Barton olefination

Barton-Kellogg Reaction (Barton Olefin Synthesis)... 

Stereoselectivity. See Asymmetric induction Axial/equatorial-, Cis/trans-, Enantio-, Endo/exo- or Erythro/threo-Selectivity Inversion Retention definition (e.e.), 107 footnote Steric hindrance, overcoming of in acylations, 145 in aldol type reactions, 55-56 in corrin synthesis, 261-262 in Diels-Alder cyclizations, 86 in Michael type additions, 90 in oiefinations Barton olefination, 34-35 McMurry olefination, 41 Peterson olefination, 33 in syntheses of ce-hydrdoxy ketones, 52 Steric strain, due to bridges (Bredt s rule) effect on enolization, 276, 277, 296, 299 effect on f3-lactam stability, 311-315 —, due to crowding, release of in chlorophyll synthesis, 258-259 in metc-cyclophane rearrangement, 38, 338 in dodecahedrane synthesis, 336-337 in prismane synthesis, 330 in tetrahedrane synthesis, 330 —, due to small angles, release of, 79-80, 330-333, 337... 

Barton olefinations, 35 Eschenmoser s sulfur extrusion, 59-60, 261 ThioacCtals. See 1,3-Dithianes 1,3-Dithiolanes ... 

The problem of the synthesis of highly substituted olefins from ketones according to this principle was solved by D.H.R. Barton. The ketones are first connected to azines by hydrazine and secondly treated with hydrogen sulfide to yield 1,3,4-thiadiazolidines. In this heterocycle the substituents of the prospective olefin are too far from each other to produce problems. Mild oxidation of the hydrazine nitrogens produces d -l,3,4-thiadiazolines. The decisive step of carbon-carbon bond formation is achieved in a thermal reaction a nitrogen molecule is cleaved off and the biradical formed recombines immediately since its two reactive centers are hold together by the sulfur atom. The thiirane (episulfide) can be finally desulfurized by phosphines or phosphites, and the desired olefin is formed. With very large substituents the 1,3,4-thiadiazolidines do not form with hydrazine. In such cases, however, direct thiadiazoline formation from thiones and diazo compounds is often possible, or a thermal reaction between alkylideneazinophosphoranes and thiones may be successful (D.H.R. Barton, 1972, 1974, 1975). 

Low-valent nitrogen and phosphorus compounds are used to remove hetero atoms from organic compounds. Important examples are the Wolff-Kishner type reduction of ketones to hydrocarbons (R.L. Augustine, 1968 D. Todd, 1948 R.O. Hutchins, 1973B) and Barton s olefin synthesis (p. 35) both using hydrazine derivatives. 

The reaction conditions applied are usually heating the amine with a slight excess of aldehyde and a considerable.excess of 2d-30hydrochloric acid at 100 °C for a few hours, but much milder ( physiological ) conditions can be used with good success. Diols, olefinic double bonds, enol ethers, and glycosidic bonds survive a Pictet-Spengler reaction very well, since phenol and indole systems are much more reactive than any of these acid sensitive functional groups (W.M. Whaley, 1951 J.E.D. Barton, 1965 A.R. Battersby, 1969). 

BARTON KELLOGG Olefinalion Olefin synthesis (letrasubsirtuted) from hydrazones and thiokelones via A -f,3,4-Ihiadiazollnes. 

Nitro-aldols, which are readily available (see Henry reaction Section 3.1), are converted into olefins via conversion of the hydroxyl group to the corresponding phenyl thiocarbonate ester and treatment with tin radical.158 The yield was not reported. Because the radical deoxygenation via thiocarbonate (Barton reaction) proceeds in good yield, the elimination of Eq. 7.115 might be good choice for olefin synthesis.159... 

The mechanism of the reaction is still obscure but our results are probably compatible with those of Pepper and Barton [23] who found that the rate of disappearance of unsaturation, when 1,3-diphenyl butene-1 (distyrene) reacted with perchloric acid, was of second order in olefin and in acid. Unfortunately they did not investigate whether any saturated products other than the cyclised dimer were formed, although they found some higher oligomers. 

The reduction of thiocarbonyl derivatives by EtsSiH can be described as a chain process under forced conditions (Reaction 4.50) [89,90]. Indeed, in Reaction (4.51) for example, the reduction of phenyl thiocarbonate in EtsSiD as the solvent needed 1 equiv of dibenzoyl peroxide as initiator at 110 °C, and afforded the desired product in 91 % yield, where the deuterium incorporation was only 48% [90]. Nevertheless, there are some interesting applications for these less reactive silanes in radical chain reactions. For example, this method was used as an efficient deoxygenation step (Reaction 4.52) in the synthesis of 4,4-difluoroglutamine [91]. 1,2-Diols can also be transformed into olefins using the Barton-McCombie methodology. Reaction (4.53) shows the olefination procedure of a bis-xanthate using EtsSiH [89]. 

The Barton-McCombie radical deoxygenation [221-223] (vide infra Section 3.2) has also been applied for transforming v/c-diols into olefins. Commercially available diphenylsilane and the easily formed dixanthates can be conveniently used for this purpose, as in the following example in the sugar series [224],... 

Interestingly, when a fi-substituted alcohol is used in the Barton-McCombie reaction and if a [3-elimination process occurs faster than the hydrogen transfer step, then the formation of a double bond is observed. We have just seen such an example with a dixanthate (see Section 3.1.3). Many others are known as in [3-hydroxy sulfides [231] and [3-hydroxysulfones [232,233] in a modified Julia synthesis of olefins. 

The best-known reactions belonging to this class are based either on the photo-NOCAS process [32] or on the photochemistry of Barton esters [69]. In the first case, a three-component reaction involving a cyanoarene, an olefin, and a nucleophile (usually the solvent) occurs. The reaction is generally initiated by a PET process between the aromatic and the olefin. The examples presented below are chosen from among the most representative and most recent. A typical reaction is illustrated in Scheme 3.26, where an enolized P-dicarbonyl compound acts as an added nucleophile. 

---