Cyclic transition states reagent

A mechanism of the 1,2-addition of Grignard reagents to ketones has been suggested by Swain involving a six-membered cyclic transition state. Ashby proposed a detailed mechanism as shown in (l)-(2). 

Organometallic reagents and alkali metal amides can react via a cyclic transition state (Section II, B, 5) beginning with electrophilic attack at the most basic ring-nitrogen. As a result, sodamide (in dimethylaniline, 145°, 2 hr) yields the 4-amino derivatives (40% yield S)) methyl- or phenyl-magnesium iodides give the 4-adduct quantitatively.s ... 

Grignard reagents that contain a /3-hydrogen—e.g. 15—can reduce a carbonyl substrate by transfer of that hydrogen as a side-reaction. The so-called Grignard reduction is likely to proceed via a six-membered cyclic transition state 16 the alkyl group of alkylmagnesium compound 15 is thereby converted into an alkene 17. 

The aldehyde or ketone, when treated with aluminum triisopropoxide in isopropanol as solvent, reacts via a six-membered cyclic transition state 4. The aluminum center of the Lewis-acidic reagent coordinates to the carbonyl oxygen, enhancing the polar character of the carbonyl group, and thus facilitating the hydride transfer from the isopropyl group to the carbonyl carbon center. The intermediate mixed aluminum alkoxide 5 presumably reacts with the solvent isopropanol to yield the product alcohol 3 and regenerated aluminum triisopropoxide 2 the latter thus acts as a catalyst in the overall process ... 

Thus one of the transferred hydrogens conies from the aluminum reagent, and the other one from the solvent. In addition to the mechanism via a six-membered cyclic transition state, a radical mechanism is discussed for certain substrates. ... 

Allylboron compounds have proven to be an exceedingly useful class of allylmetal reagents for the stereoselective synthesis of homoallylic alcohols via reactions with carbonyl compounds, especially aldehydes1. The reactions of allylboron compounds and aldehydes proceed by way of cyclic transition states with predictable transmission of olefinic stereochemistry to anti (from L-alkene precursors) or syn (from Z-alkene precursors) relationships about the newly formed carbon-carbon bond. This stereochemical feature, classified as simple diastereoselection, is general for Type I allylorganometallicslb. 

It is noteworthy that reaction diastereoselectivity closely parallels the isomeric purity of the allyiboronates, thus underscoring the requirement that the method of reagent synthesis be highly stereoselective. The data presented in Table 1 also provide strong evidence for the involvement of chair-like, cyclic transition states, analogous to the transition states previously invoked for aldol reactions46. 

These reactions occur, presumably, via cyclic transition states with preferential placement of the allylic diisopropylcarbamate substituent in an equatorial position. The ( )-.vi -diastcreomer is available with much greater stereoselectivity by using the corresponding 1-diisopropyl-aminocarbonyl-2-propenyltitanium reagent (see Section D.1.3.3.3.8.)fi. 

Cyclic and open transition state models have been used to explain syn/anti stereoselectivity in these reactions1. The possible transition states (including boat B and chair C transition states) can be deduced from the E/Z geometry of the crotyl reagent and the imine. The postulated cyclic transition states for the preferred E geometry of the imine arc shown below. 

To explain this extremely high anti selectivity, a cyclic transition state has been proposed in which the a-substituent of the inline and the methyl group of the allenic reagent are aligned in a less sterically congested anti relationship15. 

Several types of compound undergo elimination on heating, with no other reagent present. Reactions of this type are often run in the gas phase. The mechanisms are obviously different from those already discussed, since all those require a base (which may be the solvent) in one of the steps, and there is no base or solvent present in pyrolytic elimination. Two mechanisms have been found to operate. One involves a cyclic transition state, which may be four, five, or six membered. Examples of each size are... 

The report suggests that the actual reagent may be a pentacoordinate allyl-siliconate, such as CH,CH=CHCH2Si F4Cs+, which reacts with an aldehyde via a six-membered cyclic transition state. 

The factors that control the stereochemical outcome of such rections can be illustrated by additions of enantiomeric allenylzinc reagents to (S)-lactic aldehyde derivatives [114]. The matched S/S pairing proceeds via the cyclic transition state A in which addition to the aldehyde carbonyl assumes the Felkin-Anh orientation with an anti arrangement of the allenyl methyl and aldehyde substituents (Scheme 9.29). The alternative arrangement B is disfavored both by the anti-Felkin-Anh arrangement and eclipsing of the allenylmethyl and aldehyde substituents. 

The degree of asymmetric induction with 119 increased in the order CF3 — Me < Et < Bu < Pr As with the alkoxyaluminum dichloride reagent (Sect. II1-A-2) the cyclic transition state model (Scheme 20) would predict a continuous... 

Various allylhalostannanes can transfer allyl groups to carbonyl compounds. In this case, the reagent acts both as a Lewis acid and as the source of the nucleophilic allyl group. Reactions with halostannanes are believed to proceed through cyclic transition states. 

Interestingly, silylated propargylic zinc reagents, such as 342, may be better viewed as the allenic zinc reagent 343 which reacts with an aldehyde via a cyclic transition state, affording only the a f/-homopropargylic alcohol 344 with 90% yield (Scheme 91) 22. Alkylzinc halides react only sluggishly with aldehydes or ketones. This reactivity can be... 

Zweifel and Hahn found that deprotonation of terminal allenes with -BuLi and subsequent addition of ZnCb leads to terminal allenylzinc reagents, which afford anti adducts upon addition to various aldehydes (Table 5)7. Branching in the aldehyde and allene substituents enhanced the anti syn ratio of adducts, in keeping with the previously proposed cyclic transition state for such additions. 

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