Retrosynthetic analysis with

Retrosynthetic analysis with acetylide anions is illustrated in Sample Problems 11.7 and 11.8. 

Scheme 15.4 Retrosynthetic analysis with the r2.31-Meisenheimer rearrangement. Scheme 15.5 Synthesis of amine IV-oxides from tertiary amines.

Scheme 15.31 Retrosynthetic analysis with the r2.31-Stevens rearrangement.

The synthetic implications of this chapter are discussed via retrosynthetic analysis with three problems. The targets are ether 163, nitrile 164, and ether 165, with the designated starting material shown in each case. Ether 163 must be made from 1-pentene, and it is clear that analyzing both molecules leads to the conclusion that no new C-C bonds must be made. All five carbon atoms of 1-pentene are found in 163. It is also clear that a C-0 bond must be made at C2 of 1-pentene. What is the source of OMe Either an alcohol must be made and then OH must be converted to OMe, or OMe must be incorporated directly. In either case, methanol is the source of OMe. 

On first sight, it is diflftcult to imagine rc/ro-Mannich disconnection as the key step in the retrosynthesis of TM 4.13. Starting the retrosynthetic analysis with the disconnection of the C=C bond in cyclic enone we arrive at a 1,5-dicarbonyl pattern in TM 4.13a (Scheme 4.41). Now two possible refro-Michael disconnections. 

We start the retrosynthetic analysis with the following observations ... 

To recognize the different levels of representation of biochemical reactions To understand metabolic reaction networks To know the principles of retrosynthetic analysis To understand the disconnection approach To become familiar with synthesis design systems... 

The Japanese program system AlPHOS is developed by Funatsu s group at Toyo-hashi Institute of Technology [40]. AlPHOS is an interactive system which performs the retrosynthetic analysis in a stepwise manner, determining at each step the synthesis precursors from the molecules of the preceding step. AlPHOS tries to combine the merits of a knowledge-based approach with those of a logic-centered approach. 

The retrosynthetic analysis of a target compound is a systematic approach in developing a synthesis plan starting with the target structure and working backward to available starting materials. 

Estrone (54, Chart 6) contains a full retron for the o-quinonemethide-Diels-Alder transform which can be directly applied to give 55. This situation, in which the Diels-Alder transform is used early in the retrosynthetic analysis, contrasts with the case of ibogamine (above), or, for example, gibberellic acid (section 6.4), and a Diels-Alder pathway is relatively easy to find and to evaluate. As indicated in Chart 6, retrosynthetic conversion of estrone to 55 produces an intermediate which is subject to further rapid simplification. This general synthetic approach has successfully been applied to estrone and various analogs. ... 

Antithetic Analysis. (Synonymous with Retrosynthetic Analysis) A problem-solving technique for transforming the structure of a synthetic target molecule to a sequence of progressively simpler structures along a pathway which ultimately leads to simple or commercially available starting materials for a chemical synthesis. 

The co-occurring marine allomones 2- and 9-isocyanopupukeanane have been synthesized from a common intermediate. This condition along with topologically based strategic disconnection had a major impact on the retrosynthetic analysis. 

Despite the structural relationship between ginkgolide B and bilobalide, retrosynthetic analysis of the latter produced a totally different collection of sequences. A successful synthesis of bilobalide was implemented using a plan which depended on stereochemical and FG-based strategies. A process for enantioselective synthesis was based on an initial enantioselective Diels-Alder step in combination with a novel annulation method. 

Venustatriol, a marine-derived antiviral agent, as with many polyether structures, is a straightforward problem for retrosynthetic analysis. The major issues, clearance of stereocenters and topologically strategic disconnection, were readily resolved to generate the pathway of synthesis described below. 

With these words, E. J. Corey defines for us the concept of retro-synthetic analysis for which he received the Nobel Prize in chemistry in 1990. Nowadays, it has become routine to think about a target molecule in terms of its retrosynthetic analysis. Furthermore, it is hard to imagine how chemists developed synthetic strategies prior to the formulation of these concepts in the 1960s, without thinking, at least subconsciously, in these terms about complex organic structures. 

Scheme 1 outlines the retrosynthetic analysis of the Woodward-Eschenmoser A-B variant of the vitamin B12 (1) synthesis. The analysis begins with cobyric acid (4) because it was demonstrated in 1960 that this compound can be smoothly converted to vitamin B12.5 In two exploratory corrin model syntheses to both approaches to the synthesis of cobyric acid,6 the ability of secocorrinoid structures (e. g. 5) to bind metal atoms was found to be central to the success of the macrocyclization reaction to give intact corrinoid structures. In the Woodward-Eschenmoser synthesis of cobyric acid, the cobalt atom situated in the center of intermediate 5 organizes the structure of the secocorrin, and promotes the cyclization... 

A retrosynthetic analysis of fragment 152 can be completed through cleavage of the C16-C17 bond in enone 155, the projected precursor of epoxide 152. This retrosynthetic maneuver furnishes intermediates 156 and 157 as potential building blocks. In the forward sense, acylation of a vinyl metal species derived from 156 with Weinreb amide 157 could accomplish the construction of enone 155. Iodide 153, on the other hand, can be traced retrosynthetically to the commercially available, optically active building block methyl (S)-(+)-3-hydroxy-2-methyIpropionate (154). 

We now tum our attention to the C21-C28 fragment 158. Our retrosynthetic analysis of 158 (see Scheme 42) identifies an expedient synthetic pathway that features the union of two chiral pool derived building blocks (161+162) through an Evans asymmetric aldol reaction. Aldehyde 162, the projected electrophile for the aldol reaction, can be crafted in enantiomerically pure form from commercially available 1,3,4,6-di-O-benzylidene-D-mannitol (183) (see Scheme 45). As anticipated, the two free hydroxyls in the latter substance are methylated smoothly upon exposure to several equivalents each of sodium hydride and methyl iodide. Tetraol 184 can then be revealed after hydrogenolysis of both benzylidene acetals. With four free hydroxyl groups, compound 184 could conceivably present differentiation problems nevertheless, it is possible to selectively protect the two primary hydroxyl groups in 184 in... 

Proceeding with the retrosynthetic analysis, it is now timely to address the issue of the rather sensitive oxetane ring. Disconnection of the C5-0 bond as indicated in structure 5 and engagement of... 

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