Synthetic goals

The azide anion, often in hydiazoic acid, adds in good yield and, when strong electron-withdrawing groups are present, shows the normal 2,3-orientation (58) (49). The intermediates, useful for further synthetic goals, can, for example, be converted to heterocychc products, eg (59). The yields for various R groups are as follows ... 

In designing conjunctive cyclopropyl reagents, we should consider some of the types of structural modifications that appear most useful for further synthetic goals. Such considerations define the nature of the substituents on the cyclopropyl ring and the type of reaction to be utilized. 

The same polymeric arenes that served as metallation catalysts in equation 119 can also be used for silylation in Barbier-type reactions (equation 131). The polymer is presumably converted to a lithium arene adduct that activates metallic lithium for metallation of the halogenated substrates, before addition of an electrophile to achieve the synthetic goal. Equations 132-135 illustrate some of the cases investigated. The products can be characterized by the usual spectroscopic methods . 

Alkoxy-VCP 163 was found to be a very competent reagent in the intermolecular [5+2] cycloaddition (Tab. 13.12). With some minor optimization of the previous reaction conditions, namely the use of 1,2-dichloroethane (DCE) as solvent at a higher concentration (0.5 M) and reaction temperature (80 °C), the reaction was found to be complete in minutes in some cases with 0.5 mol% [RhCl(CO)2]2, while still providing good to excellent yields of cycloheptenone products. Significantly, reactive functionahty, including unprotected alcohols and carboxylic acids, is tolerated in the reaction. The reaction is also readily scaled, with comparable isolated yields over a 100-fold increase in scale. The formation of products in minutes is of consequence, as such reactions allow for the more time-efficient reahzation of synthetic goals. 

The methods presented in the sections above are all suitable for the synthesis of lanthionines as amino acid derivatives. However, a very important synthetic goal remains the synthesis of lanthionine-containing peptides, for example the synthesis of lantibiotics and other peptide analogues where lanthionine has replaced cystine. In the following Sections some syntheses of lanthionine-containing peptides comprising analogues of cystine peptides, such as enkephalin, somatostatin, and oxytocin are described. 

Important naturally occurring tetrahydrofuran compounds which have attracted much attention in recent years as synthetic goals are the ionophores, some possessing considerable antibiotic activity examples include monensin (196) (79JA260), nonactin (194) (76CB2628) and lasalocid A (195) (78JA2933). 

Since the discovery of the Zr-catalyzed controlled monocarboalumination of alkynes in 1978 (1] (Eq. 4.1), its application to the development of a related Zr-catalyzed enantioselective carboalumination of alkenes as shown in Equation 4.2 has been an attractive but rather elusive synthetic goal. Although enantioselective hydroboration of 1,1-disubstituted alkenes produces related organoboron products, hydroboration of 1,1-disubstituted alkenes has exhibited very low levels (usually <10-20% ee) of enantioselectivity [7] (Eq. 4.3) (Scheme 4.5). 

Catalytic enantioselective single-stage carbometallation of alkenes had until recently been an elusive synthetic goal, even though its principle and potential feasibility were recognized. It is... 

In the related dithiatetrazocine series (Sections 6.11.3.3 and 6.11.3.4) attempts were made to synthesize the S- and iV-oxide derivatives using either otCPBA or N2O4 <1989CC1137, 1989J(P1)2495>. Such synthetic goals proved to be unsuccessful and may account for a similar lack of compounds relevant for discussion in the dithiadiazole series. 

The importance of supported metal nanoclusters and nanoparticles in catalysis and the rough analogy between supported nanoclusters and organo-metallic cluster compounds (those with metal-metal bonds) in catalysis have motivated researchers to find connections between these two classes of materials. Thus, an obvious synthetic goal has been size-selected metal nanoclusters on supports. 

It is my sincere hope that this book will provide synthetic chemists with new opportunities for achieving their synthetic goals. For those students who are reading the book in order to enhance their synthetic toolkit , I hope they will enjoy the variety of these new reactions which span from stoichiometric to catalytic, from natural product-based protocols to synthetic strategies employing organometallic complexes. 

More often such bromo- and iodoalkynes are employed with another synthetic goal in mind, namely, in the Cadiot-Chodkiewicz reaction for the formation of symmetric or asymmetric 1,3-diynes by reaction of the haloalkyne with a terminal alkyne (Figure 13.25). Additional reagents essential for the success of this reaction are one equivalent or more of an amine and a substoichiometric amount of Cul. As with the Cacchi and Stephens-Castro coupling reactions of Section 13.3.4, a Cu-acetylide is the reactive species in the Cadiot-Chodkiewicz coupling. It is formed in step 1 of the mechanism illustrated in Figure 13.25. 

Although rearrangements are usually seen as annoying side reactions, a clever chemist can use a rearrangement to accomplish a synthetic goal. Problem 11-15 shows how an alcohol substitution with rearrangement might be used in a synthesis. 

---