Dihydropyrans, rearrangement

Evidence for the two-step nature of the dihydropyran formation follows from the observation that both cis- and fraws-dibenzoylethene gave the same dihydropyran96, under conditions where cis-trans isomerism of the electrophilic alkene did not occur. On heating, the dihydropyrans rearrange into a mixture of the corresponding alkylated enamines (44 and 45) (Scheme 29). This is kinetically rather than thermodynamically controlled, since the equilibrium composition was obtained only after treatment with acid96, and can therefore be regarded as irreversible in an aprotic solvent (benzene) at 80°C. 

Dihydropyran rearrangements ( 1,4 rearrangements) proceed through the boatlike transition state, because the chairlike transition state which is constrained by a two carbon tether would lead to strained (Cl-cyclohexcne derivatives176. 

Due to the boat geometry, dihydropyran rearrangements usually require temperatures >190°C176. In common with acyclic Claisen rearrangements using the Ireland variation, considerably lower temperatures are necessary for the rearrangement of lactonic silyl enolates... 

In contrast to dihydropyran rearrangements, the rearrangement of 1,4-dioxins is believed to proceed via a chairlike transition state with the substituents in axial positions. Dihydro-1,4-dioxins 10 and 11, obtained by acid-catalyzed double-bond isomerization of 9. on heating in a sealed tube, undergo a sigmatropic shift to give dihydropyrans 12 and 13322 323. 

The l,4 5,6]-typc dihydropyran rearrangement of 1 leads to bicyclic compounds 2321. 

Dihydropyran rearrangements [ 1,4 rearrangements] are known to proceed through a boatlike transition state due to the short tethered chain (see p 3337). If a stereogenic center is attached to the new bond, the product stereochemistry is only governed by the substrate configuration, as shown by the synthesis of the precursor 8 of tetracyclic diterpene ( )-aphidicolin613,614. 

This methodology has been used for the synthesis of the C3-C14 segment 24 of the antitumor agent laulimalide 23 (Scheme 4.22) [35]. The constrained chiral BOX ligand 21c in combination with Cu(OTf)2 afforded dihydropyrane 6f by a cycloaddition reaction in good yield and ee this was converted to the C3-C14 segment 24 via a Ferrier-type rearrangement in several steps. 

Optimized rearrangement conditions in presence of excess silylketene acetal. Rearrangement in the presence of dihydropyrane, re-addition of PhSeOH. 

Several ways to suppress the 2-oxonium-[3,3]-rearrangements might be envisioned. Apart from the introduction of a bulky substituent R at the aldehyde (Scheme 23) a similar steric repulsion between R and R might also be observed upon introduction of a bulky auxiliary at R. A proof-of-principle for this concept was observed upon by using of a trimethylsilyl group as substituent R in the alkyne moiety (Scheme 25, R = TMS). This improvement provided an efficient access to polysubstituted dihydropyrans via a silyl alkyne-Prins cyclization. Ab initio theoretical calculations support the proposed mechanism. Moreover, the use of enantiomerically enriched secondary homopropargylic alcohols yielded the corresponding oxa-cycles with similar enantiomeric purity [38]. 

An additional example of an oxonium ion generated via the acid catalyzed rearrangement has been used to prepare a dihydropyran <06TL6149>. The oxonium ion 54 generated by the reaction of an epoxide with ZrCl4 can be trapped by a nucleophile such as butynol to prepare dihydropyran 55. A variety of mono- and disubstituted epoxides have been used in this reaction. 

The application of RCM to dihydropyran synthesis includes a route to 2,2-disubstituted derivatives from a-hydroxycarboxylic acids. In a one-pot reaction, the hydroxy esters undergo sequential O-allylation, a Wittig rearrangement and a second O-allylation to form allyl homoallyl ethers 8. A single RCM then yields the 3,6-dihydro-2//-pyran 9. The process is readily adapted not only to variably substituted dihydropyrans but also to 2-dihydrofuranyl and 2-tetrahydrooxepinyl derivatives and to spirocycles e.g. 10 through a double RCM (Scheme 4) <00JCS(P1)2916>. 

Tetrahydropyran epoxides 12, the synthesis of which involves a RCM, undergo a base-induced rearrangement to 3,4-dihydro-2//-pyran-4-ols 13. These compounds are converted stereospecifically to 3,6-dihydropyrans 14 on treatment with allyltrimethylsilane (Scheme 6) <00EJO3145>. 

Bicyclic acylcyclobutanes underwent rearrangement at 210 °C to give bicyclic dihydropyrans 2.120 At 150-180 °C a competing Cope rearrangement of the corresponding enol to give 1 predominated.120... 

The rearrangement of dihydropyran sulfoxide 290 to 2//-thiopyran derivative 291302 was mentioned in Section IV,E. An unusual dehydrochlorination of 3-thiabicyclo[3.1.0]hexane S,5-dioxides 364 aifording 2H-... 

The reactions of vinyl ethers with sulfonyl azides have been described by several authors.260-273-275 From dihydropyran the arylsulfonimines of 5-valerolactone (87) are obtained. These compounds rearrange at ca. 180° into N-arylsulfonyl-2-piperidones (88) (Chapman rearrangement).276... 

By analogy with the conversion of tetrahydrofurfuryl alcohol into dihydropyran, the action of heat on 2,3-dihydro-2-hydroxymethylbenzofuran might be considered a potential source of chrom-2-ene. Whilst the reaction is indeed successful, 2-methylbenzofuran is also produced and separation of the two compounds is difficult (54MI22400). It thus appears that there is competition between proton loss before and after a Wagner-Meerwein rearrangement. 

Electron-rich conjugated dienes add across the carbon-oxygen double bond of ketene to give substituted dihydropyrans (424) which rearrange to pyran-4-ones (Scheme 143) (82S500). 

The [4 + 2] cycloaddition of a-phenylselenopropenoyl trimethylsilane (75) with 2,3-dimethylbuta-1,3-diene is unusual in that a significant portion of product mixture consists of the hetero-Diels-Alder dihydropyran adduct 76. The phenylselenenyl substituent appears to be responsible for this unusual pattern of reactivity, since propenoyl trimethylsilane gives only the expected regioisomer (77, X = H) (Scheme 116)14. a-Selenenyl substituted a,/l-unsaturated acyl silanes such as 75 were used to prepare a series of substituted dienes in excellent yields through the addition of a-sulphinyl carbanions, Brook rearrangement and expulsion of sulphinate, in a reaction pathway recognisably more typical of acyl silanes (Scheme 117). 

As early as 1997, Hiemstra and Speckamp postulated the participation of an oxonia-Cope rearrangement as a crucial step during the cyclization of vinyl silane 146 (Scheme 13.50) [75]. Both ( )- and (Z)-vinylsilanes, (E)-146 and (Z)-146 respectively, were used in this study. The cyclization proceeded in both cases in good to excellent yields, furnishing the 2,6-disubstituted dihydropyrans 147. Surprisingly, the cyclization of (E)-vinylsilanes ( )-146 gave anti-2,6-dihydropyran anti-147 as the major stereoisomer, whilst in the case of (Z)-vinylsilane (Z)-146, the syn-dihydropyran syn-147 was formed as the major product. 

Bis(diethylamino) silol complexes, preparation, 3, 435 Bis-dihydropyran, via ring-rearrangement reactions, 11, 260 1,3-Bis(dimethylchlorosilyl)cyclodisilazane, preparation,... 

Enyne 190 undergoes platinum(n)-catalyzed ring closures to afford the cyclopropyl-fused 3,4-dihydropyran 191. The reaction is thought to proceed via formation and rearrangement of the intermediate cyclobutyl cation 192 (Scheme 59) <2000JA6785, 2001JA11863>. 

Zeise s dimer can catalyze a rearrangement of the fused cyclopropane 217 to afford the 3,4-dihydropyran 218 in moderate yield (Equation 101) <2003T2765>. 

The reaction of ketene with a,(1-unsaturated carbonyl compounds in the presence of a cationic palladium(ll) complex leads to the formation of 4-vinyloxetan-2-one intermediates 863, which rearrange under the reaction conditions to give 3,6-dihydropyran-2-ones 864. ot,(3-Unsaturated aldehydes provide higher yields of the desired 3,6-dihydropyran-2-ones than their corresponding ketones (Scheme 239, Table 37) <2000CC73, 2002T5215>. 

An hDA reaction of the thermally generated (trialkylsilyl)vinylketene 888 with diethyl ketomalonate furnishes the 5,6-dihydropyran-2-one 889 in excellent yield. Protodesilylation of the cycloadduct 889 is achieved in quantitative yield upon its exposure to methanesulfonic acid (Scheme 244). A photochemical Wolff rearrangement of the silyl diazo compound 890 can also be used to generate an intermediate diene for reaction with diethyl ketomalonate to afford the 5,6-dihydropyran-2-ones 891 (Equation 358) <19990L641>. 

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