Patai S., Rappoport Z. 2000 The chemistry of functional groups. The chemistry of dienes and polyenes. V. 2 / 0693 738

9. Synthetic applications of dienes and polyenes, excluding cycloadditions 723

Diels–Alder reaction, followed in tandem by a Cope rearrangement (equation 53).

(a)R = D-manno-(CHOAc)4-CH2OAc

(b)R = D-manno-(CHOH)4-CH2OH

(c)R = CHO

(d)R = CH2OH

Nitrocyclohexadiene 93a reacted with 4.0 equivalents of cyclopentadiene in toluene at 110 °C for 96 h, producing the 10-glyco-1-nitrotricyclo[5.2.2.02,6]undeca-3,8-diene 96a in 70% yield. Subsequent treatment with potassium carbonate in a methanol –water (9 : 1) solution followed by oxidative cleavage of the sugar side chain with sodium metaperiodate afforded aldehyde 96c. Reduction of the aldehyde with sodium borohydride produced alcohol 96d.

Schneider and Rehfeuter68 have reported that enantiomerically pure 1,6-disubstituted- 1,5-dienes with an aldol substitution pattern can undergo stereoselective Cope rearrangements in good yield. For example, 1,5-diene 97 underwent Cope rearrangements in toluene in sealed flasks at 180 °C for 2 h to afford, after chromatography, an 89% yield of a 97 : 3 diastereomeric mixture of 98 and 99, respectively (equation 54).

The oxy-Cope and anionic oxy-Cope rearrangements have found more widespread use in stereoselective synthesis than the Cope rearrangement70,75 – 79. Anionic oxy-Cope rearrangements can often be performed at or near room temperature. The rearrangement is compatible with many functional groups, and stereogenic centers are often introduced with a high degree of predictability70.

An antibody, originally generated against a diaryl substituted cyclohexanol derivative, has been employed to catalyze the oxy-Cope rearrangement of hexadiene 100 to aldehyde 101 (equation 55)80,81. A rate enhancement of 5300-fold over the uncatalyzed reaction was achieved.

In the total synthesis of cerorubenic acid-III methyl ester (105), diene 102 was converted to enantiopure tricyclic ketone 103 through an anionic oxy-Cope rearrangement (equation 56)82. Conversion of 102 to 103 afforded the entire ABC substructure of 104 and 105, most notably the double bond occupying a bridgehead site.

9. Synthetic applications of dienes and polyenes, excluding cycloadditions 725

(56)

H3C H

(104)R = H

(105)R = Me

2-Vinylbicyclo[2.2.2]oct-5-en-2-ols 107a–c and 108a–c, bearing dialkoxy substituents at the C-3 position, underwent base catalyzed [3,3]- and [1,3]-sigmatropic rearrangements to yield a stereocontrolled route to cis-decalins and bicyclo[4.2.2]dec-7-en-4-ones (equation 57)83. Compounds 106a–c were converted to diastereomeric alcohols 107a–c

OH

(108a−c)

726 Nanette Wachter-Jurcsak and Kimberly A. Conlon

H OCH3 O

(109)

(a) R1 = H, R2 = Ph (b) R1 = CH3, R2 = Ph

CH3

(110)

(a)R1 = H, R2 = Ph

(b)R1 = CH3, R2 = Ph

and 108a–c by treatment with vinylmagnesium bromide. Alcohols 107a and 107b underwent anionic oxy-Cope rearrangements on exposure to excess KH (5 equiv.) and in the presence of 18-crown-6 ether (3 equiv.) to produce compounds 109a and 109b, respectively. When subjected to similar conditions, however, alcohol 108a and 108b underwent [1,3]-rearrangement to yield the ring enlargement products 110a and 110b, respectively.

When R1 was methoxycarbonyl (106c), however, the reaction of each of the resulting diastereomeric bicyclic dienes, 107c and 108c, afforded products 109c and 110c. Interestingly, heating 107c in a sealed tube resulted in a 72% yield of the fused-bicyclic enol (111), presumably from hydrolysis of 109c. On the other hand, heating 108c produced only the ring enlarged product 110c in 61% yield (equation 58).

In the synthesis of (š)-palominol and (š)-dolabellatrienone from farnesol, Corey and Kania84 employed a dianion accelerated oxy-Cope rearrangement to form the 11,5-trans- fused ring system of the dolabellanes. Diol 112 was treated with potassium hydride in THF to afford a 1 : 1 mixture of products with trans-11,5-fused ring systems, 113 and 114 (equation 59). Bicyclic ˛,ˇ-unsaturated methyl ketone 114 was then converted to (š)-palominol in 90% yield with methyllithium. Subsequent oxidation of (š)-palominol with PCC gave (š)-dolabellatrienone in 71% yield.

N-Glycosyl homoallylamines have been shown to undergo a stereocontrolled Lewis acid-catalyzed aza-Cope rearrangement to produce chain-extended amino sugars85. The reactions proceed in good to excellent yields with high stereoselectivity. Schiff base 115 was converted to N-galactosyl-N-homoallylamine 116 by SnCl4-induced addition of allyltrimethylsilane or allyltributylstannane (equation 60).

H

(±)-Dolabellatrienone

B. Claisen Rearrangement

The Claisen rearrangement, discovered in 1912, has proven to be a powerful tool for the stereoselective generation of C C bonds69. It is widely employed in complex multistep syntheses (see, for example, References 86–89) and has inspired many variations, including the Carroll (1940), Eschenmoser (1964), Johnson (1970), Ireland (1972) and Reformatsky-Claisen (1973) reactions69.

9. Synthetic applications of dienes and polyenes, excluding cycloadditions 731

N-Acetyl indolin-3-one 123 was converted to 3-cyanomethyl-3-(1,1-dimethylallyl) indol-2-one, 127, by a successive isomerization–Claisen rearrangement sequence (equation 63)91. N-Acetylindolin-3-one 123 was converted in two steps to a mixture of E- and Z-isomers of 124. Isomerization of both isomers of 124 to 125 was accomplished with DBU. Claisen rearrangement of 125 afforded a 13% yield of 126, which was subsequently deprotected to give 3-cyanomethyl-3-(1,1-dimethylallyl)indol-2-one, 127, in 47% yield.

O

O

CH3CH2O

ClCH2CH(OC2H5)2 H+

LDA

O O

CH(OCH3)3 HOCH2CH2OH

(119) 60%

CH2OH

(62)

1.5 mol% Hg(OAc)2 CH2 CHOCH2CH3

O O

O

(120) 65%

O

Ketyl radical anions generated from ˛-allyloxy-˛,ˇ-unsaturated ketones have been used to trigger [3,3]-sigmatropic rearrangements resulting in the formation of ˛-hydroxy- ,υ- unsaturated methyl ketones (equation 64)92. It was postulated that formation of the tin(IV) enolate and allylic radical species 129 should induce a [3,3]-Claisen rearrangement to form the tin(IV) alkoxide radical 130. This radical anion can undergo hydrogen atom abstraction to yield tin alkoxide 131 which, on quenching with water, affords alcohol 132. To test this hypothesis, a series of six dienones were treated with tin hydride and AIBN. Refluxing