James B. Hendrickson

Total synthesis of the calycanthaceous alkaloids

Abstract The total synthesis of dl -calycanthine and dl -chimonanthine is described; following biogenetic precedent, the synthesis route involves oxidative dimerization of N-carbethoxy-oxytryptamine followed by reductive cyclization. The alkaloids are interconverted by acid-catalyzed isomerization. The structures of some synthetic byproducts are also discussed.

Triflamides: new acylating and triflating reagents

Durch Behandlung mit Trifluormethansulfonsaureanhydrid (I) erhalt man aus den mit z.B. NaH hergestellten Amid-Anionen wie (II) die Acylierungsmittel (III), die bestandig sind und mit nucleophilen Reagentien (IV) zu den Acylverbindungen (V) umgesetzt werden.

Synthetic manipulation of the triflone group : Formation from alcohols, constructions, and conversion to ketones and amines

Abstract The rearrangement of trifluoromethanesulfinates to trifluoromethanesulfones (“triflones”) was developed as a synthetic method for obtaining these compounds Their utility as reagents for the construction of carbon skeletons is explored with regard to reactions such as alkylation, conjugation addition, and cycloaddition. In addition, the conversion of triflones to more common functionality is described.

Molecular complexity: A simplified formula adapted to individual atoms

The Bertz formula for calculating molecular complexity is a sum of bond connectivities. This is converted to a simpler form based on the number of hydrogens attached to each atom. Also, the calculation of symmetry terms is derived from simple equations applied to atoms of the same equivalence class. We outline here a simple program (CPXCAL) in FORTRAN for microcomputer which yields the same values as Bertzs formulas. It is applied to a number of examples as well as to all four-, five-, and six-carbon skeletons to evaluate its validity. The formulas are well adapted for use in locating synthesis pathways with least molecular complexity in our synthesis program.

New “Gabriel” syntheses of amines☆

Abstract The Gabriel synthesis is generalized as monoalkylation of an ammonia or primary amine derivative with subsequent removal of the derivatizing group(s) from nitrogen. Two new derivatives for this purpose are introduced: phenacylsulfonamides and triflamides, with discussion of their generality and effectiveness.

Nuclear synthons: mesyltriflone as an olefin polyanion equivalent.

Mesyltriflone (CF3S02CH2S02CH3) is developed as a nuclear synthon reagent capable first of multiple constructions such as alkylations then of Ramberg-Backlund elimination to a substituted olefin. The alkylations are clean and regiospecific, often amenable to one-pot operation, and in most cases the elimination is smooth. A variety of examples is presented to establish the scope of the method, and the mechanism and stereochemistry are discussed. Nuclear Synthons. In our examination of the logic of synthesis design* we directed attention to the central importance of minimizing steps and of utilizing primarily construction reactions. A major corollary of these ideas is the prime importance of multiple constructions, allowing two or more constructions in one operation. Typical examples of the concept are illustrated in eq 1-4, in which the product directs the use of a particular small-

Catalysis and regioselectivity of quinone Diels–Alder reactions

In a series of six different cycloadditions of unsymmetrical quinones and alkyl-substituted butadienes, TiCl4 afforded considerable catalysis (–78 °C) and gave regioselectivity identical with that of the thermal reaction (200 °C) and therefore complementary to that BF3 catalysis.

An olefin polyanion equivalent: a new olefin synthesis from triflones

α-Trifyl-dimethylsulfone (CF3SO2CH2SO2CH3) is a reagent which allows successive polyalkylation of the two carbons with regiocontrol. The polyalkylated trifyl-sulfone then undergoes a Ramberg-Backlund reaction with loss of triflinate anion and extrusion of SO2 to form an olefin. In synthetic terms the net structural change is equivalent to regiospecific alkylation of an olefin polyanion, =CC=.

COGNOS: A BEILSTEIN-TYPE SYSTEM FOR ORGANIZING ORGANIC REACTIONS

We describe a logical system to organize and index organic reactions. This is implemented in the COGNOS program to search reaction databases for literature precedents. It is based on the net structural change in a reaction, rather than on substructure searching. This system rigorously provides a place for any possible reaction, generalizing and classifying all reactions into families by their changes in skeleton and functionality. These families are digitally identified, allowing databases to be indexed and grouped in numerical order so as to afford instant retrieval of matching reactions. The retrieved entries are further pruned by structural details at the reacting atoms to provide small, manageable sets most closely matching any input query.

Generation and enumeration of carbon skeletons

Two different programs were written to enumerate all possible carbon skeletons, i.e., saturated hydrocarbons. These enumerations were carried out fully to 11 carbon atoms and for limited numbers of rings to 16 carbon atoms. The results of the two programs were consistent with each other as well as with such previous enumerations as were available. A program to show graphically the stored skeletons was also prepared. The skeletons of commercially available starting materials are a minute subset of the total. Various ways of classifying the data into subsets are illustrated as are superstructure searches from seed skeletons