Homoallylic chlorides

The cyclopropylmethyl cation has recently been generated in the gas phase from both homoallyl chloride and cyclopropylmethyl chloride and studied using collisional activated dissociation mass spectrometry.216 Interestingly, cyclobutyl chloride, which yields the cyclopropylmethyl cation in the condensed phase, gives a substantial amount of the bicyclobutonium ion in the gas phase. 

With the ruthenium(I) catalyst [(OC)4Ru2(OAc)2]n (see Section 1.2.1.2.4.2.6.3.1.), cis selectivity was observed in cyclopropanation of trisubstituted alkenes (e.g. 2-methylbut-2-ene, 2,5-dimethylhexa-2,4-diene) with methyl diazoacetate. Furthermore, the interplay between steric, electronic, and lipophilic interactions can occasionally result in enhanced cis selectivity for an individual reaction. Notably, certain homoallyl chlorides were consistently cyclo-propanated by diazoacetates with pronounced cis selectivity in the product cyclopropanes 4 with various catalysts. 

C4H7+ ions were generated by collisionally activated dissociation (CAD) in the gas phase from various precursors. Mass spectrometric analysis showed that homoallyl chloride and cyclopropylmethyl chloride generated primarily cation 103, whereas cyclobutyl chloride gave a substantial amount of bicy-clobutonium ion 104. 

The acylpalladium complex formed from acyl halides undergoes intramolecular alkene insertion. 2,5-Hexadienoyl chloride (894) is converted into phenol in its attempted Rosenmund reduction[759]. The reaction is explained by the oxidative addition, intramolecular alkene insertion to generate 895, and / -elimination. Chloroformate will be a useful compound for the preparation of a, /3-unsaturated esters if its oxidative addition and alkene insertion are possible. An intramolecular version is known, namely homoallylic chloroformates are converted into a-methylene-7-butyrolactones in moderate yields[760]. As another example, the homoallylic chloroformamide 896 is converted into the q-methylene- -butyrolactams 897 and 898[761]. An intermolecular version of alkene insertion into acyl chlorides is known only with bridgehead acid chlorides. Adamantanecarbonyl chloride (899) reacts with acrylonitrile to give the unsaturated ketone 900[762],... 

Organoboranes are reactive compounds for cross-coupling[277]. The synthesis of humulene (83) by the intramolecular cross-coupling of allylic bromide with alkenylborane is an example[278]. The reaction of vinyiborane with vinyl-oxirane (425) affords the homoallylic alcohol 426 by 1,2-addition as main products and the allylic alcohol 427 by 1,4-addition as a minor product[279]. Two phenyl groups in sodium tetraphenylborate (428) are used for the coupling with allylic acetate[280] or allyl chloride[33,28l]. 

It was claimed that the Z-form of the allylic acetate 430 was retained in homoallylic ketone 431 obtained by reaction with the potassium enolate of 3-vinylcyclopentanone (429), after treatment with triethylborane[282]. Usually this is not possible. The reaction of a (Z)-allylic chloride with an alkenylaluminum reagent to give 1,4-dienes proceeds with retention of the stereochemistry to a considerable extent when it is carried out at -70 C[283]. 

Treatment of (70a) with methanesulfonyl chloride in pyridine gives rise to vinylcylopropane (73) which can be converted back to the homoallylic alcohol (70a) under conditions similar to those used for converting cyclopropyl carbinol (69a) to the B-homo-7)5-ol (70a). 

In contrast to the behavior of homoallylic alcohol (70a) when treated with methanesulfonyl chloride is pyridine, heating A -19-methanesulfonate (68b) in pyridine gives the 5)5,19-cyclo-6-ene (72). Vinylcyclopropane (72) is inert to the conditions used for converting vinylcyclopropane (73) to the A ° -B-homo-7)5-ol (70a). The latter results are only consistent with the existence of two discrete isomeric carbonium ion intermediates which give rise to isomeric elimination products. °... 

Two approaches for the synthesis of allyl(alkyl)- and allyl(aryl)tin halides are thermolysis of halo(alkyl)tin ethers derived from tertiary homoallylic alcohols, and transmetalation of other allylstannanes. For example, dibutyl(-2-propenyl)tin chloride has been prepared by healing dibutyl(di-2-propenyl)stannane with dibutyltin dichloride42, and by thermolysis of mixtures of 2,3-dimethyl-5-hexen-3-ol or 2-methyl-4-penten-2-ol and tetrabutyl-l,3-dichlorodistannox-ane39. Alternatively dibutyltin dichloride and (dibutyl)(dimethoxy)tin were mixed to provide (dibutyl)(methoxy)tin chloride which was heated with 2,2,3-trimethyl-5-hexen-3-ol40. 

Both allylstannane transmetalation and thermolysis of homoallyl stannoxanes have been used to prepare 2-butenyltin halides as (E)j(Z) mixtures44-45. The reaction between 2-butenyl-(tributyl)stannane and dibutyltin dichloride initially provides dibutyl(l-methyl-2-propenyl)tin chloride as the kinetic product by an SE2 process, but this isomerizes under the reaction conditions to give a mixture containing the (Z)- and (E)-2-butenyl isomers46. 

Transmetalation to give l-methyl-2-propenylaluminum followed by isomerization to 2-butenyl isomers may be involved in reactions between aldehydes and 2-butenyl(tributyl)-stannane induced by aluminum(III) chloride in the presence of one mole equivalent of 2-propanol. Benzaldehyde and reactive, unhindered, aliphatic aldehydes give rise to the formation of linear homoallyl alcohols, whereas branched products are obtained with less reactive, more hindered, aldehydes66,79. 

Treatment of allyl bromides with the complex obtained from tin(II) chloride and the disodium salt of diethyl 2,3-dihydroxybutanedioate gives an intermediate which reacts with aldehydes to provide homoallylic alcohols with 50-65% ee. Lower enantiomeric excesses were obtained with bulky aldehydes and for allylstannanes with y-substituents. Pentacoordinated allyltin complexes may be involved97. 

The complex 8, formed by the addition of 2-propenylmagnesium chloride to 7, adds to aromatic aldehydes, 1-alkanals, a-branched and unbranched alkanals uniformly from the 7 c-face leading to hoinoallylic alcohols with 88-94% ee35 (Method A). After hydrolytic workup, both components can be recycled. Allyl complexes 10, generated from 9, prefer 67-attack and lead to the ent-homoallylic alcohols with excellent enantioselectivity36 (Method B) (Table 8). 

One of the most gentle methods for the generation of reactive allylmetallic reagents was introduced in 1977 by Hiyama and Nozaki1,2,3,33. By the action of two equivalents of chromi-um(II) chloride on allylic halides in tetrahydrofuran at 0°C in the presence of a carbonyl compound, reductive coupling with the formation of a homoallylic alcohol takes place. 

Indium-mediated allylation of an unreactive halide with an aldehyde132 was used to synthesize an advanced intermediate in the synthesis of antillatoxin,133 a marine cyanobacteria (Lyngbya majus-cula) that is one of the most ichthyotoxic compounds isolated from a marine plant to date. In the presence of a lanthanide triflate, the indium-mediated allylation of Z-2-bromocrotyl chloride and aldehyde in saturated NH4C1 under sonication yielded the desired advanced intermediate as a 1 1 mixture of diastereomers in 70% yield. Loh et al.134 then changed the halide compound to methyl (Z)-2-(bromomethyl)-2-butenoate and coupled it with aldehyde under the same conditions to yield the desired homoallylic alcohol in 80% yield with a high 93 7 syn anti selectivity (Eq. 8.55). 

Mg. Li and co-worker first reported magnesium-mediated Barbier-Grignard allylation of benzaldehyde in water (Eq. 8.73).172 Recently, a study was completed in which some water-tolerant allylating agents were prepared in situ from allylmagnesium chloride and various metallic salts reacted with aldehydes in THF-FLO to afford the desired homoallylic alcohols.173... 

In support of a radical pathway for such reactions, both cyclopropylcarbinyl bromide and iodide gave rise to appreciable homoallylic substitution product with the foregoing metallostannanes. In contrast, the corresponding chloride and tosylate gave only the unrearranged product. 

Reactions of Allylation and Propargylation Allylation of prochiral and chiral nitrones (292) with allylmagnesium chloride leads to homoallylic hydroxylamines (416), which via an iodo cyclization step are converted to 5-(iodomethyl)isoxazolidines (417) (Scheme 2.186) (202, 213, 666-668). 

Recently, Oshima et al. developed the conversion of acid chlorides into the corresponding homoallylic alcohols catalyzed by in r(/ -prepared hydridozirconium allyl reagents (Scheme 41),147 147a The proposed mechanism suggests an initial hydride transfer from the zirconocene crotyl hydride species, in equlibrium with its Cp2Zr(l-alkene),147a to the acid chloride with subsequent allylation to afford the corresponding homoallylic alcohols. 

Starting from 2,4,6-octatriene and pivaldehyde, the conjugated homoallylic alcohol 8 is obtained as the sole product. Cycloheptatriene-derived complexes react with aldehydes and C02 to afford mixtures of the isomeric 1,3- and 1,4-cycloheptadienyl carbinols or acids, respectively. Interestingly, analogous reactions with methyl chloroformate or dimethyl carbamoyl chloride produce the conjugated dienyl ester 9 or amide 10 as unique products [19,20]. 

Bis(homoallylic) alkoxides also undergo this 3-cleavage. The substrates (1) are available by reaction of a methyl carboxylate with 2 equiv. of allyl- or methallyl-magnesium chloride. The alcohols when heated at 80° in a slurry of KH in HMPT are converted into 3.7- and a,3-unsaturated ketones (2 and 3) in 75-85% yield. 

Hydrozirconation of monosubstituted allenes offers easy access to allylzircono-cene chlorides, which react with carbonyl compounds to afford homoallylic alcohols in a highly regio- and stereoselective manner (Scheme 16.68) [73-75],... 

Homoallylic amines result from the reaction of aldimines, previously activated by boron trifluoride etherate, with allylic bromides in the presence of chromium(II) chloride, e.g. equation 68194. 

The involvement of at least three different forms of the seleniranium ion intermediate, i.e. tight and solvent-separated ion pairs and free ions, has been invoked also to rationalize the different chemical behavior observed in the addition of benzeneselenenyl chloride to bicyclo[2.2.1]hepta-2,5-diene (49) in methanol and in methylene chloride140. As stressed by the authors, the addition of benzeneselenenyl chloride to 49 shows a number of interesting trends. Four products (151-154), all resulting from homoallylic attack, were isolated from the reaction carried out in methanol (equation 131). Furthermore, it... 

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