4- Butenyl radicals, cyclization

The formation of a three-membered ring by 3-exo trig cyclization of a 3-butenyl radical, even though kinetically allowed, is highly unfavorable because the opening... 

Returning to the discussion of the behavior of the 5-hexenyl radical (Section III.l.B), if the model proposed by Beckwith (which involves the necessity for the radical to lie above the plane of the double bond) is accepted, it is clear that this will become more and more difficult as the chain length shortens. In fact, cyclized products are not observed with the 4-pentenyl and 3-butenyl radicals when these are generated from the corresponding bromides under the conditions used successfully with the hexenyl bromide (Scheme 13). 

The possibility of cyclization of 3-butenyl radicals is well established, giving apparently only Cy 3, the methylcyclopropyl radicals (9.4 X 10 sec at 40°C) but the opening of the methylcyclopropyl radical is faster (1.3 X 10 sec at 25°C ) so that the cyclization process is essentially reversible K = 1.3 X 10" at 25°C, statistically corrected for A and This is inferred mainly from products which appear to result from 1,2-vinyl migration (Scheme 17) 3.436-448... 

A very important and much studied case of intramolecular addition of a 3-butenyl radical is that of the special case 18 this gives high yields of cyclized (Cy 3) products (the so-called norbornenyl-nortricyclyl rearrange-This subject has been extensively covered by Wilt and will be not discussed here except for new results of particular relevance. 

This preparatively valuable endoperoxide-diepoxide transformation has recently been employed in a number of interesting synthetic problems, but mechanistic questions remain unanswered, although a concerted process for the bis addition of the two alkoxyl radicals rather than a stepwise intramolecular addition has been retained.Of course the possibility of a reversible cyclization-opening process, analogous to the one observed with the 3-butenyl radical (Section V.2.B), may be considered, particularly if the oxyranylalkyl radical is stabilized. ... 

It was proposed that the transition state requires approach of the radical directly above the site of attack and perpendicular to the plane containing the carbon-carbon double bond. An examination of molecular models shows that for the 3-butenyl and 4-pentenyl radicals (16, =1,2) such a transition state can only be reasonably achieved in < Xf>-cyclization (i.e. 16—> 15). With the 5-hexcnyl and 6-heptenyl radicals (16, w=3,4), the transition state for exo-cyclization (16- 15) is more easily achieved than that for enc/o-cyclization (i.e. 16 — 17). 

The radical cyclization test has been applied and although 2-(3-butenyl)phenyl halides give little if any cyclization, substituents that are expected to increase the rate of cyclization to around 109s 1 do give some cyclic product.14... 

The parent compound, 69, has been synthesized and characterised <2003ZFA1475>. 4-Chloro-hepta-l,6-diene was reacted with Mg. No Grignard rearrangement was noticed but instead the Grignard reagent was converted into l-allyl-3-butenylphosphonous dichloride by reaction with PC13. Reduction with LiAlH. produced l-allyl-3-butenyl-phosphane. Radical-initiated cyclization led to the product, l-phosphabicyclo[3.3.0]octane. Four derivatives were similarly prepared and characterized (70-73). Compound 74 was similarly prepared via a radical reaction < 1997PS(123)141 >. 

Butenyl,Pentenyl,Heptenyl and Other Radical Cyclizations 785... 

Intramolecular cyclization of the chiral oxime ether 993 in the presence of isopropyl iodide and triethylborane affords the 3,4,5-trisubstituted tetrahydropyran-2-one 994 in poor yield but with good diastereoselectivity (Equation 388) <2003JOG5618>. Similarly, a triethylborane-induced atom transfer radical cyclization of 3-butenyl 2-iodoacetate leads to 4-(iodomethyl)tetrahydropyran-2-one. Higher yields are achieved when conducting the reaction at lower concentrations (Equation 389) <2000JA11041 >. 

In the second approach shown in Scheme 10, the vinyl radical was generated by addition of a tributyltin radical to the terminal acetylene group. In this case, the allyl radical formed in the first cyclization reaction might provide a large steric bias during the second ring closure and could thus impose a better stereoselectivity than in the first approach. The synthesis commenced from the same starting material 77 as in the synthesis of 78. The butenyl chain was attached first and the butynyl chain was introduced second to provide ketoester 83. 

Because of the rather fast cyclization 131 - 132 (kj = 1 10s s"1 at 25 °C)90) this reaction or the cyclization of the related l-methyl-5-hexenyl radical 134 91) and the o-(3-butenyl)phenyl radical 135 92> is often used as a radical clock in reactions possibly passing through radical intermediates 93... 

A mechanistic study concerning the variation of the product ratio in reactions of different o-(3-butenyl)halobenzenes (Hal = F, Cl, Br and I), and of 6-bromo-l-hexene with different alkali metals (Li, Na, K) in ammonia/tert-butyl alcohol solution 110) is related to the problem of anion versus radical cyclization as outlined in this chapter. 

Ring expansion of a bicyclo[5.1.0]octan-l-ol 90 bearing a butenyl substituent at C6 was catalyzed by manganese(III) tris(2-pyridinecarboxylate) [Mn(pic)3]. In the presence of an alkene, the initial bicycloalkoxyl radical ring expanded to give a 3-oxocyclooctyl radical which cyclized and underwent addition to the alkene, finally affording a substituted bicyclo[6.3.0]un-decan-3-one, e.g. 91. 

Further studies on the Cj + Cj route to rose oxide (909) mentioned in Vol. 4 (p. 565, Ref. 773) include the radical addition of 3-methyl-3-butenyl acetate to 3-ethoxy-3-methylbutanal. This led to 40% of the ketone 926, which can be converted to rose oxides (cis/trans 9 1) by reduction (NaBH4), hydrolysis, and acid cyclization. °° Russian workers have examined (and with variously substituted homologs) the reaction between 3-methylbutanal (82) and 4,4-... 

Electron transfer to 2-(3-butenyl)cyclopentanone using zinc-chlorotrimethylsilane generates a radical that cyclizes stereoselectively in a 5-exo mode to cfv-annulated cyclopentanols31. Similar to the cyclizations of the 2-(3-butenyl)cyclopentyl radical, a strong preference for the 1,5-ris-substituted diastereomer is observed. 

The angular triquinane ( )-6-silphiperfolcne is prepared by a related tandem radical cyclization sequence92,93. The precursor (4i /S)-3-(3-butenyl)-4-[( )-3-bromo-2-methyl-2-butenyl]-4-mcthyl-2-cyclopentenone is rapidly assembled (three steps) from 3-ethoxy-2-cy-clopentenone in 45 % overall yield. Radical cyclization of the precursor provided a 3 1 mixture of isomers in 66% yield. In the major stereoisomer, the methyl group is orientated / , opposite to that required in the target product. 

Butenyl cyclizations are in principle fast reactions proceeding in a 3-exo mode. The rate constant for this type of cyclization is usually in the range of 10" -6 X 10 s. Still, the preparative usefulness of this transformation has remained rather limited because the ring opening of the product cyclopropyl carbinyl radical is usually much faster (A = 10 — 10 s" ) as shown in Scheme 1 [3]. 

The preponderant formation of the 1,5-trans products 25 and 27 is totally unexpected, especially since other structurally related radicals (e.g., 28a and 2Sb) and their carbocyclic analogs give a mixture with mostly 1,5-ctj products [3, 5, 12-15]. If one assumes that the dioxane ring maintains the chair conformation and that the bulky phenyl and butenyl groups occupy equatorial orientations, then the 1,5-trans product can only be rationalized by a boat-like cyclization transition state depicted by structure 34 in Fig. 7.9, in which the pseudoaxial radical attacks the C=C bond in the pseudoequatorial butenyl side chain. The original preference... 

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