Intramolecular Sigmatropic Rearrangements

The presence of a quaternary carbon atom is frequently encountered in sesquiterpene natural products and it often creates a synthetic challenge when two or more quaternary carbon atoms are present contiguously. The synthetic strategies for the construction of quaternary carbon centers involve sigmatropic rearrangements/ intramolecular cycloaddition/ and the reaction of tertiary carbon nucleophiles with a carbon electrophile. Recently, radical cyclization strategies turned out to be very effective for this purpose. For example, Srikrishna utilized the radical cyclization reaction to prepare tricyclo[6.2.1.0 - ]undecane system, which is present in several sesquiterpenes such as zizaenes and prelacinanes, and Chen demonstrated that a tandem radical cyclization approach is an efficient method for constructing the two quaternary carbon centers in the cedrene skeleton. ... 

The treatment of 6-methyl-3-(prop-2-ynylsulfanyl)-1,2,4-triazin-5(2f/)-one with a catal)4ic amount of Pd(PhCN)2Cl2 in HMPT afforded 2,6-dimethyl-7/f-thiazolo- [3,2-fc][l,2,4]triazin-7-one via propargyl-allenyl-[3,3] sigmatropic rearrangement, intramolecular hydrothiolation, and C=C bond isomerization (eq 195).i" ... 

Aromatic Substitution (Carey Sundberg, Chapter 11) Intramolecular Wittig Reaction Sigmatropic Rearrangements... 

The aza-Cope/Mannich reaction takes advantage of the facility with which a y,<5-unsaturated itninium ion, such as 6, participates in a [3,3] sigmatropic rearrangement to give an isomeric species which is suitably functionalized for an intramolecular and irreversible Mannich cyclization (see intermediate 7). The aza-Cope rearrangement substrate 6 is simply an unsaturated iminium ion which can be fashioned in a number of ways from a homoallylic... 

An intramolecular rearrangement of the conjugate acid of the triazene compound to form the oc-complex without an additional molecule of amine would correspond to a thermal [l,3]-sigmatropic rearrangement. However, such a mechanism can be ruled out on the grounds of the antarafacial pathway required from orbital symmetry considerations (Woodward-Hoffmann rules). 

Recently, a simple and general synthetic method for the preparation of N-alkylisothioazolidines involving [2,3]-sigmatropic rearrangement of appropriately substituted allylic sulfoxides to corresponding sulfenates, followed by intramolecular substitution of the latter, has been described (equation 28)126. 

A sigmatropic rearrangement is defined as migration, in an uncatalyzed intramolecular process, of a a bond, adjacent to one or more n systems, to a new position in a molecule, with the n systems becoming reorganized in the process. Examples... 

The thiol 48 (with R R, R = H) undergoes intramolecular cychsation in THF, in the presence of AIBN under UV irradiation, to give a 2-phosphonothiolane [36], a phosphorus and sulfur analogue of proline. More recently, an asymmetric version of the sequence, [2,3]-sigmatropic rearrangement and radical cychsation, has been carried out (see Sect. 5.1.1.) [41]. 

Kanematsu s group used a combination of an intramolecular [2+2] cycloaddition of an allenyl ether 4-202 followed by a [3+3] sigmatropic rearrangement (Scheme 4.44) [70]. The substrate for the domino reaction can be obtained in situ by treat-... 

Alcaide, Aknendros and coworkers developed a combination of a 3,3-sigmatropic rearrangement of the methanesulfonate of an a-allenic alcohol to give a 1,3-bu-tadiene which is intercepted by a dienophile present in the molecule to undergo an intramolecular Diels-Alder reaction [83]. Thus, on treatment of 4-236 with CH3S02C1, the methanesulfonate was first formed as intermediate, and at higher temperature this underwent a transposition to give 4-237 (Scheme 4.51). This then led directly to the cycloadduct 4-238 via an exo transition state. 

Majumdar and coworkers used a combination of a 3,3-sigmatropic rearrangement followed by an intramolecular [1,6]-Michael addition for the synthesis of py-rimidine-annulated heterocycfes as 4-308 from 4-307 (Scheme 4.66) [103]. 

If propargyl sulfmates 422 are thermolyzed, the same carbocycles 424 are formed via [2,3]-sigmatropic rearrangement followed by intramolecular ene reaction. 

Labelling experiments using both 15N and 2H indicate that the rearrangement is intramolecular. Reactions are also acid-catalysed and are believed to occur via the Wheland intermediates 74 and 75. The most likely interpretation is that the rearrangement occurs within the Wheland intermediate by a direct 1,3-shift rather than by consecutive 1,2-shifts, and that the process can be regarded as a typical [l,5]-sigmatropic rearrangement. 

A sigmatropic rearrangement "is said to be of order [ j] when a o bond, flanked by one or more n electron systems, migrates to a new position whose termini are i-1 and j-1 removed from the original bonded loci, in an uncatalysed intramolecular process" [23]. Thus the well known Claisen and Cope rearrangements, for example, are sigmatropic rearrangements of the order [3,3]. 

A new synthetic method of benzofuran was reported (equation 39). The [3,31-sigma-tropic rearrangement of Af-trifluoroacetyl enehydroxylamines 136 obtained in situ by acylation of oxime ethers 135 in the presence of trifluoroacetic anhydride lead to the synthesis of cyclic or acyclic dihydrobenzofurans 138. The effects of base and temperature on the reaction products were studied. A similar pathway to that of Fisher indolization was proposed. The acylimine formed by the [3,3]-sigmatropic rearrangement of the V-trifluoroacetyl enehydroxylamine 136 gave the dihydrobenzofuran 137 by an intramolecular cyclization or the benzofuran 138 after elimination. 

A new [2,3]-sigmatropic rearrangement of the lithium salt 192 of the Af-benzyl-0-allylhydroxylamines (191) affording Af-benzyl-A-allylhydroxylamines (193) in moderate yields was reported (equation 56). The absence of crossover products confirms the intramolecular character of the transformation and an envelope transition state is proposed. The rearrangement proceeds via a transition state where facial selectivity is determined by stereoelectronic effects. 

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