Radical allylation approach

The modification of [T-amino acids by a-selenylation and then free radical allylation leads to the formation of (A-amino acids bearing an a-allyl group (Scheme 12). Hanessian and co-workers 22 initially used this approach to produce p2 3-amino acids which were then subjected to suitable coupling procedures. Interestingly, the coupling method chosen made use of PyBOP and hence demonstrates that other peptide coupling procedures can be used in the synthesis of (3-peptides. 

S.J. Danishefsky and co-workers reported the total synthesis of pentacyclic sesquiterpene dilactone, merrilactone A. ° In their approach, they utilized Keck s radical allylation method to achieve the required chain extension. This sidechain was later used to construct one of the cyclopentane rings of the natural product. 

Excellent stereocontrol is observed in reactions of four-membered rings. For instance, methyl a-allylpenicillinate 1,1-dioxide is formed as a single isomer via radical allylation (Scheme 1, Eq. 1.1) [3]. Interestingly, the yff-isomer was obtained when a gew-dibromide was used as radical precursor (Scheme 1, Eq. 1.2). In this approach, the stereochemistry is established during the reduction of the intermedi-... 

This free-radical acylation approach is extended for the synthesis of a-keto esters and ketones using phenylsulfonyl methoxycarbonyl oxime ether 5 [23] and bis-methanesulfonyl oxime ether 6, respectively (Scheme 6) [24], 5 is more reactive and effective than 2b. For instance, radical reaction of tert-butyl iodide with 5 gave tert-butyl oxime ester in 65% yield, whereas the use of 2b gave the corresponding tert-butyl oxime ether in 15% yield. In free-radical-mediated ketone synthesis via a sequential radical acylation approach, 6 is used as a carbonyl equivalent geminal radical acceptor. This method works well with primary alkyl iodides but somewhat less efficiently with secondary iodides and can be applied to prepare unsymmetrical acyclic ketones as well as cyclic ketones. It is noteworthy that stable allylic and benzylic radicals react smoothly with 6. 

The second example in Table 5 shows the cyclization-carbonylation-allylation sequence, in which 5-hexenyl radical cyclization precedes CO trapping. Because of the nucleophilic nature of acyl radicals, in a mixed alkene system comprised of an electron deficient alkene and allyltin, they favor the electron deficient alkene first and the resulting product radical, which have an electrophilic character, and then smoothly add to allyltributyltin. This four-component coupling reaction provides a powerful radical cascade approach leading to y -functionalized, -unsaturated ketones, which are not readily accessible by other methods [52]. 

The first synthesis of the tetracyclic substructure ABCE was published by Hart et al. As illustrated in Scheme 26, the route includes (a) a new approach to substituted perhydroisoquinolines that features a stereoselective free radical allylation, (b) a Mitsunobu reaction using a new iV-acylsulfonamide (this step was completed with net retention of configuration), and (c) final preparation of a A. -azocine via an intramolecular iV-alkylation in high yield (the system has limited degrees of freedom due to the presence of the Z-alkene) [88]. 

Butler and co-workers have taken a unique approach to study the unimolecular dissociation of the vibrationally and rotationally hot allyl radical.150-152 They have examined the secondary C-H dissociation of the allyl radicals that are produced with high internal energies above the allyl dissociation thresholds in the primary photodissociation of allyl chloride and allyl iodide at 193 nm. The production of allene versus propyne (both at mass 40) from the secondary dissociation of the hot allyl radicals are... 

Zard and coworkers [32] reported a simple approach to create another group of natural products, namely the lycopodium alkaloids [15]. These authors first investigated the reaction of O-benzoyl-N-allylhydroxylamide 3-60 with tributyltin hydride and ACCN in refluxing toluene, which led (after formation of the N-radical 3-61 in a 5-exo-trig/5-exo-trig cyclization) to the undesired pyrrolidine 3-62 in 48% yield. Nevertheless, a small structural modification, namely the placement of a chlorine atom at the allyl moiety as in 3-63, induced a 5-exo-/G-endo- instead of the 5-exo-/5-... 

An alternative approach for determining the relative pi electronic stabilization of two torsional isomers utilizes a molecular dissection into two open shell radical fragments. This approach is illustrated by examining torsional isomerism in butadiene and 1,3,5-hexatriene. The ir MO s of the conformational isomers of 1,3,5-hexatriene can be constructed from the union of the n MO s of two formal allyl radicals. The two regiochemical modes of union of interest will be designated cis and tram ... 

In a rare example of the use of phenylselenides as radical precursors in the generation of alkene radical cations by the fragmentation approach, Giese and coworkers generated a thymidine C3/,C4/ radical cation by expulsion of diethyl phosphate. Trapping experiments were conducted with methanol and with allyl alcohol (Scheme 16), when nucleophilic attack was followed by radical cyclization [66]. 

Photo-polymerization was conducted at 254 nm under a modified fluorescent microscope. Allyl-oligonucleotides were employed with methylene blue as the free radical initiator for crosslinking. In the case of proteins, acryloyl streptavidin was first immobilized so that biotinylated proteins could be applied to the gel pad (Vasiliskov et al., 1999). One of the major drawbacks with the gel pad approach was that separate pads had to be manufactured instead of coating the enhre slide with the gel and then printing down the microarray. 

The combination of allylic amination, ring-closing metathesis, and a free radical cyclization provides a convenient approach to the dihydrobenzo[b]indoline skeleton, as illustrated in Scheme 10.10. The rhodium-catalyzed aUylic amination of 43 with the lithium anion of 2-iodo-(N-4-methoxybenzenesulfonyl)arrihne furnished the corresponding N-(arylsulfonyl)aniline 44. The diene 44 was then subjected to ring-closing metathesis and subsequently treated with tris(trimethylsilyl)silane and triethylborane to afford the dihydrobenzojhjindole derivative 46a in 85% yield [14, 43]. 

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