Free-radical allylation

Free radical allylation free radical reduction (homogeneous)... 

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. 

Allyltin reagents supported on polymer underwent free radical allylic transfer with a marked preference for electron-poor carbon radicals598. The fluorous method developed by Curran and coworkers has recently been successfully extended to four-component radical reactions using fluorinated allyltin reagents599. 

Enholm EJ, Gallagher ME, Jiang S, Batson WA, Free radical allyl transfers utilizing soluble non-cross-linked polystyrene and carbohydrate scaffold supports, Org. Lett., 2 3355-3357, 2000. 

A variety of carbohydrate-based acids were then prepared via the free radical allylation route as shown below in Table 3 (18). 

The following propagation steps show how a mixture of products results from the free-radical allylic bromination of but-l-ene. 

Step 1 Free-radical allylic substitution (Mechanism 15-2) R—H + Br2 R—Br + HBr... 

C-Glycosides. Thiophenyl glycosides undergo ready free-radical allylation with allyl- or methallyltri- -butyltin. Thus the L-lyxose derivative 1 reacts with allyltri-/ -butyltin under photochemical initiation to give 2 and 3 in the ratio 90 10. The reaction... 

Enholm [12] has carried out free radical allyl transfer reactions using a non-cross-linked polystyrene, soluble polymer 77. Model reactions of bro-mo ester 78 with allyltin reagents gave products 79 and 80 in excellent yield (Scheme 17). 

Enholm et al. [172] also examined free radical allylations of carbohydrate linked bromo esters. The D-xylose-derived ester 267 was reacted with allytributyltin and ZnCl2 as a Lewis acid to give the ester 268 (Scheme 10.87). The diastereoselectivity and yield of the allylation reaction were high. 

SCHEME 10.87 The stereochemical course of free radical allylations can be influenced through incorporation of sugar-derived auxiliaries. 

SCHEME 10.88 Sugar-directed asymmetric free radical allylations can proceed on a solid support. 

Allylstannanes work as allylating reagents under free-radical reaction conditions. Free-radical reactions have several advantageous features in organic synthesis -neutral reaction conditions, compatibility with Lewis acids, and no need to protect reactive functional groups such as hydroxy and amino groups. In these days, therefore, free radical allylation procedures have been widely used in organic synthesis and several reviews on free radical reactions are available [94]. 

Exposure of an allylstannane to halopyranoses in the presence of AIBN enables access to the corresponding allyl adducts [95] this procedure is useful for C-allyl glycosidation [96]. To enhance the practical utility of C-glycosidation, the effect of conformational restriction on a- and / -selectivity was studied in free-radical allylation at the anomeric positions of phenylselenoxylose derivatives of fixed conformation (Scheme 12.37) [97]. Treatment of a phenylthionocarbonate of 2 -deoxynucleo-side [98] and an iodopyrrolidine ]99] to allyltributyltin/AIBN resulted in substitution of the allyl moiety. 

It has been observed that addition of Lewis acids to the free radical allylation improved the chemical yield [101]. When substrates with a chiral auxiliary were subjected to free radical allylation in the presence of a Lewis acid, the desired allylated products were obtained with high stereoselectivity [94 d]. In these reactions the Lewis acid plays a pivotal role in fixing the conformation of radical intermediates. Recently Sibi indicated that an elevated reaction temperature accelerated inversion of the stereochemistry of the radical-centered carbon giving rise to greater diastereoselectivity (Scheme 12.39) [102]. When enantiomerically pure Lewis acids were employed as chiral auxiliaries enantioselective free radical allylation of sulfones [103] and oxazolidinones [104] were realized. In the latter reaction two contiguous chiral centers were generated successfully in a single operation with excellent stereoselectivity via tandem C-C bond formation both enantiomers can be se-... 

Formation of isomers in free-radical allylic substitution is a general rule. In this case, abstraction of a hydrogen atom from C4 of the parent molecule leads to the formation of a delocalized allylic radical, with spin density distributed between two carbon atoms C-4 and C-6. Then this radical abstracts the bromine atom from NBS and adds it to one or the other position (Fig. 8) ... 

The inevitable formation of isomers should be taken into account when planning syntheses of PCA involving free-radical allylic substitution. 

Allyltributyltin (5) is the most commonly used reagent for carrying out allylation reactions via a free radical fragmentation process [5]. Keck reported the first practical use of allyltributyltin for free radical allylation reactions in 1982 in the context of a synthesis of perhydrohistrionicotoxin [6]. Heating bromide 4 with allyltributyltin in the presence of AIBN as a radical initiator gave the allylated derivative 6 (Scheme 3) in high yield with complete control of stereochemistry. Similar transformations had proven to be very difficult by standard ionic reactions. 

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]. 

Conjugare is a Latin verb meaning to link or yoke together, and allylic carbocations, allylic free radicals, allylic anions, and conjugated dienes are all examples of conjugated systems. In this chapter weTl see how conjugation permits two functional units within a molecule to display a kind of reactivity that is qualitatively different from that of either unit alone. 

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