Intramolecular Diels-Alder reactions. A new entry into bridgehead bicyclo[3.n.1]alkenes

Shea, Kenneth J.; Wise, Sean

doi:10.1021/ja00488a052

Cited by 63 publications

(20 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The first step in this evaluation involved an investigation of the thermal behavior of a series of acyclic trienes (Table 1). 3 These homologous trienes were found to undergo type 2 IMDA reaction under conditions similar to those used for the thermolysis of 1 (400–500 °C, gas phase, atmospheric pressure, ca. 10–15 s contact time).…”

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

The Type 2 Intramolecular Diels-Alder Reaction: Synthesis and Chemistry of Bridgehead Alkenes

Bear

Sparks

Shea

2001

Angew. Chem. Int. Ed.

Self Cite

189

View full text Add to dashboard Cite

Anti‐Bredt alkenes, bicyclic molecules that contain a bridgehead double bond, were for many years regarded as chemical curiosities. The type 2 intramolecular Diels–Alder (IMDA) reaction provides a one‐step entry into this fascinating class of molecules. The reaction has made available numerous anti‐Bredt alkenes for structural and chemical studies. X‐ray crystallography has revealed the magnitude of the deformations associated with the bridgehead double bond, and rate studies of reactions of bridgehead alkenes have allowed quantification of the kinetic consequences of the torsional distortions. More recently, the type 2 intramolecular Diels–Alder reaction and the resulting anti‐Bredt alkenes have found application in organic synthesis. The constraints resulting from the connectivity in the Diels–Alder precursor creates a strong regio‐ and stereochemical bias in the cycloaddition step. The end result of this bias is the stereoselective synthesis of highly substituted six‐membered rings. The reaction also achieves a facile synthesis of seven‐ and eight‐membered rings in a single step from acyclic precursors. The utility of this reaction has been verified in recent applications of the type 2 IMDA reaction as a key step in the total synthesis of complex natural products.

show abstract

Section: Introductionmentioning

confidence: 97%

“…The first report of a type 2 IMDA cycloaddition appeared in 1978 3. The reaction was discovered serendipitously during a mechanistic study of the Cope rearrangement 4, 5.…”

Section: Introductionmentioning

confidence: 99%

The Type 2 Intramolecular Diels-Alder Reaction: Synthesis and Chemistry of Bridgehead Alkenes

Bear

Sparks

Shea

2001

Angew. Chem. Int. Ed.

Self Cite

189

View full text Add to dashboard Cite

show abstract

“…A two-step oxidative cleavage protocol was employed to effect tether cleavage: a-lithiation of the sultone with "BuLi followed by trapping with 2-methoxy-4,4,5,5tetramethyl-1,3,2-dioxaborolane generated the corresponding boronate, which was oxi- Recently, Winterfeldt and co-workers used a similar strategy as a key step in the preparation of myltaylenol63 [27]. This intramolecular variant of the Diels-Alder reaction has been most intensively studied by Shea and co-workers who have shown that it can be used in a variety of highly regio-and stereocontrolled cyclizations [5,291. Tethering the dienophile would control the facial selectivity of the cycloaddition with attack proceeding onto the sterically more hindered, but desired, a-face of the diene.…”

Section: I0 Use Of the Ternnoran Connection In Orpanic Svnthesismentioning

confidence: 99%

“…It is also noteworthy that this cyclization must proceed in a stepwise fashion since the starting dienophile has a truns geometry while the products possess a cis substitution pattern at C (4) and C (5). The requisite tnene 12 was synthesized from alcohol 13 and chlorodiisopropylsilyl enol ether 14.…”

mentioning

confidence: 99%

Use of the Temporary Connection in Organic Synthesis

Cox¹,

Ley²

1999

Templated Organic Synthesis

View full text Add to dashboard Cite

The reaction between a 4 x-(diene) and a 2 n-system (dienophile), otherwise known as the Diels-Alder reaction, is undoubtedly one of the most important reactions for the construction of six-membered rings. Since up to four adjacent stereogenic centers can be generated in a single step, this reaction has become particularly valuable in synthesis. A wide variety of systems have been investigated and in the case of polarized dieneklienophiles, excellent levels of stereo-and regiocontrol can be observed. However levels of regiocontrol, and sometimes stereocontrol, drop significantly in less polarized systems. rendering the reaction less useful.By joining the diene and dienophile together through a tether, the intramolecular variant provides an entry into polycyclic systems [4]. Significantly, the intramolecular Diels-Alder (IMDA) reaction differs from its intermolecular counterpart in that levels of stereocontrol, and especially regiocontrol, are usually appreciably higher, even for non-polarized systems. The tether linking the reacting n-systems increases steric and geometrical constraints by minimizing, for example, transannular and A'*3-interactions. This serves to reduce the number of possible low-energy T. S.s, accounting for the improvements in both regio-and stereocontrol. Two variants of the IMDA reaction may be recognized. In the first, the so-called Type I IMDA, the dienophile is joined to a terminal position of the diene, producing relatively strain-free bicyclic products. In the Type I1 IMDA [5], the dienophile is linked to an internal position of the diene. Cyclization in this case results in the formation of a more strained system containing a bridgehead double bond (Figure 10-2). 10.2 Cycloaddition Rractiori.~ 279 Ph 1 Me0 Figure 10-3 Triene 1 reacts through an a x 0 T. S. OSiPh,Me ,,, ,OSiPhzMe OSiPhzMe J -L OMe PhMe, 6 -+ 155"C, 145h -MePhzSiO&OMe 0 , , , . q ; i ? M e MePhpSiOy 7 MePh2SiO' MePhzSiO&OMe 0 , , , . q ; i ? M e MePhpSiOy 7MePh2SiO'Scheme 10-2 Intermolecular reaction of 6 and 7 is neither stereo-nor regioselective.Perhaps the greatest drawback with this tethering approach is the relatively poor yield in the formation of the triene IMDA precursor 1, although the reaction was not optimized. Fortin and co-workers have reported an improved procedure for the efficient formation of unsymmetrical di-tert-butylsilyl acetals using 'Bu,Si(CI)OTf, which is readily prepared from the corresponding chlorosilane [7]. Successive incorporation of the dienophile and diene is possible by exploiting the different reactivity of silyl tritlates and chlorides towards nucleophilic substitution (Scheme

show abstract

“…(1) 3-a (2) enormous importance in contemporary organic synthesk2 Recently we reported the first examiples of an intramolecular Diels-Alder reaction of the type illustrated by eq 2, where the dienophile is joined at the 2-position of the diene (type 2 IDA).3 This reaction is distinguished by the fact that a bridgehead double bond is formed in the cycloaddition step. Unlike type 1 cycloadditions, which usually result in formation of relatively strain-free products, the strain energy associated with the bridgehead alkene manifests itself in the reaction conditions necessary for cycloaddition.…”

mentioning

confidence: 99%

Applications of the intramolecular Diels-Alder reaction to the formation of strained molecules. Synthesis of bridgehead alkenes

Shea¹,

Wise²,

Burke³

et al. 1982

J. Am. Chem. Soc.

Self Cite

View full text Add to dashboard Cite

Intramolecular Diels-Alder reactions. A new entry into bridgehead bicyclo[3.n.1]alkenes

Cited by 63 publications

References 5 publications

The Type 2 Intramolecular Diels-Alder Reaction: Synthesis and Chemistry of Bridgehead Alkenes

The Type 2 Intramolecular Diels-Alder Reaction: Synthesis and Chemistry of Bridgehead Alkenes

Use of the Temporary Connection in Organic Synthesis

Applications of the intramolecular Diels-Alder reaction to the formation of strained molecules. Synthesis of bridgehead alkenes

Contact Info

Product

Resources

About