Primary alkyl iodides

As stated above, intermolecular coupling reactions between carbon atoms are of limited use. In the classical Wurtz reaction two identical primary alkyl iodide molecules are reduced by sodium. /i-Hectane for example, has been made by this method in 60%... 

Phenylsulfonyl)nitromethane is preferentially C-alkylated by benzylic halides and primary alkyl iodides, affording secondary a-nitrosulfones338. 

Nickel acetylacetonate, Ni(acac)2, in the presence of a styrene derivative promotes coupling of primary alkyl iodides with organozinc reagents. The added styrene serves to stabilize the active catalytic species, and of the derivatives examined, m-trifluoromethylstyrene was the best.274... 

A nickel-catalyzed conversion of primary alkyl iodides in neat diethylzinc, Scheme 29, was reported by Vettel et al33 Although many nickel(n) complexes are suitable catalysts for this reaction, the best results were obtained with... 

In 1996, the Knochel group reported their observations that primary alkyl iodides with a C=C bond and three or four carbons between the halogen and the sp2)C atom 300 reacted with dialkylzincs to form alkene 301 (Scheme 152).405 The reaction took place in the presence of a catalytic amount of Ni(acac)2. 

Primary and secondary alkylzinc iodides and benzylic zinc halides also undergo Ni-catalyzed reactions with various primary alkyl iodides and bromides.407-409 According to the procedure by Knochel and co-workers, the transformations with alkylzinc iodides, which are less reactive than the corresponding dialkylzincs, require the presence of two additives Bu4NI and 4-fluorostyrene (Scheme 155).407,408... 

Arylzinc bromides are also capable of reacting with functionalized primary alkyl iodides in the presence of Ni(acac)2-410 The couplings readily occurred in the presence of an equimolar amount of 4-trifluoromethylstyrene at -15 °C. 

Butenolides.1 When activated by silver trifluoroacetate, this furan is alkylated by primary alkyl iodides or ethyl a-iodoacetate to give 4-alkyl-2-butenolides (2) in 60-80% yield. 

Ohtomi et al. (1976) have studied the catalytic effect of polypode ligands, such as [ 116] on the reactions of alkyl halides under liquid-liquid phase-transfer conditions (Table 34). Primary alkyl iodides are seen to be more reactive than the corresponding bromides. In contrast, the reactivity towards CN- declines in the order RBr > RI > RC1. It is interesting to note that this order differs from that observed in solid-liquid two-phase systems catalysed by crown ethers (Cook et al., 1974). 

At a platinum anode in acetonitrile, a primary alkyl iodide undergoes oxidation to give a carbocation that reacts with the solvent to give an intermediate (1), and the latter species is converted to an A-alkylacetamide (2) during an ether-water workup [5] ... 

Functionalized organozinc halides are best prepared by direct insertion of zinc dust into alkyl iodides. The insertion reaction is usually performed by addition of a concentrated solution (approx. 3 M) of the alkyl iodide in THF to a suspension of zinc dust activated with a few mol% of 1,2-dibromoethane and MeaSiCl [7]. Primary alkyl iodides react at 40 °C under these conditions, whereas secondary alkyl iodides undergo the zinc insertion process even at room temperature, while allylic bromides and benzylic bromides react under still milder conditions (0 °C to 10 °C). The amount of Wurtz homocoupling products is usually limited, but increases with increased electron density in benzylic or allylic moieties [45]. A range of poly-functional organozinc compounds, such as 69-72, can be prepared under these conditions (Scheme 2.23) [41]. 

Primary alkyl iodides and bromides are excellent substrates for the Victor Meyer reaction, providing a route to both substituted and unsubstituted nitroalkanes (Table i. i).63,65,70,7i formation of the corresponding nitrite ester is a side-reaction and so the nitroalkane is usually isolated by distillation when possible. The reaction of primary alkyl chlorides with silver nitrite is too slow to be synthetically useful. Secondary alkyl halides and substrates with branching on... 

Under these conditions, a broad range of polyfunctional alkyl iodides are converted to the corresponding organozinc halides in high yields . In the case of primary alkyl iodides, the insertion occurs at 40-50 °C whereas secondary alkyl iodides already react at 25-30°C. Secondary alkyl bromides also react under these conditions , but primary alkyl bromides are usually inert with this type of activation and much better results are obtained by using Rieke zinc L Thus, the reduction of zinc chloride with finely cut lithium and naphthalene produces within 1.5 h highly reactive zinc (Rieke zinc). 

This has led to the discovery of electron-deficient styrenes, such as those shown in Figure 2. As detailed later, these ligands have been shown to be effective for the Ni-catalyzed alkylation of organozincs with primary alkyl iodides and bromides91. More recently, Fu88k has reported that a catalyst consisting of Ni(COD)2 and s-Bu-Pybox (3) is satisfactory even for the reaction of primary alkylzincs with secondary alkyl bromides... 

Following a report in 1992 on the reaction of /3-hydrogen-containing alkyl iodides with alkyl-, aryl- and alkenyl-9-BBN derivatives in the presence of Pd(PPh3)4 and K3PO4208, Knochel and coworkers made an interesting and potentially important observation on the effect of proximal -bonds shown in Scheme 2790. This may have paved the way to their subsequent discovery of the Ni-catalyzed reaction of alkylzincs with primary alkyl iodides in the presence of an electron-deficient styrene or acetophenone90,91 (Scheme 74)... 

SCHEME 74. Ni-catalyzed reaction of organozincs with primary alkyl iodides promoted by electron-deficient styrenes or acetophenone... 

Ketone synthesis. Di alkylation of bis(phenylthio)methane is possible if the anion is prepared with n-Bul.i TMF.DA in hexane at 0C. Highest yields arc obtained with primary alkyl iodides.1... 

As stated above, intermolecular coupling reactions between carbon atoms are of limited use. In the classical Wurtz reaction two identical primary alkyl iodide molecules are reduced by sodium. n-Hectane (C100H202), for example, has been made by this method in 60% yield (G. Stallberg, 1956). The unsymmetrical coupling of two alkyl halides can be achieved via dialkylcuprates. The first halide, which may have a branched carbon chain, is lithiated and allowed to react with copper(I) salts. The resulting dialkylcuprate can then be coupled with alkyl or aryl iodides or bromides. Although the reaction probably involves radicals it is quite stereoselective and leads to inversion of chiral halides. For example, lithium diphenyl-cuprate reacts with (R)-2-bromobutane with 90% stereoselectivity to form (S)-2-phenylbutane (G.M. Whitesides, 1969). 

The evidence for single-electron transfer (SET) in the reactions of lithium aluminium hydride (LAH) with hindered primary alkyl iodides is overwhelming. A study has now shown for the first tune that SET may also be involved in reactions of LAH with unhindered, unsubstituted primary alkyl iodides, the particular substrate studied being 1-iodoctane.98 A theory of the rates of, k 2 reactions and then relation to those of outer-sphere bond-rapture electron transfers has been presented in detail.99 A unified approach is introduced in which there can be a flux density for crossing the transition state, which is either bimodal, one part leading to, k 2 and the other to ET products, or... 

Alkylation. Reaction of this reagent (1) with primary alkyl iodides or bromides results in derivatives which are cleaved by either HBr/HOAc or HgCl2 to ketones (equation I), The products can also be desulfurized to substituted cyclopropanes. 

Alkylation of cyclopropanecarboxylic acid esters,6 Deprotonation of methyl silyloxycyclopropanecarboxylates (1), prepared as shown, is possible with LDA in THF at — 78°. The resulting anions react with primary alkyl iodides and benzylic or allylic bromides to give 2 in high yield. These products are cleaved by F to methyl 4-ketocarboxylates 3. 

Reduction of alkyl halides and sulfonate estersThis reagent in HMPT is Nomcwhat more effective than NaBH3CN for reduction of primary alkyl iodides and allylic and benzylic iodides. It is also preferred for reduction in benzene or CH2C12. 

Alternatively, a more nucleophilic anionic reagent can be generated by selective cleavage of a single trimethylsilyl group with methyl lithium-lithium bromide complex. This 1ithiobutadlyne derivative will react with electrophiles such as carbonyl compounds or primary alkyl iodides. 2... 

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