1,4 addition product

The first HCN addition (eq. 3) occurs at practical rates above 70°C under sufficient pressure to keep butadiene condensed in solution and produces the 1,4- and 1,2-addition products (3-pentenenitrile [4635-87-4] 3PN, and 2-meth5i-3-butenenitrile [16529-56-9] 2M3BN) in a 2 to 1 ratio. Fortunately, thermodynamics favors 3PN (about 20 1) and 2M3BN may be isomerized to 3PN (eq. 4) in the presence of a nickel catalyst. 

Bromination of isoprene using Br2 at —5 ° C in chloroform yields only /n j -l,4-dibromo-2-methyl-2-butene (59). Dry hydrogen chloride reacts with one-third excess of isoprene at —15 ° C to form the 1,2-addition product, 2-chloro-2-methyl-3-butene (60). When an equimolar amount of HCl is used, the principal product is the 1,4-addition product, l-chloro-3-methyl-2-butene (61). The mechanism of addition is essentially all 1,2 with a subsequent isomerization step which is catalyzed by HCl and is responsible for the formation of the 1,4-product (60). The 3,4-product, 3-bromo-2-methyl-1-butene, is obtained by the reaction of isoprene with 50% HBr in the presence of cuprous bromide (59). Isoprene reacts with the reactive halogen of 3-chlorocyclopentene (62). 

The reaction of symmetncally substituted M.At -diaryloxamides with bromo-dimethylborane yielded 1,1- or 1,2-addition products according to the ratio of the reactants [114] (Table 30)... 

Both the 1,2-addition product and the 1,4-addition product aie derived from the same allylic caibocation. 

HCl addition to unsymmetrical dienes can be even more complicated. For example, HCl addition to isoprene (2-methyl-1,3-butadiene) might give four different 1,2-addition products and three different 1,4-addition products. 

Various competitive reactions can reduce the yield of the desired Michael-addition product. An important side-reaction is the 1,2-addition of the enolate to the C=0 double bond (see aldol reaction, Knoevenagel reaction), especially with a ,/3-unsaturated aldehydes, the 1,2-addition product may be formed preferentially, rather than the 1,4-addition product. Generally the 1,2-addition is a kinetically favored and reversible process. At higher temperatures, the thermodynamically favored 1,4-addition products are obtained. 

Active Figure 14.4 An electrostatic potential map of the carbo-cation produced by protonation of 1.3-butadiene shows that the positive charge is shared by carbons 1 and 3. Reaction of Br-wit n the more positive carbon (C3 blue) gives predominantly the 1.2-addition product. Sign in St wwW.thornSOneuU.com to see a simulation based on this figure and to take a short quiz. 

Of the 1,2-addition products, explain why 3,4-dibromo-3-methyl-hbutene (21%) predominates over 3,4-dibromo-2-methyl-l-butene (3%). 

With acetic acid as solvent 68 is still the major product (Scheme 32). The minor product (69) probably forms in preference to the 3,5-isomer because the quinoline free base is reacting the high yield of 68 can be rationalized in terms of a 1,4- or 1,2-addition product that is rapidly bromi-nated at C-3. The 6- and 8-positions substitute more slowly [62JCS283, 62JCS291 77HC(32-1)319]. Both the 6- and the 8-bromoquinolines were 3-brominated under neutral conditions (62JOC1318). 

Addition products are exclusively obtained from the addition of a-lithiatcd alkyl sulfones to a,/i-unsaturaled ketones5-6, in contrast, 1,4-adducts were obtained as a mixture of diastereomers from the reaction of these anions with a./l-unsaturated esters. The extent of the diastereoselection, however, was not reported6. 

Addition of 2-butenyl sulfone anions to 2-cyclopentenone and 2-cyclohexenone at low temperatures ( — 85 °C) gives mixtures of y-1, 4- and a-1,2-addition products. When these reactions are warmed to 1 2CC, then y-l,4-addition products predominate7,8. The lithium salts of the a-1,2-adducts rearrange to 1,4-adducts at 0°C. 

The stereochemical outcome of these reactions has been rationalized as arising from a "tram-de-calyl -like or trans-fused chair-chair -like transition state. The extension of these reactions to acyclic enones has not been successful and only y-1,2-addition products are formed153. 

In general the chiral additive (l/ ,2/J)-l,2-dimethoxy-l,2-diphenylethane was the most effective while (.S )-2.2 -diniethoxy-1,1 -binaphthalene and (1 / ,27 )-/V,/V,/V, A"-tetramethyl-1,2-diphcnyl-ethylenediamine induced only very low levels of enantiofacial differentiation. In the case of the acyclic enimines competing 1,2-addition products were also obtained7. 

When electrophilic addition is carried out on a compound with two double bonds in conjugation, a 1,2-addition product (15) is often obtained, but in most cases there is also a 1,4-addition product (16), often in larger yield ... 

If the diene is unsymmetrical, there may be two 1,2-addition products. The competition between two types of addition product comes about because the carbocation resulting from attack by Y is a resonance hybrid, with partial positive charges at the 2 and 4 positions ... 

In most cases, more 1,4- than 1,2-addition product is obtained. This may be a consequence of thermodynamic control of products, as against kinetic. In most cases, under the reaction conditions, 15 is converted to a mixture of 15 and 16, which is richer in 16. That is, either isomer gives the same mixture of both, which contains more 16. It was found that at low temperatures, butadiene and HCl gave only 20-25% 1,4 adduct, while at high temperatures, where attainment of equilibrium is more likely, the mixture contained 75% 1,4 product. 1,2 Addition predominated over 1,4 in the reaction between DCl and 1,3-pentadiene, where the intermediate was the symmetrical (except for the D label) HjCHC—CH—CHCH2D. Ion pairs were invoked to explain this result, since a free ion would be expected to be attacked by Cl equally well at both positions, except for the very small isotope effect. 

The enantioselective 1,4-addition addition of organometaUic reagents to a,p-unsaturated carbonyl compounds, the so-called Michael reaction, provides a powerful method for the synthesis of optically active compounds by carbon-carbon bond formation [129]. Therefore, symmetrical and unsymmetrical MiniPHOS phosphines were used for in situ preparation of copper-catalysts, and employed in an optimization study on Cu(I)-catalyzed Michael reactions of di-ethylzinc to a, -unsaturated ketones (Scheme 31) [29,30]. In most cases, complete conversion and good enantioselectivity were obtained and no 1,2-addition product was detected, showing complete regioselectivity. Of interest, the enantioselectivity observed using Cu(I) directly in place of Cu(II) allowed enhanced enantioselectivity, implying that the chiral environment of the Cu(I) complex produced by in situ reduction of Cu(II) may be less selective than the one with preformed Cu(I). 

The hydroboration of enynes yields either of 1,4-addition and 1,2-addition products, the ratio of which dramatically changes with the phosphine ligand as well as the molar ratio of the ligand to the palladium (Scheme 1-8) [46-51]. ( )-l,3-Dienyl-boronate (24) is selectively obtained in the presence of a chelating bisphosphine such as dppf and dppe. On the other hand, a combination of Pdjldba), with Ph2PC6p5 (1-2 equiv. per palladium) yields allenylboronate (23) as the major product. Thus, a double coordination of two C-C unsaturated bonds of enyne to a coordinate unsaturated catalyst affords 1,4-addition product On the other hand, a monocoordination of an acetylenic triple bond to a rhodium(I)/bisphosphine complex leads to 24. Thus, asymmetric hydroboration of l-buten-3-yne giving (R)-allenyl-boronate with 61% ee is carried out by using a chiral monophosphine (S)-(-)-MeO-MOP (MeO-MOP=2-diphenylphosphino-2 -methoxy-l,l -binaphthyl) [52]. 

More substituted 1,3-dienes or trienes containing a 1,3-diene unit react with amines to give 1,2-addition products in the presence of nickel (Eq. 4.50) or palladium (Eq. 4.51) catalysts [187,188]. 

Several examples of conjugate addition of carbanions carried out under aprotic conditions are given in Scheme 2.24. The reactions are typically quenched by addition of a proton source to neutralize the enolate. It is also possible to trap the adduct by silylation or, as we will see in Section 2.6.2, to carry out a tandem alkylation. Lithium enolates preformed by reaction with LDA in THF react with enones to give 1,4-diketones (Entries 1 and 2). Entries 3 and 4 involve addition of ester enolates to enones. The reaction in Entry 3 gives the 1,2-addition product at —78°C but isomerizes to the 1,4-product at 25° C. Esters of 1,5-dicarboxylic acids are obtained by addition of ester enolates to a,(3-unsaturated esters (Entry 5). Entries 6 to 8 show cases of... 

The relative reactivity of cyclopentadiene and ds-dichloroethylene toward triplet cyclopentadiene was found to be greater than 20 1 while that for cyclopentadiene and trans-dichloroethylene is less than 5 1. Thus the trans isomer is about four times more reactive toward the triplet cyclopentadiene than the cis isomer. An interesting temperature dependence of the product distribution of this reaction has been reported (Table 10.8). The data in Table 10.8 indicate that the relative amount of 1,4 addition [products (39) and (40)] is much more sensitive to temperature than 1,2 addition [products (35)—(38)], especially for the trans-olefin. The data also indicate that some rotation about the CHC1-CHC1 bond occurs in intermediate radicals derived from both cis- and trans-dichloroethylene. However, rotational equilibrium is not established at ring closure since the ratios of ds-dichlorocyclobutanes... 

In a series of experiments using various pressures of CO and H 0, with norbornadiene as the diene /44, 45/, we were able to verify an earlier suggestion /43/ that the 1,2 addition product norbornene is formed through a diene dissociation (Equation 43) and the 1,5 addition product nortricyclene through a CO dissociation (Equation 42). 

At lower temperature, the relative amounts of the products of the addition are determined by the relative rates at which the two additions occur 1,2-addition occurs faster so the 1,2-addition product is the major product. 

Figure 13.10 A schematic free-energy versus reaction coordinate diagram for the 1,2 and 1,4 addition of hbr to 1,3-butadiene. An allylic carbocation is common to both pathways. The energy barrier for attack of bromide on the allylic cation to form the 1,2-addition product is less than that to form the 1,4-addition product. The 1,2-addition product is kinetically favored. The 1,4-addition product is more stable, and so it is the thermodynamically favored product.

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