Retrosynthetic analysis carbon skeleton

Retrosynthetic analysis strategies for designing a synthetic project, including construction of the carbon skeleton and control of stereochemistry and enantioselectivity... 

Our first approach to 1 is based on a retrosynthetic analysis depicted in Fig (8). The crucial step to construct the cw-fused bicyclic ring skeleton of 1 is the intramolecular allylic amination of a cw-allylic carbonate 25. The paUadium-catalyzed allylation takes place with retention of the configuration [76] and requires the c/s-isomer 25 for the ring closure. Compound 25 may be derived from keto acid 24 through a sequence of reactions including esterification, O-methoxycarbonylation, removal of the Boc and benzylidene groups, dehydrative cyclization, reductive alkylation and ureido formation. The last five transformations are to be conducted in a successive manner, i.e., without isolation of the intermediates. The 4-carboxybutyl chain of 1 may be installed by the reaction of O-trimethylsilyl (TMS) cyanohydrin 23 with a di-Grignard... 

On the occasion of complex natural products synthesis, choice of the starting material(s) becomes a key for success of the aim in many cases. Along with well-designed retrosynthetic analysis and sophisticated synthetic schemes, availability of the starting materials, desirably in enantiomerically pure or enriched form, is an indispensable element. During these fifteen years we have extensively explored the stereoselective introduction of synthetically versatile carbon functionalities on the carbohydrate skeletons in hope of novel access to a variety of enantiomerically pure building blocks (so-called chirons ) [1-3]. For instance, we reported in 1985 that the thermal Claisen... 

Helquist and co-workers " targeted a late-stage macrolactamization of 1227 to assemble the entire carbon skeleton of madumycin 11226. Further retrosynthetic analysis focused on the final assembly of 1227, involving a 5-hydroxy-2-alkenoic acid fragment 1228, o-alanine, and an oxazole-pentadiene unit 1229 (Scheme 1.312). These authors had adapted their oxazol-2-ylzinc Reformatsky-... 

This chiral auxiliary has been applied to the enantioselective synthesis of a-alkyl carboxylic acids such as (5 )-2-methyl-4-pentenoic acid. A retrosynthetic analysis of the carbon skeleton of 2-methyl-4-pentenoic acid suggests preparation by alkylation of the enolate of a propanoyl group with an allyl halide. 

Use retrosynthetic analysis to propose effective single-step and multistep syntheses of compounds using alcohols as intermediates (especially those using Grignard and organolithium reagents to assemble the carbon skeletons). 

In Section 7.15B you learned about retrosynthetic analysis and how this kind of thinking could be applied to the construction of carbon skeletons of alkanes and cycloalkanes. 

Retrosynthetic analysis of the target coumarin skeleton provides two major synthetic routes (Figure 10.1). Route A requires an aromatic o-hydroxy carbonyl compound and a two-carbon fragment observed in Knoevenagel and Perkin reactions reflecting the [4h-2] approach for the construction of six-membered heterocycles. Route B represents the reaction between phenols and three carbon fragments associated with the Pechmann cyclization. In recent years, newer synthetic methodologies have also been applied to the synthesis of a variety of coumarins that have avoided the use of concentrated sulfuric acid. The present chapter reviews various... 

As shown in the following retrosynthetic analysis, this molecule can be constructed from the carbon skeletons of ethyl acetoacetate and methyl vinyl ketone. 

Here it is important to note the principle difference between the retrosynthetic steps in Schemes 1.3 and 1.4. In the first one we anticipate interconversion of the functional group (FGI), in the second one the disconnection of the C-C bond (DIS). They reflect the difference between two basic types of reactions in synthetic organic chemistry the transformation of one functional group and formation of a new C-C bond. By far more synthetically important are C-C bond-forming reactions, which enhance the complexity of the carbon skeleton. A rather sharp difference between these two types of reactions in synthetic organic chemistry is reflected in retrosynthetic analysis. Disconnection of the C-C bond in TM la is presented in some detail (Scheme 1.5). 

The first successful synthesis of longifolene was described in detail by Corey and coworkers in 1964. Scheme 11.15 presents a retrosynthetic analysis corresponding to this route. A key disconnection is made on going from 1 -> II. This simplifies the tricyclic skeleton to a bicyclic one. For this disconnection to correspond to a reasonable synthetic step, the functionality must engender mutual reactivity between carbon atoms 7 and 10. This is achieved in diketone II since the enolate of the C-11 carbonyl, which is nucleophilic at C-10 can undergo Michael addition to the C-7 carbon. Step II III is retrosynthetically attractive since it gives a... 

A retrosynthetic analysis corresponding to the synthesis in Scheme 11.19 is shown in Scheme 11.18. The striking feature of this synthesis is the structural simplicity of the key intermediate IV. A synthesis according to this scheme would generate the tricyclic skeleton in a single step from a monocyclic intermediate. The disconnection III IV corresponds to a cationic cyclization of the highly symmetric cationic intermediate IVa. Thus no issues of stereochemistry arise until the carbon... 

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