Regioselectivity addition reactions

Phenyltrimethyldisilene 15, produced by irradiation of the precursor 13 (X > 280 nm) in the presence of several alcohols, gives rise to the formation of 1 -alkoxy-2-hydrido-l,l,2-trimethyl-2-phenyldisilane (26) as the major product along with a small amount of the isomeric l-alkoxy-2-hydrido-l,2,2-trimethyl-l-phenyldisilane (27) (see Scheme 3). As shown in Table 3, very high regioselectivity was observed. This is the first example demonstrating a regioselective addition reaction to the unsymmetrically substituted disilenes. 

T. Nishikubo, et al., Soluble polymer-supported catalysts containing pendant quaternary onium salt residues for regioselective addition reaction of epoxy compound with active ester. Macromolecules 1994, 27(25), 7240-7247. 

Non-crosslinked polystyrene with salen ligand Non-crosslinked polystyrene with onium salt residues Non-crosslinked polystyrene copolymerised with a chiral phosphine ligand 14,765 0.5-3.8" 0.7-2.3 CH2Cl2,THF, EtOAc, DMF DMF,DMSO,DMA, toluene, anisole, MeOH,MeCN, diglyme Asymmetric epoxidation Regioselective addition reaction of phenyl glycidyl ether with S-phenyl thioacetate Pt-catalysed asymmetric hydroformylation of olefins Precipitation (methanol) (r) Precipitation (diethyl ether) (r) [68] [142] [143]... 

While testing two different catalysts, Tanaka found that cationic rhodium in a binary system (cationic Rh(I)/H8-binap) is effective in chemo- and regioselective addition reactions of terminal alkynes with acetylenedicarboxylate to form 1,2,3,4-tetra-substituted benzenes with excellent yield of 99% [9, 44, 45]. It is also important to note that this reaction is tolerant to a large number of functional groups, including alkenes, alkyl halides, and esters. Although cationic iridium complex Ir(I) did not give a positive result in the cycloaddition reactions, the authors showed that the catalytic system with neutral Ir(I) can facilitate cycloaromatization of dimethyl acetylenedicarboxylate and terminal alkynes [45]. 

Nune SK, Tanaka M (2007) Palladium-catalysed regioselective addition reaction of ethyl phenylphosphinate with terminal acetylenes ligand- and solvent-dependent regioselectivity. Chem Commun 2858-2860... 

Section 11 16 Addition reactions to alkenylbenzenes occur at the double bond of the alkenyl substituent and the regioselectivity of electrophilic addition is governed by carbocation formation at the benzylic carbon See Table 11 2... 

Conjugation of the newly formed double bond with the carbonyl group stabilizes the a p unsaturated aldehyde provides the driving force for the dehydration and controls Its regioselectivity Dehydration can be effected by heating the aldol with acid or base Normally if the a p unsaturated aldehyde is the desired product all that is done is to carry out the base catalyzed aldol addition reaction at elevated temperature Under these conditions once the aldol addition product is formed it rapidly loses water to form the a p unsaturated aldehyde... 

Anti-Markovnikov addition (Sections 6.8, 6.11) Addition reaction for which the regioselectivity is opposite to that predicted on the basis of Markovnikov s rule. 

A reiterative application of a two-carbon elongation reaction of a chiral carbonyl compound (Homer-Emmonds reaction), reduction (DIBAL) of the obtained trans unsaturated ester, asymmetric epoxidation (SAE or MCPBA) of the resulting allylic alcohol, and then C-2 regioselective addition of a cuprate (Me2CuLi) to the corresponding chiral epoxy alcohol has been utilized for the construction of the polypropionate-derived chain ]R-CH(Me)CH(OH)CH(Me)-R ], present as a partial structure in important natural products such as polyether, ansamycin, or macro-lide antibiotics [52]. A seminal application of this procedure is offered by Kishi s synthesis of the C19-C26 polyketide-type aliphatic segment of rifamycin S, starting from aldehyde 105 (Scheme 8.29) [53]. 

A synthetically useful diastereoselectivity (90% dc) was observed with the addition of methyl-magnesium bromide to a-epoxy aldehyde 25 in the presence of titanium(IV) chloride60. After treatment of the crude product with sodium hydride, the yy -epoxy alcohol 26 was obtained in 40% yield. The yyn-product corresponds to a chelation-controlled attack of 25 by the nucleophile. Isolation of compound 28, however, reveals that the addition reaction proceeds via a regioselective ring-opening of the epoxide, which affords the titanium-complexed chloro-hydrin 27. Chelation-controlled attack of 27 by the nucleophile leads to the -syn-diastereomer 28, which is converted to the epoxy alcohol 26 by treatment with sodium hydride. 

Only moderate induced diastereoselectivity is achieved in the addition reactions of lithium enolates of the following a-silyloxy ketones43 and carbohydrate-derived ketones44, deproto-nated in each case at the methylene group in a regioselective manner to benzaldehyde. 

An analogous regioselective effect of silver ions on an addition reaction of arene-diazonium ions was found by Ignasiak et al. (1975) with cyanide salts. Potassium cyanide yields diazocyanides (Ar— N2 — C = N see Sec. 6.6), i.e., C-coupling products, but with silver cyanide - albeit in low yield (7-9%) - diazoisocyanides (Ar—N2 — N = C) are formed (a better synthesis of diazoisocyanides is described in Sec. 6.4). 

Another interesting example is provided by the phenylethynylcarbene complex 173 and its reactions with five-, six-, and seven-membered cyclic enamines 174 to form bridgehead-substituted five-, six-, and seven-membered cycloalkane-annelated ethoxycyclopentadienes with high regioselectivity under mild reaction conditions (Scheme 38) [119,120]. In these transformations the phenylethynylcarbene complex 173 acts as a C3 building block in a formal [3+2] cycloaddition. Like in the Michael additions (reaction route F in Scheme 4), the cyclic electron-rich enamines 174 as nucleophiles attack the... 

Analogously, the 1,3-dipolar cycloaddition reaction of 2-diazopropane with propargyl alcohol 62b, performed at 0 °C in dichloromethane, was completed in less then 10 h and led to a monoadduct 63b with the same regioselective addition mode of 59 to the triple bond. The HMBC spectrum showed correlations between the ethylenic proton and the carbons C3 and C5 and between the methyl protons and the carbons C3 and C4. 

A variety of other addition reactions occurring regioselectively are also known. These include hydrocyanation, hydroalumination, hydrosilylation, and hydrozirconation. 

A few further general examples of zinc catalytic activity or reactivity include the following. Other zinc-containing systems include a zinc phenoxide/nickel(0) catalytic system that can be used to carry out the chemo- and regioselective cyclotrimerization of monoynes.934 Zinc homoenolates have been used as novel nucleophiles in acylation and addition reactions and shown to have general utility.935,936 Iron/zinc species have been used in the oxidation of hydrocarbons, and the selectivity and conditions examined.362 There are implications for the mechanism of metal-catalyzed iodosylbenzene reactions with olefins from the observation that zinc triflate and a dizinc complex catalyze these reactions.937... 

The regioselective addition of nitryl iodide to alkenes, followed by base-induced elimination, gives nitroalkenes. Nitryl iodide is generally prepared by the reaction of AgN02 and iodine. 

The regioselectivity in radical addition reactions to alkenes in general has successfully been interpreted by a combination of steric and electronic effects1815,47. In the absence of steric effects, regiochemical preferences can readily be explained with FMO theory. The most relevant polyene orbital for the addition of nucleophilic radicals to polyenes will be the LUMO for the addition of electrophilic orbitals it will be the HOMO. Table 10 lists the HOMO and LUMO coefficients (without the phase sign) for the first three members of the polyene family together with those for ethylene as calculated from Hiickel theory and with the AMI semiempirical method48. 

Most of the dienes investigated experimentally show high regioselectivity in radical addition reactions. The preferred position of attack is shown in Scheme 2. 

Trialkylstannanes undergo palladium-catalysed regioselective addition to 1,3-butadienes, as shown in reaction 12269. 

In the course of investigation into new C-C bond formation processes, Hiyama has developed an efficient nickel-catalyzed arylcyanation of alkynes.67 The addition reaction of an aryl-CN bond to alkyne affords aryl-substituted alkene nitrile in good yield. Good regioselectivity is reported in the case of unsymmetrical alkynes with two sterically different substituents. 

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