Radical stereoselectivity acylation

The acyl anion chemistry of acylzirconocene chlorides has also been applied to the stereoselective preparation of ( )-a,(3-unsaturated selenoesters and telluroesters (Scheme 5.35) [38]. Although no carbon—carbon bond was formed, this reaction reflects the synthetic interest in ( )-a,(3-unsaturated selenoesters and telluroesters, which are well-known precursors of acyl radicals and acyl anions, respectively. 

Radical cascades that feature a 7-exo acyl radical cyclization followed by a 6-exo or 5-exo alkyl radical cyclization proceed with very good yields and diastereoselectivities. Two examples are shown in Reaction (80), where treatment of 100 with E3B, air, and (TMS)3SiH provided the tricycle 101 in excellent yields as a single diastereomer. Interestingly, the bulky silyl ether moiety is not required to achieve stereoselectivity in this process. 

In any consideration of stereoselectivity in radical addition to acylic substrates, interpretation of the results is complicated by the knowledge that alkenes may be converted, at least in part, into their geometrical isomerides by traces of bromine (or of HBr, i.e. by Br, cf. p. 315). This may, however, be minimised by working at low temperatures, and by using a high concentration of HBr. Thus addition of liquid HBr at -80° to cis 2-bromobut-2-ene (67) was found to proceed with high TRANS stereoselectivity, and to yield (68) almost exclusively ... 

In recent years, the importance of aliphatic nitro compounds has greatly increased, due to the discovery of new selective transformations. These topics are discussed in the following chapters Stereoselective Henry reaction (chapter 3.3), Asymmetric Micheal additions (chapter 4.4), use of nitroalkenes as heterodienes in tandem [4+2]/[3+2] cycloadditions (chapter 8) and radical denitration (chapter 7.2). These reactions discovered in recent years constitute important tools in organic synthesis. They are discussed in more detail than the conventional reactions such as the Nef reaction, reduction to amines, synthesis of nitro sugars, alkylation and acylation (chapter 5). Concerning aromatic nitro chemistry, the preparation of substituted aromatic compounds via the SNAr reaction and nucleophilic aromatic substitution of hydrogen (VNS) are discussed (chapter 9). Preparation of heterocycles such as indoles, are covered (chapter 10). 

Free-radical cyclization of phenyl selenide 15 to indolizidinone 16 represented a key step in the total synthesis of (—)-slaframine (equation 52). The two pairs of diastereomers were first separated and then hydrolyzed to the corresponding alcohols in 76% overall yield77. (TMS)3SiH-mediated acyl radical reactions from phenylseleno esters 17 have recently been utilized for the stereoselective synthesis of cyclic ethers78. In fact, the experimental conditions reported in equation 53 are particularly good for both improving cis diastereoselectivity and suppressing decarbonylation. 

Intramolecular addition of acyl radicals to enoates proceeds in high yields. The acyl radicals are generated conveniently from acyl selenides. The application of this methodology in the stereoselective synthesis of cis-2,5-disubstituted tetrahydrofuran-3-ones is illustrated [95TL31],... 

Also for stereoselective radical reactions such as radical additions or radical cyclizations, the camphor sultam 2 is suitable as an auxiliary (Scheme 7). The acyl radical which was gener-... 

Sc(OTf)3 also catalyzes acetalization reactions [47a,b], acylal formation [47c], /9-selective glycosilation reactions with thioglycosides [48], and acylation reactions of alcohols [49]. Guanidium formation reactions of carbodiimide with benzylamine [50], intermolecular stereoselective radical additions to A/-enoyloxazolidinones [51], and rearrangement of... 

This thioformylation reaction of alkynes gave only f-isomers and this poses an intriguing mechanistic issue. To account for the stereoselectivity, two isomerization mechanisms need to be taken into consideration one is ivZ-isomerization between the products induced by thiyl radicals and the other is the isomerization of a,) -unsaturated acyl radicals prior to H-abstraction, which is achieved via a-kete-nyl radicals (Scheme 4-9). Interestingly, some recent examples clearly show that a,)ff-unsaturated acyl radicals can rapidly interconvert. 

This review focuses on free radical-mediated stereoselective bond construction in which the carbonyl group plays a key role. Reaction at the carbonyl group as well as on carbons alpha and beta are described. The general reaction characteristics of these reactive intermediates are as follows. The acyl radicals are nucleophilic in character and thus they react easily with electrophilic acceptors. On the other hand, radicals on carbon alpha to the carbonyl are electrophilic in nature and their reactivity matches with nucleophilic partners. The majority of reactions at carbon beta to the carbonyl are in a, -unsaturated systems and in these the beta carbon is electrophilic. 

Few examples exist in the literature concerning the stereoselective addition of acyl radicals to a radical acceptor in an acyclic manner. Equation (13.1) shows the efficient 1,2-asymmetric induction in the addition of aliphatic or aromatic acyl radicals to chiral acyclic alkenes 1 [7]. The corresponding a-hydroxy ketones 3 were produced with high syn selectivity (Table 13-1). This acyl radical addition is very exothermic, and it is hypothesized that Hammond s postulate can be invoked to predict a transition state that is very close in energy to the starting alkene 1. The X-ray structure of 1 was then used to rationalize the stereochemical outcome of this radical addition by determination of the least sterically hindered path for the approaching radical. 

Phenol-ketone novolacs 1487, 1488 Phenol-nitrile complexes 377 Phenol radical cations 1101 fragmentation of 289-291 Phenols—see also Biphenols, Bis-phenols, Hydroxybenzenes, Polyphenols acidities of, gas-phase 310-312 acylation of 629-632, 933, 934 Lewis acid catalyzed 631 montmoriUonite-catalyzed 632 pyridine-catalyzed 631 adsorption of 944 alkylation of 606-629, 941 Brdnsted acid catalyzed 612 Lewis acid catalyzed 607-611 solid acid catalyzed 612-621 stereoselective 621-626 under supercritical conditions 621 as antioxidants 139-143, 840-901 ort/io-substituted 845 thermochemistry of 139, 140, 179 autoxidation of 1118, 1119 bromination of 649-651 jr-cation interaction of 322 chlorination of 649 comparison with isoelectronic methyl, amino and fluoro aromatic derivatives 226... 

Hydroxy sulfones can be easily transformed into derivatives for radical-mediated reactions such as thiobenzoates,220 xanthates,221,222 selenoben-zoates,221,222 and thionocarbonates.221,222 These substrates may be used in subsequent stereoselective syntheses of alkenes by free radical methods. Methyl xanthates usually give the best results in the olefination reaction, typically using O-acyl A - It y d roxy- 2 - thiopy ri d o n e under visible light irradiation. Alternatively, diphenylsilane in combination with radical initiators such as Et3B/02, benzoyl peroxide, or AIBN may also be used (Eq. 127).221 222... 

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