Carbonyl group, allylation reaction

In the elaboration of /Mactam derivatives, an allyl group has been introduced alpha to the carbonyl group by reaction of an a-bromo-/Mactam with an allyl trialkylstannane under radical conditions (equation 113)704. The allyl group is introduced in a stereospecific fashion, thus indicating how useful radical reactions can be in the synthesis of complex molecules ... 

Ort/io-metallated palladium complexes of azo and hydrazobenzene catalyze the reduction by H2 of nitroaromatics, alkenes, alkynes, and aromatic carbonyl compounds. A palladium-aryl or bond in the precursor complex is a requirement for catalytic activity. The ligands are themselves susceptible to reduction. The kinetics of the reaction under 1 atm H2 have been measured. Palladium(O) complexes catalyze the hydrostannolysis of allyl and allyloxy carbonyl groups. The reaction can be applied to the selective protection-deprotection of aminoacid derivatives see equation (9). Alkenyl cyclopropanes carrying electron-withdrawing substituents are selectively hydrogenolyzed by Pd(0)/PBu3 catalysts... 

Secondary alkyl halides Sjvj2 substitution occurs if a weakly basic nucleophile is used in a polar aprotic solvent, E2 elimination predominates if a strong base is used, and ElcB elimination takes place if the leaving group is two carbons away from a carbonyl group. Secondary allylic and benzyiic alkyl halides can also undergo S l and El reactions if a weakly basic nucleophile is used in a pro tic solvent. 

In ( )-[2-(l-propenyl)-l, 3-dithian-2-yl]lithium, no problem of EjZ selectivity arises. It is easily prepared by deprotonation of the allylic dithiane87,88 with butyllithium in THF, whereas deprotonation of the 2-propylidene-l, 3-dithiane requires the assistance of HMPA. The addition to saturated aldehydes proceeds with excellent y-regioseleetivity and anti selectivity88,89. As often observed in similar cases, aldehydes which bear an, p2-carbon atom adjacent to the carbonyl group give lower selectivities. The stereoselectivity decreases with ketones (2-bu-tanone y/a 84 16, antiisyn 77 23)88. The reaction with ethyl 2-oxopropanoate is merely nonstereoselective90, but addition of zinc chloride improved the syn/anti ratio to 96 4, leading to an efficient synthesis of ( )-crobarbatic acid. 

So far, only reactions in which the internal nucleophile is tethered to the nitrogen atom of the A -acyliminium ion have been discussed, however, cyclizations with nucleophiles attached to other positions are also possible. If the nucleophile is connected to the carbon atom adjacent to the carbonyl group, bridged azabicycloalkane derivatives are obtained in high yield by using the more reactive allyl- or propargylsilanes. 

It should be noted here that the lithium salt of hexamethyldisilazane li-HMDS 492 (and Na-HMDS-(486) and K-HMDS in Sections 5.1.2 and 5.1.3), which is readily obtained on treatment of a solution of HMDS 2 in hexane or THF with butyUithium at -78 °C, is not only a very useful and selective strong base, e.g. for Wittig reactions, but can also add to carbonyl groups to yield the silylated Schiff bases or nitriles (cf. Sections 4.7 and 5.1.3) or to nitriles to afford N-silylated ami-dines. Alkylation of the Li-HMDS 492, e.g. with allyl bromide, affords, furthermore, N,N-bis(trimethylsilylated) primary amines such as 43 [64]. The combina-... 

Allylic boranes such as 9-allyl-9-BBN react with aldehydes and ketones to give allylic carbinols. The reaction begins by Lewis acid-base coordination at the carbonyl oxygen, which both increases the electrophilicity of the carbonyl group and weakens the C-B bond to the allyl group. The dipolar adduct then reacts through a cyclic TS. Bond formation takes place at the 7-carbon of the allyl group and the double bond shifts.36 After the reaction is complete, the carbinol product is liberated from the borinate ester by displacement with ethanolamine. Yields for a series of aldehydes and ketones were usually above 90% for 9-allyl-9-BBN. 

Intramolecular reactions can also occur between carbonyl groups and allylic silanes. These reactions frequently show good stereoselectivity. For example, 7 cyclizes primarily to 8 with 4% of 9 as a by-product. The two other possible stereoisomers are not observed.98 The stereoselectivity is attributed to a preference for TS 7A over TS 7B. These are both synclinal structures but differ stereoelectronically. In 7A, the electron flow is approximately anti parallel, whereas in 7B it is skewed. It was suggested that this difference may be the origin of the stereoselectivity. 

Ene and Carbonyl-Ene Reactions. Certain double bonds undergo electrophilic addition reactions with alkenes in which an allylic hydrogen is transferred to the reactant. This process is called the ene reaction and the electrophile is known as an enophile A When a carbonyl group serves as the enophile, the reaction is called a carbonyl-ene reaction and leads to [3,-y-unsalurated alcohols. The reaction is also called the Prins reaction. 

Scheme 13.17 depicts a synthesis based on enantioselective reduction of bicyclo[2.2.2]octane-2,6-dione by Baker s yeast.21 This is an example of desym-metrization (see Part A, Topic 2.2). The unreduced carbonyl group was converted to an alkene by the Shapiro reaction. The alcohol was then reoxidized to a ketone. The enantiomerically pure intermediate was converted to the lactone by Baeyer-Villiger oxidation and an allylic rearrangement. The methyl group was introduced stereoselec-tively from the exo face of the bicyclic lactone by an enolate alkylation in Step C-l. 

Palladium(0)-catalyzed coupling reactions - i. e. the Heck and Sonogashira reactions, the carbonylative coupling reactions, the Suzuki and Stille cross-coupling reactions, and allylic substitutions (Fig. 11.1) - have enabled the formation of many kinds of carbon-carbon attachments that were previously very difficult to make. These reactions are usually robust and occur in the presence of a wide variety of functional groups. The reactions are, furthermore, autocatalytic (i.e. the substrate regenerates the required oxidation state of the palladium) and a vast number of different ligands can be used to fine-tune the reactivity and selectivity of the reactions. 

It is proposed that the reaction proceeds through (i) oxidative addition of a silylstannane to Ni(0) generating (silyl)(stannyl)nickel(n) complex 25, (ii) insertion of 1,3-diene into the nickel-tin bond of 25 giving 7r-allylnickel intermediate 26, (iii) inter- or intramolecular allylation of aldehydic carbonyl group forming alkoxy(silyl)nickel intermediate 27, and (iv) reductive elimination releasing the coupling product (Scheme 69). 

The prime functional group for constructing C-C bonds may be the carbonyl group, functioning as either an electrophile (Eq. 1) or via its enolate derivative as a nucleophile (Eqs. 2 and 3). The objective of this chapter is to survey the issue of asymmetric inductions involving the reaction between enolates derived from carbonyl compounds and alkyl halide electrophiles. The addition of a nucleophile toward a carbonyl group, especially in the catalytic manner, is presented as well. Asymmetric aldol reactions and the related allylation reactions (Eq. 3) are the topics of Chapter 3. Reduction of carbonyl groups is discussed in Chapter 4. 

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