Starting materials strategy

Developing a suitable synthesis strategy for a target compound by searching for synthesis precursors, starting materials and synthesis reactions... 

How do chemists find a pathway to the synthesis of a new organic compound They try to find suitable starting materials and powerful reactions for the synthesis of the target compound. Thus, synthesis design and chemical reactions are deeply linked, since a chemical reaction is the instrument by which chemists synthesize their compounds synthesis design is a chemist s major strategy to find the most suitable procedure for a synthesis problem. 

This starting material A (also 224A) is an isomer of the ketone we made in fi ame 328, and is easy to make using the intramolecular strategy of that fi ame ... 

Chemical Modification. The chemistry and synthetic strategies used in the commercial synthesis of cephalosporins have been reviewed (87) and can be broadly divided into ( /) Selection of starting material penicillin precursors must be rearranged to the cephalosporin nucleus (2) cleavage of the acyl side chain of the precursor (2) synthesis of the C-7 and C-3 side-chain precursors (4) acylation of the C-7 amino function to introduce the desked acylamino side chain (5) kitroduction of the C-3 substituent and 6) protection and/or activation of functional groups that may be requked. 

Product Recovery. Comparison of the electrochemical cell to a chemical reactor shows the electrochemical cell to have two general features that impact product recovery. CeU product is usuaUy Uquid, can be aqueous, and is likely to contain electrolyte. In addition, there is a second product from the counter electrode, even if this is only a gas. Electrolyte conservation and purity are usual requirements. Because product separation from the starting material may be difficult, use of reaction to completion is desirable ceUs would be mn batch or plug flow. The water balance over the whole flow sheet needs to be considered, especiaUy for divided ceUs where membranes transport a number of moles of water per Earaday. At the inception of a proposed electroorganic process, the product recovery and refining should be included in the evaluation to determine tme viabUity. Thus early ceU work needs to be carried out with the preferred electrolyte/solvent and conversion. The economic aspects of product recovery strategies have been discussed (89). Some process flow sheets are also available (61). 

Structure-goal strategies—directed at the structure of a potential intermediate or potential starting material. Such a goal greatly narrows a retrosynthetic search and allows the application of bidirectional search techniques. 

Structure-goal Strategy. The use of a particular structure corresponding to a potentially available starting material or synthetic intermediate as a guide for retrosynthetic search. 

Numerous variations of the Paal-Knorr eondensation are known. The most popular methods use starting materials that are eonverted to 1,4-diearbonyls in situ and eyelize to yield furan produets without isolating their diearbonyl preeursors. Other more speeialized strategies have been developed for the preparation of heterosubstituted furans. 

Strategy Compare the product with the starting material, and catalog the differences. In this case, we need to add three carbons to the chain and reduce the triple bond. Since the starling material is a terminal alkyne that can be alkylated, we might first prepare the acetylide anion ol 1-pentyne, let it react with 1-bromopropane, and then reduce the product using catalytic hydrogenation. 

During our previous discussion of strategies for working synthesis problems in Section 8.9, we said that ids usually best to work a problem backward, or retrosyntheticnlly. Look at the target molecule and ask yourself, "What is an immediate precursor of this compound " Choose a likely answer and continue working backward, one step at a time, until you arrive at a simple starting material. Let s try some examples. 

Retrosynthetic (Sections 8.9, 16.11) A strategy for planning organic syntheses by working backward from the final product to the starting material. 

Several elegant synthetic strategies have been devised for biotin (1) this chapter describes one of the total syntheses developed at Hoffmann-La Roche. This insightful synthesis employs a derivative of L-cysteine, a readily available member of the chiral pool,2 as the starting material, and showcases the powerful intramolecular nitrone-olefin [3+2] cycloaddition reaction. 

The retrosynthetic analysis presented in Scheme 6 (for 1, 2, and 16-19) focuses on these symmetry elements, and leads to the design of a strategy that utilizes the readily available enantiomers of xylose and tartaric acid as starting materials and/or chiral auxiliaries to secure optically active materials.14 Thus by following the indicated disconnections in Scheme 6, the initially generated key intermediates 16-19 can be traced to epoxide 23 (16,19 =>23),... 

Although the yields of this method are not as high as with the [3 + 2]-strategy, the easy accessibility of the starting materials and the simplicity of the procedure makes it an attractive approach. 

Due to the inherent unsymmetric arene substitution pattern the benzannulation reaction creates a plane of chirality in the resulting tricarbonyl chromium complex, and - under achiral conditions - produces a racemic mixture of arene Cr(CO)3 complexes. Since the resolution of planar chiral arene chromium complexes can be rather tedious, diastereoselective benzannulation approaches towards optically pure planar chiral products appear highly attractive. This strategy requires the incorporation of chiral information into the starting materials which may be based on one of three options a stereogenic element can be introduced in the alkyne side chain, in the carbene carbon side chain or - most general and most attractive - in the heteroatom carbene side chain (Scheme 20). 

---