Acyclic 5-hydrogen abstraction

To summarize under favorable conditions the acidity of a-hydrogens facilitates the generation of a-sulfoxy and a-sulfonyl carbanions in thiirane and thiirene oxides and dioxides as in acyclic sulfoxides and sulfones. However, the particular structural constraints of three-membered ring systems may lead not only to different chemical consequences following the formation of the carbanions, but may also provide alternative pathways not available in the case of the acyclic counterparts for hydrogen abstraction in the reaction of bases. 

Alkenes. When the substrate molecule contains a double bond, treatment with chlorine or bromine usually leads to addition rather than substitution. However, for other radicals (and even for chlorine or bromine atoms when they do abstract a hydrogen) the position of attack is perfectly clear. Vinylic hydrogens are practically never abstracted, and allylic hydrogens are greatly preferred to other positions of the moleeule. Allylic hydrogen abstraction from a cyclic alkenes is usually faster than abstraction from an acyclic alkene. ... 

Photooxygenation of trisubstituted acyclic 11-13 and cyclic 14 and 15 alkenes illustrates impressively a strong preference for hydrogen abstraction on the less substituted side of the double bond. 

Irradiation of alkyl hypochlorites gives chloroalcohols formed by intramolecular hydrogen abstraction. This reaction has been observed with simple acyclic hypochlorites (210) and in the steroid series (211). 

Sequences in which addition precedes cyclization are not as straightforward to conduct as the reverse however, they are very important because a net annulation results (that is, a new ring is formed by the union of two acyclic precursors in one experimental step). The intermediate radical is differentiated from the other radicals provided that the cyclization reaction is rapid, but it can be difficult to differentiate the initial radical from the final radical. As illustrated in Scheme 57, this is particularly true in the tin hydride method because many different types of radicals react with tin hydride at similar rates. Reaction of (69) under standard radical addition conditions produces (70), which results from a sequence of addition/cy-clization/addition.233 That the last C—C bond is formed actually results from a lack of selectivity the initial and final radicals are not differentiated and they must undergo the same reaction. Of course, this lack of selectivity is of no consequence if the product contains the desired skeleton and the needed functionality for subsequent transformations. Such sequences are very useful for forming three carbon-carbon bonds, and they can also be conducted by Barton s thiohydroxamate method.234 Structural modifications are required to differentiate the initial and final radicals, and, as illustrated by the conversion of (71) to (72), phenyl groups can provide the needed differentiation (probably by retarding the rate of addition more than they retard the rate of hydrogen abstraction). Clive has demonstrated that phenyl-substituted vinyl radicals also provide the needed selectivity, as illustrated by the second example in Scheme 57.233... 

Reid DL, Armstrong DA, Rauk A, Nese C, Schuchmann MN, Westhoff U, von Sonntag C (2003) H-atom abstraction by C-centered radicals from cyclic and acyclic dipeptides. A theoretical and experimental study of reaction rates. Phys Chem Chem Phys 5 3278-3288 Roberts BP (1996) Understanding the rates of hydrogen abstraction reactions empirical, semi-em-pirical and ab initio approaches. J Chem Soc Perkin Trans 2 2719-2725 Russell GA (1973) Reactivity, selectivity, and polar effects in hydrogen atom transfer reactions. In Kochi JK (ed) Free radicals. Wiley, New York, pp 275-331 Russo-Caia C, Steenken S (2002) Photo- and radiation-chemical production of radical cations of methylbenzenes and benzyl alcohols and their reactivity in aqueous solution. Phys Chem Chem Phys 4 1478-1485... 

In trisubstituted alkenes with the cis alkyl groups highly crowded, the site selectivity (Sec. II.C) does not apply. In those cases, usually only one allylic hydrogen is available in the more crowded side, not sufficient to stabilize the proper transition state that could produce syn products. Instead, the major product is now produced by abstraction of the allylic hydrogen in the less substituted side of the double-bond anti selectivity [69], These results are summarized in Scheme 9. Photo-oxygenation of trisubstituted acyclic 15-17 [69] and cyclic 18 [70] and 19 [9] alkenes illustrates impressively a strong preference for hydrogen abstraction on the less substituted side of the double bond. 

Sakamoto and co-workers have explored a very interesting photochemical method for the preparation of p-lactams [95JOC7088], The reaction proceeds through a hydrogen abstraction from achiral acyclic monothioimide 11. When the photolysis is conducted in the solid state, absolute asymmetric induction takes place and the lactam 13 is produced with low enantiomeric excess. 

Scheme 10. Preference for d-hydrogen abstraction in acyclic molecules.

Absolute asymmetric synthesis using the chiral crystal environment photochemical hydrogen abstraction from achiral acyclic monothioimides in the solid state. Journal of Organic Chemistry, 60 (22), 7088-7089 ... 

One of the first examples of 8-hydrogen abstraction in acyclic ketones was the photocyclization of P-alkoxy ketones, in particular of P-ethoxypropiophenone (34), to the corresponding furanol derivatives 37 (Scheme 8.10). It was revealed that formation of enol 36 as well as a reversion to the starting ketone occur by 1,4-hydrogen transfer from the 1,5-biradical 35 causing the lower quantum efficiency for cyclization [12]. 

Lewis has reported that y-hydrogen abstraction in polycyclic ketones is more rapid than in acyclic ketones 68> and concluded that the rate increases are due to the increased number of frozen C—C bonds in the reactant. His measured activation parameters certainly support this interpretation. 

The lifetimes t of unfavorable conformations are determined by whatever decay reactions — physical and chemical — are available to each conformer. The decay rates r/1 of favorable conformations include rates of hydrogen abstraction. Quantum yields for hydrogen abstraction are determined by the relative rates of hydrogen abstraction and of decay, no matter what conformers they arise from. The type II reaction of acyclic ketones falls into this general class. The unit quantum yield for triplet state y-hydrogen abstraction in many ketones indicates that conformational change is faster than hydrogen abstraction which, in turn, is faster than any other form of decay. 

Acyclic enamines give diazetidines with dimethyl diazenedicarboxylate, e.g., formation of 9. when hydrogen abstraction and ene reaction can be suppressed18, but from the less nucleophilic A -vinylpyrrolidinone the oxadiazine 10 is obtained16. 

Rothenberg, G., Sasson, Y. Cyclic vs. acyclic allylic hydrogen abstraction an entropy motivated process Tetrahedron 1998, 54, 5417-5422. 

The Norrish type I reaction of acyclic and cyclic ketones in solution typically results in recombination, decarbonylation and disproportionation (hydrogen abstraction) products.903 For example, irradiation of di-tert-butyl ketone (265) in hexane solution provides nearly exclusively decarbonylation products from both the singlet and triplet states (>90% chemical yield), whereas the carbonyl group-containing products are produced only in traces (Scheme 6.111).922 923... 

Norrish Type I cleavage reactions dominate in the gas phase photochemistry of many acyclic aldehydes and ketones, whereas in the liquid phase this process is less common and alternative pathways (ii, iii, v) dominate. When no suitable C-H bonds are present to allow hydrogen abstraction reactions, however, this process will also constitute an important synthetic method for the cleavage of a-C-C bonds in solution. One important subsequent reaction of the resulting acyl and alkyl radicals is carbon monoxide formation and radical combination. Overall CO extrusion results which represents a versatile method for the formation of C-C single bonds from ketones. When cyclic substrates (cycloalkanones but not conjugated cycloalkenones which exhibit a different photochemistry) are used, ring... 

In comparison to stereoselective hydrogen abstraction, diastereoselective C-C bond formation of acyclic radicals often occurs with higher levels of asymmetric induction. 

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