Propargylic-allylic anion

A very interesting and powerful new cyclization method employing intramolecular attack of a propargylic-allylic anion at a propargylic aldehyde is the Nozaki cyclization [Eq. (10)] even the heavily strained nine-membered ring 37 can be obtained by this procedure [18]. 

The 1,3-dipoles consist of elements from main groups IV, V, and VI. The parent 1,3-dipoles consist of elements from the second row and the central atom of the dipole is limited to N or O [10]. Thus, a limited number of structures can be formed by permutations of N, C, and O. If higher row elements are excluded twelve allyl anion type and six propargyl/allenyl anion type 1,3-dipoles can be obtained. However, metal-catalyzed asymmetric 1,3-dipolar cycloaddition reactions have only been explored for the five types of dipole shown in Scheme 6.2. 

All 1,3-dipoles contain an allyl anion type n system, i.e., four electrons delocalized over three parallel atomic n orbitals, but, in addition, 1,3-dipoles of the propargyl-allenyl type contain an additional n bond in the plane perpendicular to the allyl anion MO (Fig. 1). 

One potential problem in the reactions of stabilized allylic or propargylic carb-anions is the dimerization of the starting material if the carbanions are not formed stoichiometrically. Alkenes substituted with electron-withdrawing groups are good Michael acceptors, to which nucleophiles will undergo conjugate addition. For instance, the Baylis-Hillman reaction of allyl cyanide with benzaldehyde requires careful optimization of the reaction conditions to avoid dimerization of the nitrile (Scheme 5.12). This problem is related to a common side reaction of Michael additions reaction of the product with the Michael acceptor (Scheme 10.21). 

According to Huisgen (1963), a 1,3-dipole is a compound isoelectronic with either propargyl anion, [CH=CH—CH2], or allyl anion, [CH2=CH—CH2] , being linear and bent species, respectively. On the other hand, the dipolarophile is an unsaturated compound. Thus, the above equation can be more explicitly written ... 

A 1,3-dipole as shown in Schemes 6-5 and 6-6 corresponds to a system with three parallel atomic p-orbitals, i.e., to an allyl anion, but without net charge. It is, therefore, called an allyl-type 1,3-dipole. The system may contain, however, an additional 7i-bond in the plane perpendicular to the allyl anion type molecular oribtal, and then belongs to the propargyl - allenyl type. Normally, 1,3-dipoles of this type are linear, whereas those of the allyl type are bent. The term 1,3 relates to the reactivity in these positions, not to formal charges. A series of theoretical studies (e. g., by Hiberty and Leforestier, 1978 Yamaguchi et al., 1980 see review of Houk and Yamaguchi, 1984) clearly show, however, that some of these 1,3-dipoles have considerable biradical character (e.g., O3 53% and CH2N2 28% in ab initio calculations at the 4-3IG level). We will return to biradicals in the mechanistic discussion of Sect. 6.3. 

The kind of dipoles that feature in the 1,3-DPCAs are isoelectronic with an allyl or propargyl anion system. They have a 7u-electron system consisting of two filled and one empty orbital, and both ends of the dipole have nucleophilic as well as electrophilic properties. 1,3-Dipoles of the allyl anion type are bent as the system has four electrons in three parallel p -orbitals perpendicular to the plane of the dipole. On the other hand, the presence of a double bond orthogonal to the delocalized 7r-system in the propargyl/aUenyl anion type causes linearity to the dipole (Figure 5.9). 

Svndiesis (Crombie, J. Chem. Soc. (C), 1969, 1016). The acetylenic bromide corresponding to allyl bromide is called propargyl bromide and is reactive and readily available. We shall need to protect the ketone before we make the acetylene anion. It turns out tliat protection and decarboxylation can be done in one step. 

The difference in reactivity between the anions generated from LDA and LHMDS is difficult to rationalize, but nonetheless reproducible. The same effect has been observed with substituted allyl halides and propargyl halides. Instability of the product under the reaction conditions may account for this phenomenon. Thus, for alkylation of allylic and propargylic halides, LHMDS and KHMDS are the bases of choice. 

In Chapter 10 of Part A, the mechanistic classification of 1,3-dipolar cycloadditions as concerted cycloadditions was developed. Dipolar cycloaddition reactions are useful both for syntheses of heterocyclic compounds and for carbon-carbon bond formation. Table 6.2 lists some of the types of molecules that are capable of dipolar cycloaddition. These molecules, which are called 1,3-dipoles, have it electron systems that are isoelectronic with allyl or propargyl anions, consisting of two filled and one empty orbital. Each molecule has at least one charge-separated resonance structure with opposite charges in a 1,3-relationship, and it is this structural feature that leads to the name 1,3-dipolar cycloadditions for this class of reactions.136... 

The following two-step operation was chosen as an example of the former case. The first step involves an allylation to generate the 1,6-enyne intermediate 1, via the reaction between a metal n -allyl complex derived from 52 and propargyl anion 51, followed by the PK-type reaction to furnish the bicyclopentenone 2 (Scheme 11.13). Since these two specific reactions have opposing electronic requirements (the first prefers Lewis basic character, while the second can be facilitated by Lewis acidic catalysts), finding the right combination of catalysts was the key to success. 

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