Homoallyl substitutions

The thermal behavior of the closely related homoallyl-substituted azirine (182) has also been studied (77JA1871). Heating a solution of (182) in toluene gave 2-methylbiphenyl (183)... 

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. 

Cyclopropanes without electron-withdrawing substituents usually resist the attack of nucleophiles. Exceptions are strained systems and a-halo-substituted derivatives which undergo homoallylic substitution reactions.[l.l.l]Propellane structures, though usually formed only as intermediates, underwent addition of benzenethiol with cleavage of the central cyclopropyl bond. This addition possibly follows a radical chain mechanism. 

Storage Moisture-sensitive store in cool, dry place away from heat, sparks, open flame store under nitrogen keep tigthly closed Uses Reducing agent in silylation-reduction-allylation sequence of p-hydroxy esters to homoallylic-substituted 1,3-diols, in silylation-hydrosilation-oxidation of allyl alcohols to 1,3-diols, reduction of p-hydroxy ketones to anti-1,3 diols... 

Furthermore, N,N-disubstituted (2)-(2-en-4-ynyl)amines 221, possessing an allyl group, underwent the Au(I)-catalyzed cycloisomerization with a 1,3-allyl shift affording tri- and tetra-substituted pyrroles 222 (Scheme 8.83) [271]. This transformation allowed efHdent assembly of C2-homoallyl-substituted pyrroles bearing various... 

Further detailed studies on the kinetics of initiation by the Hoveyda-type catalysts revealed that the structure of the alkene influenced the mechanistic pathways by which the reaction proceeded. For particular alkenes, parallel mechanistic pathways were available [26-28]. The predominant mechanism involves dissociative or interchange IJ mechanisms. More hindered alkenes follow primarily a dissociative mechanism, while styrene is borderline where initiation proceeds, with contributions from both theand dissociative pathways. For smaller alkenes (i.e., those without allylic or homoallylic substitution), the two pathways were found to be operative. Substrate electronics also influenced pathway preference electron-rich or sterically permissive alkenes preferentially reacted via an interchange mechanism, while electron-poor and bulkier alkenes followed a dissociative pathway. 

Scheme 51 Hydroxycyclization of homopropargylic and homoallylic substituted 1,7-enynes...

The last group of reactions uses ring opening of carbonyl or 1-hydroxyalkyl substituted cyclopropanes, which operate as a -synthons. d -Synthons, e.g. hydroxide or halides, yield 1,4-disubstituted products (E. Wenkert, 1970 A). (1-Hydroxyalkyl)- and (1-haloalkyl)-cyclopropanes are rearranged to homoallylic halides, e.g. in Julia s method of terpene synthesis (M. Julia, 1961, 1974 S.F. Brady, I968 J.P. McCormick, 1975). 

Cyclopropyl methanols when treated with a combination of hydrogen fluoride, pyridine, potassium hydrogen fluoride, and diisopropylamine undergo fluonnation and rearrangement to give excellent yields of homoallylic fluorides Chlorobenzene substituted cyclopropyl methanols at low temperatures leads to ring expansion to give... 

An elegant application of the Vilsmeier reaction is the synthesis of substituted biphenyls as reported by Rao and RaoJ Starting with homoallylic alcohol 8, the biphenyl derivative 9 was obtained from a one-pot reaction in 80% yield ... 

Several examples for allylic reagents further substituted by heteroatoms are known. For example, a mixture of the l,l-dichloro-2-alkene and the l,3-dichloro-1-alkene leads to a homogeneous homoallylic alcohol17,18. 

Slightly more exotic carbon-centered nucleophiles can also participate in the ring-optening of epoxides. For example, the vinyl metallate 81, prepared by the treatment of the alkenyl acetal 86 with Schlosser s reagent, attacks mono-substituted epoxides 82 at the C-2 position to give the labile homoallyl alcohols 83 in fair to very good yields <96TET1433>. 

Additions of silylated ketene acetals to lactones such as valerolactone in the presence of triphenylmethyl perchlorate in combination with either allyltrimethylsilane 82, trimethylsilyl cyanide 18, or triethylsilane 84b, to afford substituted cyclic ethers in high yields have already been discussed in Section 4.8. Aldehydes or ketones such as cyclohexanone condense in a modified Sakurai-cyclization with the silylated homoallylic alcohol 640 in the presence of TMSOTf 20, via 641, to give unsaturated cyclic spiro ethers 642 and HMDSO 7, whereas the 0,0-diethyllactone acetal 643 gives, with 640, the spiroacetal 644 and ethoxytrimethylsilane 13b [176-181]... 

The present homoallylation with siloxy- and methoxy-substituted dienes may be of great synthetic use. The product 42 is easily converted to anti-5-phenyl-5-hydroxy-3-methylpentanal (Scheme 9) hence the diene 41f may be regarded as a synthetic equivalent of a bis-homoenolate of 3-methylbutanal, being capable of introducing 1,3-anti relationship between the methyl and hydroxy groups in the product. 

Table 5 summarizes the reactions of isoprene with aromatic aldehydes and unsaturated aldehydes. Salicylaldehyde provides the expected product as a cyclic boric ester derivative and shows apparently lower stereoselectivity, giving a mixture of 1,3-anti and 1,3-syn isomers in a ratio of 6 1 (run 1, Table 5). 2-Furfural reacts as usual and provides a 1,3-anti isomer as a single diastereomer in good yield (run 2). Unsaturated aldehydes, irrespective of their substitution patterns, undergo homoallylation selectively with excellent 1,3-anti selectivity, the geometry of the double bond of the starting aldehydes remaining intact (runs 3-5). 1,2-Addition to unsaturated aldehyde takes place selectively and no 1,4-addition is observed.

The zirconocene catalysts described above are very oxophilic, which provides several synthetically useful transformations. Oxygen substitution at the al-lylic or homoallylic position of an olefin substrate allows for excellent regio-and diastereocontrol in the ethyl magnesiation reactions of a-olefins and dienes [21]. When 29 is substituted with a hydroxyl group (29a), syn 30a is favored over anti in a 95 5 ratio, while substitution with OCH3 (29b) reversed the diastereoselectivity to 11 89 (Eq. 6). Use of THF in place of diethyl ether as the reaction solvent for the reaction of 29a lowered the overall diastereo-... 

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