the kinetically controlled addition of cyclopropene to butadiene was 0.0076. It was responsible for the... 

Solvent and temperature may also affect the product ratio. Thus in the kinetically controlled addition of cyclopentadiene to E-methyl 2-butenoate, the proportion of endo product increases with the polarity of the solvent, and the product ratio was also slightly affected by the temperature of the reaction. A mixture of the endo and exo products was obtained, with the exo isomer predominant in some solvents (e.g. MesN at 30 °C) and the endo in others (e.g. EtOH, AcOH). 

NCS in pyridine gave 2,6-diphenyldihydro-4H-thiopyran-4-one. Full details of the kinetically controlled additions of various photogenerated carbenes and nitrenes to 4-t-butylthian have been published. Only -aryl sulphimides with equatorial S—N bonds were obtained from conformationally mobile or rigid thians and from CIS- and rra s-l-thiadecalins. ... 

Another difference between dimethylsulfonium methylide and dimethyloxo-sulfonium methylide has to do with the stereoselectivity of epoxide formation. Dimethylsulfonium methylide tends to add to ketones from the less-hindered side while dimethyloxosulfonium methylide tends to give the more stable epoxide (entries 7 and 8). It may be presumed that the stereoselectivity of epoxide formation is influenced by the reversibility of the addition step with dimethylsulfonium methylide giving the product of kinetically controlled addition and dimethyloxosulfonium ylide the product of thermodynamically controlled addition. ... 

Kinetically controlled addition of hydrogen halide to acylaminoacrylic ester leads to a-halo-a-acylamino-propionic acid ester (76), which gradually rearranges in the reaction solution into the p-halo-derivative 236, 241, 301). The a-halo compound can be captured with mercaptans, alcohols or water, forming the appropriate a-substituted a-acylamino-propionic acid esters (77) 197,199). 

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