Nucleophilic addition products

The Pd—C cr-bond can be prepared from simple, unoxidized alkenes and aromatic compounds by the reaction of Pd(II) compounds. The following are typical examples. The first step of the reaction of a simple alkene with Pd(ll) and a nucleophile X or Y to form 19 is called palladation. Depending on the nucleophile, it is called oxypalladation, aminopalladation, carbopalladation, etc. The subsequent elimination of b-hydrogen produces the nucleophilic substitution product 20. The displacement of Pd with another nucleophile (X) affords the nucleophilic addition product 21 (see Chapter 3, Section 2). As an example, the oxypalladation of 4-pentenol with PdXi to afford furan 22 or 23 is shown. 

There is also evidence for stable 3,4-adducts from the X-ray analysis of 2-amino-4-ethoxy-3,4-dihydropteridinium bromide, the nucleophilic addition product of 2-aminopteridine hydrobromide and ethanol (69JCS(B)489). The pH values obtained by potentiometric titration of (16) with acid and back-titration with alkali produces a hysteresis loop, indicating an equilibrium between various molecular species such as the anhydrous neutral form and the predominantly hydrated cation. Table 1 illustrates more aspects of this anomaly. 2-Aminop-teridine, paradoxically, is a stronger base than any of its methyl derivatives each dimethyl derivative is a weaker base than either of its parent monomethyl derivatives. Thus the base strengths decrease in the order in which they are expected to increase, with only the 2-amino-4,6,7-trimethylpteridine out of order, being more basic than the 4,7-dimethyl derivative. 

We have recently developed a novel method for the generation of alkylideneallyl cations from alkylidenecyclopropanone acetals (8, 9). This method provides a nice opportunity to examine the selectivity of reactions of the ambident cation with various nucleophiles including siloxyalkenes (10) and furans (11). The reaction of the cation with the carbon nucleophiles gives [4 + 3] and [3 + 2] cycloaddition products as well as simple nucleophilic addition products. These results are summarized in this chapter. 

Bolm and co-workers expanded the diastereoselective lithiation to include the ri -cyclopentadienylrhenium(l) tricarbonyl oxazoline complex 451 (Scheme 8.148). The selectivity was determined to be 9 1 favoring diastereomer 452. The strucmre of 452 was determined by crystallography. Interestingly, lithiation of 451 with jec-butyllithium resulted in the formation of nucleophilic addition products. 

The reaction of the racemic lactol, 5-(ten-butyldiphenylsilyloxymethyl)tetrahydro-2-furanol, with methyltitanium triisopropoxide yielded two racemic nucleophilic addition products in a 12 1 ratio syn vs. anti configuration had to be determined104 (see p 469). 

A farther example of the same type of rearrangement is provided by the observation of Komfeld and oo-workers,888 drawn durim lla-ir synthesis of lysergic acid, that treatment of the 0,y-epoxy ester derivative shown in Eq. (509) with the base saroosine (tbe ethyl ester of A -methylglydue) led to a lactone instead of the desired nucleophilic addition product. 

An indirect PET methodology known as redox photosensitization has been developed by Pac [45] and Tazuke [64] for achieving higher yields of nucleophile addition product to alkene cation radicals. One recent example of this approach may be mentioned by illustrating anti-Markonikov alcohol addition (e.g. 61-62) to non conjugated olefin 61 using biphenyl as cosensitizer [65]. More examples on this topic can be found in Farid [5] and Mariano s [11] reviews. 

In this synthesis (Scheme 6), the C2-symmetri-cal triacetonide of D-mannitol (32) is converted via the epoxide 33 and its nucleophilic addition product 34 to the propargylic alcohol derivative 35. From this intermediate, the Z-configured vinyl iodide 36 is stereoselectively obtained by hydroalumination/iodination. The Pd-catalyzed Heck cyclization then affords the isomerically pure product 37, which represents a potential building block for the synthesis of la,2y5,25-trihy-droxy-vitamin D, following the classical Wittig strategy of Lythgoe. 

What nucleophiles add to carbonyl groups This cannot be predicted solely on the trends in nucleophUicity learned in Chapter 7. Only some of the nucleophiles that react well in nucleophilic substitution at sp hybridized carbons give reasonable yields of nucleophilic addition products. 

Purines react with acylating agents such as chloroformates or diethyl pyrocarbonate to give non-isolable A -acyl salts, which can suffer various fates following nucleophilic addition products of cleavage of either ring have been observed, as have recyclisation products. 

Thermal reversion of 677-1,3,5-oxaselenazines 170 generates 1,3-selenaza-l,3-butadienes 171 which prove to be useful reactive intermediates in synthesis <1997CL701> (cf Section 9.15.6.2.2, Table 6, and Schemes 37-39). Thus, treatment of oxaselenazines 170 with excess alcohol or thiol at reflux affords the corresponding ring-opened products of nucleophilic addition (Table 7). No nucleophilic addition product was observed in the attempted reaction of 170 with propylamine <2001BCJ511>. 

Formation of vinyl acetate by the reaction of ethylene with Pd(OAc)2 can be understood by the acetoxypalladation and )3-H elimination (path a). No hydride shift occurs because the acetoxy group is electron-attracting. In addition, ethylene glycol monoacetate (9) is formed as a nucleophilic addition product in the presence of nitrate anion (path b) [13]. Formation of glycol monoacetate is explained by the displacement of Pd-OAc with a nitrate anion, followed by hydrolysis of the nitrate ester. 

An acetylide ion is another example of a carbon nucleophile that reacts with an aldehyde or a ketone to form a nucleophilic addition product. When the reaction is over, a weak acid (one that will not react with the triple bond, such as the pyridinium ion shown here) is added to the reaction mixture to protonate the alkoxide ion. 

In Section 17.18, we saw that nucleophiles react with a, S-unsaturated aldehydes and ketones, forming either direct (nucleophilic) addition products or conjugate addition products. 

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