Dihydropyran, Table

Hetero-Diels-Alder reactions of other a,/i-cthylenic trifluoromethyl ketones provide a good alternative access to trifluoromethyl-substitutcd dihydropyrans (Table 7).54 These cycloadditions occur with inverse electron demand with electron-rich heterodienophiles such as vinyl ethers. They are performed under mild thermal conditions or at room temperature and are chemoselective and rcgioselective, but generally not stereoselective. 

An alternative method of masking the hydroxyl group of alcohols involves acetal formation by a nonaqueous acid-catalyzed addition of alcohol to the carbon-carbon double bond of 3-oxacyclohexene (dihydropyran) (Table 8.6, item 20).The product, an acetal, will also undergo acid-catalyzed hydrolysis, regenerating the alcohol and the hydrate of 3-oxacyclohexene (dihydropyran), 2-hydroxyoxacyclohexane (the cyclic form of 5-hydroxypentanal), as shown in Scheme 8.60. 

In contrast to alkoxycarbene complexes, most aminocarbene complexes appear too electron-rich to undergo photodriven reaction with olefins. By replacing aliphatic amino groups with the substantially less basic aryl amino groups, modest yields of cyclobutanones were achieved (Table 10) [63], (Table 11) [64]. Both reacted with dihydropyran to give modest yields of cyclobutanone. Thio-carbene complexes appeared to enjoy reactivity similar to that of alkoxycar-benes (Eq. 15) [59]. 

All reactions listed in Tables 5-7 were carried out under a nitrogen atmosphere, but with the rhodium or palladium catalysts no noticeable or only minor reduction in cyclopropane yields was observed when air was present. In contrast, air clearly had a yield-diminishing effect in the CuCl P(0-/-Pr)3-catalyzed reactions, especially with cyclohexene and 3,4-dihydropyran. Cyclohexene was oxidized to 2-cyclohexen-l-one, and 3,4-dihydropyran gave 5,6-dihydro-4-pyrone and 5,6-dihydro-2-pyrone, albeit in yields below 8 % 59). 

Illustrative examples of cleavage reactions of /V-arylbenzylaminc derivatives are listed in Table 3.25. Aromatic amines can be immobilized as /V-bcnzylanilincs by reductive amination of resin-bound aldehydes or by nucleophilic substitution of resin-bound benzyl halides (Chapter 10). The attachment of the amino group of 5-aminoin-doles to 2-chlorotrityl chloride resin has been reported [486]. Anilines have also been linked to resin-bound dihydropyran as aminals [487]. 

Some heterocycles can be linked to supports as tetrahydropyranyl derivatives. Attachment of indoles, purines, or tetrazoles (Table 3.29) has been achieved by treatment of a support-bound dihydropyran with the heterocycle in the presence of catalytic amounts of pyridinium tosylate [487], camphorsulfonic acid [539], or TFA [540] in DCE at 60-80 °C for 16-24 h. Indole-derived orthoesters, such as that in Entry 7 (Table 3.29), can be prepared by heating the indole with triethyl orthoformate (160 °C, 24 h) followed by acid-catalyzed reaction of the resulting orthoester with a resin-bound diol [541,542], As illustrated by Entry 8 (Table 3.29), indoles can also be linked to the Wang resin or related supports as carbamates. Cleavage by TFA is, how-... 

A 6-endo-txig selenoetherification of ( )-5-hydroxyalkenes 225 provides /r-2,3-selenides 226, which undergo oxidative elimination upon treatment with H202 to afford 2-aryl-3,4-dihydropyrans 227 in high yield (Scheme 65, Table 4) <2002TL1735>. 

Table 4 Formation of selenides 226 and their elimination to 3,6-dihydropyrans 227 (Scheme 65)...

An intramolecular Prins-type cyclization of a-acetoxy acetals 239 is catalyzed by (7-PrO)2Ti(NTf)2 and provides a stereoselective route to 2,6- A-substituted 3,6-dihydropyrans 240 (Equation 107, Table 5) <2004BKC1625>. 

Elimination of nitrous acid from the Michael adduct 279 arising from the reaction of lr-hex-3-en-2,5-dione with (3-nitroalkanols 280 forms an allylic alcohol intermediate 281, which cyclizes with high diastereoselectively to afford 4-dihydropyran-6-ols 282 (Scheme 71, Table 8) <2004SL2618>. 

Table 8 Formation of dihydropyran-6-ols 282 from c/s-hex-3-en-2,5-dione and-nitroalkanols 280 (Scheme 71)...

A titanium(lv)-promoted coupling of ethyl glyoxylate and dihydropyran provides an oxonium ion intermediate 388 which can be trapped with nucleophiles (NuH) providing access to 2,3-disubstituted tetrahydropyrans 389 (Scheme 91, Table 20) <1999TL1083>. This methodology is incorporated into the total synthesis of the antitumor agent mucocin <2002AGE4751>. 

Lithiation of aliphatic 1-acylbenzotriazoles 833 followed by 1,4-addition onto ogfl-unsaturated ketones affords anti-3-alkyM,6-diaryl-3,4-dihydropyran-2-ones 834 via ring closure of the enolate intermediate 835 (Scheme 235, Table 34) <2002JOC3104>. 

Addition of [1-ketoesters to unsaturated A -acylthiazolidinethiones 836 is catalyzed by the Ni(ll) Tol-BINAP Lewis acid complex 837. The initial addition products 838 cyclize upon treatment with base to afford enantiopure 3,4-dihydropyran-2-ones 839 in excellent yield (Scheme 236, Table 35) <2005JA10816>. 

Table 35 Formation of addition products 838 and their cyclization to 3,4-dihydropyran-2-ones 839 (Scheme 236)...

Table 36 Formation of 3,6-dihydropyran-2-ones 860 using both Grubbs first 855 and second 856 generation catalysts (Equation 347)...

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>. 

Treatment of keto alcohols 877 with (triphenylphosphonylidene)ethanone forms the intermediate ylide 878, which cyclizes via an intramolecular Wittig reaction to afford 5,6-dihydropyran-2-ones 879 (Scheme 243, Table 38). A slight improvement in yield can be observed by using keto alcohols masked as their 1,3-acetals <1998T2161>. 

Table 38 Cyclization of keto alcohols 877 to 5,6-dihydropyran-2-ones 879 (Scheme 243)...

Functionalized enantiopure 5,6-dihydropyran-2-ones 917 are accessible from a Cu(n)- (BOX) catalyzed reaction of ketene diethylacetal 914 and a-dicarbonyl compounds 915 followed by hydrolysis of intermediate 916 with formic acid (Scheme 249, Table 42) <2000JA11543>. 

Mo(CO)6 catalyzes the cyclization of both (E)- and (Z)-enediones 930 to dihydropyran-3-ones 931 in the presence of the oxygen donor r-butyl hydroperoxide (TBHP) (Equation 365, Table 43) <2003TL835>. 

Table 43 Geometry of alkenes 930 and their oxidative cyclization to 2,6-dihydropyran-3-ones 931 (Equation 365)...

A stereospecific synthesis of dihydropyran-4-ones 937 can been achieved by a mercury(ll)-catalyzed rearrangement of l-alkynyl-2,3-epoxy alcohols 936. The configuration of the epoxide is transferred unchanged to the product (Equation 367, Table 44) <1998JOC3798>. 

The use of the zinc complex of the BINOL ligand 946 in the hDA reaction between Danishefsky s diene 947 and aldehydes proceeds in excellent yield and enantioselectivity to afford dihydropyran-4-ones 948 (Equation 370, Table 45) <2002OL4349>. An asymmetric diethyl zinc addition can occur in tandem with the cycloaddition reaction between Danishefsky s diene 947 and isophthalaldehyde using a related catalyst 949 (Equation 371) <20030L1091, 2005T9465>. 

Hydrazone anion 957 induced ring opening of the enantiopure 4-substituted oxetan-2-ones 958 followed by cycliza-tion/dehydroamination of the resulting P-ketohydrazones 959 affords dihydropyran-4-ones 960 in good to excellent yield and enantioselectivity (Scheme 256, Table 46) <20020L1823>. 

---