Cyclization rules

V. Behavior and Formation of the Carbinolamine Ether Linkage in Diterpenoid Alkaloids The Baldwin Cyclization Rules... 

Recently, Pelletier and Mody (87) reported an unusual rearrangement of ajaconine (80), via a disfavored 5-endo-trig ring closure, to the more stable oxazolidine ring-containing compound, 7a-hydroxyisoatisine (82). They called attention to apparent violations of Baldwin s cyclization rules (151)... 

The formation and behavior of five- and six-membered carbinolamine ethers in various diterpenoid alkaloids were examined to determine whether any further violation of Baldwin cyclization rules occurs in these alkaloids. In 1957, Marion and co-workers (153) reported the preparation of several six-membered ring-containing carbinolamine ethers from Q 9-diterpenoid... 

In summary, certain reactions with diterpenoid alkaloid imines proceeded by a disfavored 5-endo-trigonal process, whereas in other cases, such as the reactions with glycidol, a favored 6-endo-trigonal process was followed. The Baldwin rules should be modified to accomodate the exceptional behavior of the tertiary immonium salts. Recently, examples of similar reactions demonstrating the violation of the Baldwin cyclization rules have been reported (156-158). 

One typical radical reaction is cyclization. This cyclization has been used as an indirect proof for radical reactions and a strategic method for the construction of 5- and 6-membered cyclic compounds. The experienced rule for the cyclization is Baldwin s rule [19]. There are two cyclization modes, i.e. exo and endo moreover, there are three types of hybridization in a carbon atom, sp3 (tetrahedral tet), sp2 (trigonal trig), and sp (digonal dig). Baldwin s rule is the cyclization rule based on the experimentally obtained cyclization results. The cyclization mode and kinds of hybridization in an intramolecular radical acceptor are shown in Figure 1.15. 

The cyclization is highly stereoselective according to Beckwith s radical cyclization rules [73]. Thus, the allylic benzyl ether 41 (a 1 1 mixture of diastereoisomers) undergoes a... 

Figure 11. Octatrienes used to support electrocyclic cyclization rules.

The silyl enol ether 83 represents an exception from the 6-endo cyclization rule. The reason for this differing behavior can be seen in the stability of the tertiary radical intermediate and the bulkiness of the trisubstituted double bond. The alkyne substituted silyl enol ether 85 resulted in the formation of the isomeric olehns 86 and 87 in a 1 1 ratio. 

Electi ocyclic reactions are examples of cases where ic-electiDn bonds transform to sigma ones [32,49,55]. A prototype is the cyclization of butadiene to cyclobutene (Fig. 8, lower panel). In this four electron system, phase inversion occurs if no new nodes are fomred along the reaction coordinate. Therefore, when the ring closure is disrotatory, the system is Hiickel type, and the reaction a phase-inverting one. If, however, the motion is conrotatory, a new node is formed along the reaction coordinate just as in the HCl + H system. The reaction is now Mdbius type, and phase preserving. This result, which is in line with the Woodward-Hoffmann rules and with Zimmerman s Mdbius-Huckel model [20], was obtained without consideration of nuclear symmetry. This conclusion was previously reached by Goddard [22,39]. 

The direct connection of rings A and D at C l cannot be achieved by enamine or sul> fide couplings. This reaction has been carried out in almost quantitative yield by electrocyclic reactions of A/D Secocorrinoid metal complexes and constitutes a magnificent application of the Woodward-Hoffmann rules. First an antarafacial hydrogen shift from C-19 to C-1 is induced by light (sigmatropic 18-electron rearrangement), and second, a conrotatory thermally allowed cyclization of the mesoionic 16 rc-electron intermediate occurs. Only the A -trans-isomer is formed (A. Eschenmoser, 1974 A. Pfaltz, 1977). 

In contrast to pentadienyl anions, heptatrienyl anions have been found to cyclize readily to cycloheptadienyl anions. The transformation of heptatrienyl anion to cyclo-heptadienyl anion proceeds with a half-life of 13 min at — 13°C. The Woodward-Hoffinann rules predict that this would be a conrotatory closure. ... 

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. 

Scheme 2. Thermally allowed 8 n electron and 6 k electron electro-cyclizations (Woodward-Hoffmann rules).

Cram s open-chain model 229 Cram s rule 229, 233 Cram chelate model 229 Cram cyclic model 229 Cram-Felkin-Anh model 191,207, 236 f 246 cubane 12,318 cyanoacetic acid 636 f. cyanohydrin, protected 145, 150 f. cyclic carbonate protection 541 f., 657, 659 f., 666, 670 cyclization -,6-endo 734 -, 5-exo 733 f. 

The few exceptions to this general rule arise when the a-carbon carries a substituent that can stabilize carbonium-ion development well, such as oxygen or sulphur. For example, 1-trimethylsilyl trimethylsilyl enol ethers give products (72) derived from electrophilic attack at the /J-carbon, and the vinylsilane (1) reacts with a/3-unsaturated acid chlorides in a Nazarov cyclization (13) to give cyclopentenones such as (2) the isomeric vinylsilane (3), in which the directing effects are additive, gives the cyclopentenone (4) ... 

The addition, therefore, follows Markovnikov s rule. Primary alcohols give better results than secondary, and tertiary alcohols are very inactive. This is a convenient method for the preparation of tertiary ethers by the use of a suitable alkene such as Me2C=CH2. Alcohols add intramolecularly to alkenes to generate cyclic ethers, often bearing a hydroxyl unit as well. This addition can be promoted by a palladium catalyst, with migration of the double bond in the final product. Rhenium compounds also facilitate this cyclization reaction to form functionalized tetrahydrofurans. 

As applied to cycloaddition reactions the rule is that reactions are allowed only when all overlaps between the HOMO of one reactant and the LUMO of the other are such that a positive lobe overlaps only with another positive lobe and a negative lobe only with another negative lobe. We may recall that monoalkenes have two n molecular orbitals (p. 9) and that conjugated dienes have four (p. 36), as shown in Figure 15.1. A concerted cyclization of two monoalkenes (a 2 -f- 2 reaction) is not allowed because it would require that a positive lobe overlap with a negative lobe (Fig. 15.2). On the other hand, the Diels-Alder reaction (a 2 -f 4 reaction) is allowed, whether considered from either direction (Fig. 15.3). 

We may also look at this reaction from the opposite direction (ring closing). For this direction the rule is that those lobes of orbitals that overlap (in the HOMO) must be of the same sign. For thermal cyclization of butadienes, this requires conrotatory motion (Fig. 18.3). In the photochemical process the HOMO is the %3 orbital, so that disrotatory motion is required for lobes of the same sign to overlap. 

The rare [1,4] hydrogen transfer has been observed in radical cyclizations. With respect to [1,7] hydrogen shifts, the rules predict the thermal reaction to be antarafacial. Unlike the case of [1,3] shifts, the transition state is not too greatly strained, and such rearrangements have been reported, for example,... 

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