Cyclizations suprafacial

Thermal and photochemical cycloaddition reactions always take place with opposite stereochemistry. As with electrocyclic reactions, we can categorize cycloadditions according to the total number of electron pairs (double bonds) involved in the rearrangement. Thus, a thermal Diels-Alder [4 + 2] reaction between a diene and a dienophile involves an odd number (three) of electron pairs and takes place by a suprafacial pathway. A thermal [2 + 2] reaction between two alkenes involves an even number (two) of electron pairs and must take place by an antarafacial pathway. For photochemical cyclizations, these selectivities are reversed. The general rules are given in Table 30.2. 

This type of ring-closure reaction is exemplified in Scheme 9 by the thermal isomerization of 100 to 101 <1995SL622, 1998T927, 2004GC125>, which involves a suprafacial [l,5]-hydrogen shift of one of the methylene protons adjacent to the amino group of 100 followed by cyclization. 

The photocyclization of enamides has been the subject of detailed study and provides a valuable approach to the synthesis of alkaloids. A comprehensive review has been published.31 A variety of reaction types has been reported. The N-benzoylenamine 33, for example, is converted on irradiation to the trans-lactam 34 by a process involving conrotatory photocyclization followed by a thermally allowed [l,5]-suprafacial hydrogen migration.32 The influence of substituents on this transformation has been studied.33 The enacylamine 35 undergoes an analogous cyclization to give a mixture of cis- and trans-lactams 36, the ratio of which is solvent... 

Electrocyclization of 1,4-dienes is an efficient process when a heteroatom with a lone pair of electrons is placed in the 3-position, as in 77 (Scheme 20)38. Photoexcitation of these systems generally results in efficient formation of a C—C bond via 6e conrotatory cyclization to afford the ylide 78. These reactive intermediates can undergo a variety of processes, including H-transfer (via a suprafacial 1,4-H transfer) to 79 or oxidation to 80. In a spectacular example of reaction, and the potential it holds for complex molecule synthesis, Dittami and coworkers found that the zwitterion formed by photolysis of divinyl ether 81 could be efficiently trapped in an intramolecular [3 + 2] cycloaddition by the... 

Thermal addition of hydroxylamines to non-activated C=C bonds has been observed only during cyclization processes The reaction proceeds through a thermal retro-Cope mechanism as evidenced by its suprafacial stereospecihcity (equation 37). ... 

In the reaction of (Z)-2-bromo-2-butenoic acid the cyclic product (495) has the trans configuration. Since the cyclization reaction proceeds with inversion, the adduct formation is suprafacial. This is further confirmed by the reaction between 2-bromocyclohex-2-enone and mercaptopyridines where it has been shown that the dihydrothiazole and the cyclohexane rings are c/s-fused. 

Whether the reaction is supra- or antarafacial ought to be reflected in the relative stereochemistry of the cyclized products—and indeed it is. This reaction gives solely the diastereoisomer on the left, with the methyl groups syn—clear proof that the reaction is suprafacial. This is a difficult result to explain without the enlightenment provided by the Woodward-Hoffmann rules ... 

Disrotatory and conrotatory rotation The concerted rotation around two bonds in the same direction, either clockwise or counterclockwise, is described as conrotatory. In the electrocyclic ring opening, the terminal p-orbitals rotate (or twist, roughly 90°) in the same direction known as conrotation (comparable to antarafacial) to form a new ct-bond. In disrotatory cyclization (comparable to suprafacial) the terminal p-orbitals rotate in opposite directions. These two modes of the electrocyclic reaction are shown in Fig. 8.37. 

Further biosynthetic studies by Cane et have shown that the conversion of farnesyl pyrophosphate (15) into nerolidyl pyrophosphate (16) proceeds by a net syn (suprafacial) process and that the subsequent cyclization to cyclonerodiol (17) occurs in a trans manner (Scheme 4). This careful piece of work was achieved by incorporation studies with doubly labelled nerolidol and mevalonate precursors and then by ascertaining the chirality of the acetate derived by Kuhn-Roth oxidation through enzymatic conversion (malate synthase/fumarase incubation) into labelled malate. In a subsequent series of experiments with labelled precursors, Cane et have confirmed that (i) only the C-7 hydroxy-group in cyclonerodiol is derived from water whereas the C-3 hydroxy-group is derived... 

When classifying cyclizations, the subscripts s and a are used to designate suprafacial and antarafacial, respectively. Thus, a more complete... 

Photochemical cyclization of l-(lV-methylanilino)cycloalkenes gives primarily trans-fused hexahydrocarbazole derivatives 170 (68JA5329). This cyclization may involve a conrotatory electrocyclization of divinylamines, followed by a suprafacial [l,4]-sigmatropic hydrogen shift (70CC531). The intermediates in the initial cyclization are believed to be cyclic azomethine ylide 1,3-dipoles 169, but no direct observation of the participation of such dipoles was made. All attempts to capture dipoles 169 by cycloaddition with maleic anhydride or furan were unsuccessful (71JA2918). 

Two elements of the cyclization have yet to be addressed the isomerization of geranyl pyrophosphate to linalyl pyrophosphate (or the equivalent ion-pair) and the construction of bicyclic skeleta. Studies on the biosynthesis of linalool (61), and on the analogous nerolidyl system in the sesquiterpene series (52), have shown this allylic transposition to occur by a net suprafacial process, as expected. On the other hand, the chemical conversion of acyclic or monocyclic precursors to bicyclic monoterpenes, under relevant cationic cyclization conditions, has been rarely observed (47,62-65) and, thermodynamic considerations notwithstanding (66), bicyclizations remain poorly modeled. 

As discussed in Chapter 12, electrocyclic reactions may proceed in a conrotatory or disrotatory fashion, that is, the n system cyclizes in an antarafacial or suprafacial manner, respectively. Since there is only a single component, it should be counted according to the general component analysis for a thermally allowed reaction, that is, Ti rn = conrotatory and = disrotatory. Thus, the cyclization of butadienes... 

The mechanistic details of this reaction have been examined by several workers. Absorption of a photon produces the enamine excited singlet state EA, which undergoes inter system crossing to the excited triplet state EA. Cyclization leads to an excited zwitterion ZW, which relaxes to the zwitterionic ground state (Scheme 8) . A suprafacial hydride shift produces the observed product. The presence of the zwitterionic intermediate has been detected by laser flash photolysis . In studies on the related sulfide ring closure, the zwitterion was trapped by a dipolarophile ... 

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