Ethers, methyl thermolysis

Stereoselective aldol reactions of a-methyl aldehydesThe lithium enolatc of this ethyl ketone (1) reacts with various a-methyl aldehydes to form aldols, which after protection as silyl ethers and thermolysis (500 ) were isolated as the a, / -unsaturated ketones 2 and 3. The diastcrcoselectivity is highly dependent on the R group. Thus... 

Because di-/ fZ-alkyl peroxides are less susceptible to radical-induced decompositions, they are safer and more efficient radical generators than primary or secondary dialkyl peroxides. They are the preferred dialkyl peroxides for generating free radicals for commercial appHcations. Without reactive substrates present, di-/ fZ-alkyl peroxides decompose to generate alcohols, ketones, hydrocarbons, and minor amounts of ethers, epoxides, and carbon monoxide. Photolysis of di-/ fZ-butyl peroxide generates / fZ-butoxy radicals at low temperatures (75), whereas thermolysis at high temperatures generates methyl radicals by P-scission (44). 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

Two approaches for the synthesis of allyl(alkyl)- and allyl(aryl)tin halides are thermolysis of halo(alkyl)tin ethers derived from tertiary homoallylic alcohols, and transmetalation of other allylstannanes. For example, dibutyl(-2-propenyl)tin chloride has been prepared by healing dibutyl(di-2-propenyl)stannane with dibutyltin dichloride42, and by thermolysis of mixtures of 2,3-dimethyl-5-hexen-3-ol or 2-methyl-4-penten-2-ol and tetrabutyl-l,3-dichlorodistannox-ane39. Alternatively dibutyltin dichloride and (dibutyl)(dimethoxy)tin were mixed to provide (dibutyl)(methoxy)tin chloride which was heated with 2,2,3-trimethyl-5-hexen-3-ol40. 

Imanishi and coworkers reported that thermolysis of the benzyl methyl ethers 98 (or benzyl-phosphonium salts) leads to high yields of indoles 99 in the absence of strong base. In the case of the methyl ethers, heating in the presence of an acid and catalyst and PPhs presumably involves in situ formation of a phosphonium salt intermediate <96JCS(P1)1261,96H(42)513>. 

Further insight into the carbon-oxygen reductive elimination from Pt(IV) and the involvement of five-coordinate Pt(IV) intermediates has been provided recently. The first direct observation of high-yield C-0 reductive elimination from Pt(IV) was described and studied in detail (50,51). Carbon-oxygen coupling to form methyl carboxylates and methyl aryl ethers was observed upon thermolysis of the Pt(IV) complexes ( P2 )PtMe3(OR) ( P2 =bis(diphenylphosphino)ethane or o-bis(diphenyl-phosphino)benzene OR=carboxylate, aryl oxide). As shown in Scheme 47, competitive C-C reductive elimination to form ethane was also observed. 

Cycloheptanes.— The C-1—C-2 bond in -y-thujaplicin is essentially single, Co"-/3-thujaplicin-amine complexes have been described, and thermodynamic data on the U -/3-thujaplicin complex have been calculated. The biomimetic cyclization of the silyl enol ether (191) to karahanaenone (192), using methyl-aluminium bis(trifluoroacetate) is almost quantitative (192) is also synthesized by thermolysis followed by desilylation of the silyl enol ether (193) which is readily available from l-bromo-2-methyl-2-vinylcyclopropane and isobutyraldehyde. Dehalogenation of 3-bromo-l-iodo-3-methylbutan-2-one with Zn-Cu couple on alumina in the presence of isoprene yields (192) and minor amounts of the isomers (194) and (195) however, dehalogenation with Fc2(CO)9 favours (195). Acetolysis of karahanaenol tosylate yields anticipated p-menthane derivatives and no filifolene. ... 

Analogously, the thermolysis of the 1-methyl derivative in bis(2-methoxyethyl) ether (diglyme) at 160 °C for 30 minutes gave 2-methyIbicyclo[3.2.0]hept-l-ene (5) with 82% selectivity in 12% overall yield, while flash-vacuum pyrolysis (250°C/1 x lO -lO 3 Torr) gave 5 with 75% selectivity and 47-68% overall yield of volatile products.68... 

Even though the reagent usually cleaves methyl ethers, the corresponding ether 2b cun be obtained from lb in high yield. The ether is stable to acids, but an F.2 elimination to give the alcohol 3b is possible with base. The alcohol is an obvious precursor to a dibenzocyclooctadiene by dehydration, best effected by thermolysis... 

An enantioselective synthesis of (+)-estradiol has been accomplished from 1,3-dihy-drobenzo[c]thiophene 2,2-dioxide (306) by successive thermal S02-extrusion and cycloaddition (80HCA1703). Treatment of the optically active iodide (307) with two mole equivalents of the masked quinodimethane (306) in the presence of two mole equivalents of sodium hydride gave (308) as a 1 1 mixture of diastereoisomers. Thermolysis of this alkenic sulfone in 1,2,4-trichlorobenzene furnished the trans-anti-trans steroid (309) in 80% yield. Treatment of (309) with methyllithium gave the methyl ketone, which was subjected to a Baeyer-Villiger oxidation and then silyl ether-acetate cleavage to afford (-l-)-estradiol (310 Scheme 66). 

In another study several simple silenes RR Si=CH2 (R, R = Me, Vinyl etc.) were formed by laser-powered pyrolysis and were found to form linear polymers, in contrast to the usual behavior of silenes which yield cyclodimers when formed by conventional thermolysis techniques16. Reactions of the silenes in the presence of several monomers such as vinyl acetate, allyl methyl ether and methyl acrylate were also studied. Laser-induced decomposition of silacyclobutane and 1,3-disilacyclobutane gave rise to silenes and other oxygen-sensitive deposits17,18. 

Cyclization in phosphorus oxychloride of semicarbazides (79 X = NHR) yields aminooxadiazoles (81) whereas thermolysis leads to loss of ammonia (when X = NH2) and formation of an oxadiazolinone (80). Cyclization to aminooxadiazoles (81) occurs when thiosemicarbazides (82) are heated with an oxidizing agent such as lead oxide. This reaction has been widely applied to the synthesis of aminooxadiazoles, sometimes in low yields, and has been used to prepare 2-amino-l,3,4-oxadiazole (81 R1 =R2 = H). 5-Methyl ethers of thiosemicarbazides (82) cyclize, with loss of methanethiol, to aminooxadiazoles (81) on heating, but in PPA cyclization to 2-methylthio-l,3,4-oxadiazoles occurs. 

We shall conclude this Section with an example of a reaction that undergoes an extreme rate acceleration with an increase in solvent polarity. Thermolysis of a-chlorobenzyl methyl ether in a series of non-nucleophilic, non-HBD solvents shows rate variations up to 10, encompassing a range of 30 kJ/mol (7 kcal/mol) [112], This dramatic solvent effect is best explained by a mechanism involving ionization of the C—Cl bond to form an ion pair, followed by a nucleophilic attack by Cl on CH3 to give an aldehyde and chloromethane cf. Eq. (5-41). 

The rate constants of the unimolecular thermolysis of a-chlorobenzyl methyl ether to yield benzaldehyde and chloromethane [cf. Eq. (5-41) in Section 5.3.2] have been determined in supercritical 1,1-difluoroethane (tc = °C pc = 4.5 MPa). Near the... 

Subsequent studies on the thermolysis of 1,2,3-selenadiazole 16 (n = Z) in the presence of a variety of alkenes (methyl acrylate, acrylonitrile, methyl vinyl ketone, methyl methacrylate, methyl 2-butenoic acid, butyl vinyl ether, and 1-octene) also afforded cycloadducts 17, in 12-76% yield with the same regiochemistry as observed for cycloadditions with 14 <2000JOM488>. Analogous cycloadditions with methyl derivatives of 16 (n = Z) as well as 16 ( = 1, 3, and 4) and ethyl acrylate was also observed in yields of 35-76% (Table 1). In addition to the cycloadduct. 

The functionally and stereochemistry provided by aldehyde (100) have led to the use of the tandem Cope-Claisen rearrangement for the synthesis of estrone methyl ether (117) and steroid synthons. Thermolysis of triene (115 Scheme 8) provides aldehyde (116) as the major component of a 2/1 mixture ... 

Nonphotochemical cycloadditions of hexafluorothioacetone to alkenes (vinyl ethers, vinyl sulfides, " cyclohexene, and dimethyl maleate " ) have been observed, as illustrated for methyl vinyl ether. The formal addition of thiocarbonyl fluoride to tetrafluorethylene to give hexafluorothietane occurs on thermolysis at 600-700° (lO " mm) of a copolymer of the two components. " QO-Dimethyldithiooxalate undergoes a thermal cycloaddition to quadricyclane to give thietane 51a. ... 

---