Dihydropyrans/2//-pyrans, formation

In the case of terminal alkynes having oxygenated functions in the linear chain (Scheme 10, route D), Martin, Padron, and coworkers found that homopropargylic alcohols reacted properly, yielding 2-substituted dihydropyrans as sole products, probably via a Prins-type cyclization. This cyclization provides a new approach toward 2-alkyM-halo-5,6-dihydro-2//-pyrans through a concomitant C-C and C-O bond formation (Scheme 21) [35]. 

Further examples of the use of the hDA reaction in dihydropyran synthesis include the formation of the fused pyrans 18 from vinylallenes 17 and aldehydes (Scheme 8) <00TL6781> and a trans-fused dihydropyran containing a phosphonate group 19 . A total synthesis of the 11-oxa steroid system is based on an intramolecular Diels-Alder reaction involving an orthoquinodimethane derived from a benzocyclobutene (Scheme 9) <00TL1767>. 

Pyranone 127 reacts with alkenes in the presence of cerium ammonium nitrate via a cyclization reaction that leads to the formation of furo[2,3-3]- and furo[3,2-f]-pyranones in moderate yields (Equation 60). This reaction can be extended to the synthesis of furoquinolinones <1999H(51)2881>. Dihydropyran 128, with either / -diketones or /3-keto esters, undergoes cycloaddition reactions promoted by ceric ammonium nitrate to generate furo[2,3-3]pyrans in good yields (Equation 61) <1996T12495>. 

By analogy with the formation of dihydropyrans from unsaturated carbonyl compounds and alkenes (see Section 2.24.2.7.l(i)), the synthesis of 4//-pyrans from the [4 + 23-cycloaddition of unsaturated carbonyl compounds and alkynes would seem to offer some potential. Such a reaction has indeed proved of value, but examples are largely restricted to the use of ynamines as the dienophile (76BSF987). 

As a result of their accessibility, dihydropyrans provide a useful source of 4//-pyrans. Indeed one of the earliest syntheses of the parent compound involved the pyrolysis of 2-acetoxy-3,4-dihydropyran (165) (62JA2452). The concomitant formation of acrolein, vinyl acetate and acetic acid indicates that a reverse Diels-Alder reaction competes with the pyrolysis. 

The stereoselective formation of cw-fused dihydropyrans and the steric requirements for the reaction of the norbornenyl examples support a concerted mechanism. However, boron trifluoride catalyzed rearrangements of mixtures of endo- and exo-compounds to bicyclic pyrans, i.e., stepwise reactions through cationic intermediates, are also possible38. 

Interestingly, the presence of a bis-homopropargylic secondary amide does not lead to insertion into the N-H (as happens with a tungsten catalyst [8c]) competing with formation of the dihydropyran as shown in Equation 1.4 [10]. This reaction extends to the insertion into a phenolic OH to form benzofurans (Equation 1.5). In this case, the presence of an amine such as n-butylamine or pyridine appears to be required [11]. It should be noted that insertion into the benzylic OH to form the pyran system does not compete. 

Despite the increasing information on the photochemistry of 2,4-dienones198 and other unsaturated ketones,199 as well as on the ring-chain valence isomerism of halogen-substituted pyran and dihydropyran systems,200-201 the data are still very scarce. The intermediate formation of pyrans valence-isomeric with unsaturated carbonyl compounds in the pyridine syntheses based on reactions of ammonia with aldehydes or ketones, advocated by various authors202-206 (cf. Section II,B,2,f), is still rather speculative. (See also Section II,B,2,e for the valence isomerism of 5-chloro-2,4-dienones with pyrylium chlorides.)... 

The HDA reaction features in a diastereoselective synthesis of c/j-2,6-disubstituted 5,6-dihydro-2//-pyrans, but this is based on the initial formation of a dihydropyran-4-one. Regio- and stereo- chemistry are controlled during the reduction to the pyranol and an ester enolate Claisen rearrangement completes the sequence <97AJC43>. 

A domino reaction involving two consecutive oxidations followed by a hetero Diels-Alder reaction led to the formation of bicyclic dihydropyran 14 in 74% yield (Scheme 9.3). In this process, developed by Koo et al. [5] using Mn(OAc)3 and Cu(OAc)2, the P-ketoester 11 having a geranyl group at the a-position is converted into the a-ketoester 12, which undergoes further oxidation to form the tertiary alcohol 13 and is followed by an intramolecular hetero Diels-Alder reaction to provide the desired bicyclic trans-fused dihydro cyclopenta[c]pyran 14. In 2012,... 

The hydroformylation of 2,3-dihydrofuran and 3,4-dihydro-2//-pyran can be accompanied by partial isomerization to the isomeric cyclic allyl ethers. In general, dihydrofurans as substrates require conditions milder than those used for dihydropyrans, which has been explained by the more planar structure of the five-membered ring that facilitates the formation of substrate-metal complexes [17]. 

The pyran ring features extensively in natural product chemistry, and methods for its formation are legion only a few further examples and modifications will be described here. 5,6-Dihydropyran-3(4i/)-ones (53) are good precursors of 3-hydroxy-4i/-pyran-4-ones which in turn are potent flavouring materials. Sato et al. ° have shown that they are readily prepared from 3-methyleneheptan-2,6-dione, according to Scheme 3. The overall yield by this circuitous route was quite good, but when a more straightforward cyclization was attempted only furans of type (52) were obtained. 

Compound 193 (Fig. 82) with molecular formula C20H28O4 6-(3-methyl-2-butenyl)-5-hydroxy-2,2-dimethyl-8-(2-methylpropanoyl)-1,4-benzo(3H)pyran. It has also been isolated by preparative thin layer chromatography. The red shift by 40 nm of the UV absorption maximum in alkaline conditions is typical for a para-acylphenol derivative (11). The H NMR spectrum shows the presence of the 2-methylpropanoyl side chain next to a dihydropyran ring and a 3-methyl 2-butenyl group. Hydrogenolysis of compound 194 (Fig. 82) (see 13.2.1.3.) leads to compound 196 (Fig. 82), which is identical to that obtained upon hydrogenation of 193. The formation of the aromatic derivatives 189, 190, 192 and 193 requires the loss of an isopentenyl side chain. Aromatization of colupulone occurs in strong acid (see 4.1.) or by catalytic... 

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