Methods of Non-a-Amino Acid Synthesis, 2nd Edition

xi

Preface to the First Edition

Amino carboxylic acids (or just amino acids) are, as a class of organic molecules,

among the most important and useful compounds known. The chemistry of amino

acids has been studied for well over a century. The importance of α-amino acids

[RCH(NH

2

)COOH] in mammalian biology and as synthetic intermediates is well

established and there have been many reviews, several monographs, and thousands of

individual research papers in this area. The synthesis of α-amino acids has also been

the subject of many books and reviews. In addition to α-amino acids, there are many

other amino carboxylic acids where the amino group is not on the carbon immedi-

ately adjacent to the carboxyl group (the α position) but rather is attached to another

carbon in the chain (e.g., the β, γ, δ carbon, etc.). These non-α-amino acids are also

components of biologically important molecules, are important in the pharmaceutical

industry, and are useful in materials science, particularly for polymer synthesis.

This monograph gives a representative overview of the synthesis of non-α-amino

acids beginning with the year 1962. With a few exceptions, citations prior to that

date are leading references taken from other citations. The work prior to 1962 is well

represented, however, in the synthetic approaches incorporated into this book since

the “early work” is the basis of most of those approaches. Every attempt was made to

give the most common and useful methods for the synthesis of non-α-amino acids.

This monograph will focus attention on acyclic amino acids of C

3

–C

10

and includes

aminoalkanoic carboxylic acids, aminoalkenoic acids, and aminoalkynoic acids.

The synthesis of amino carboxylic acids attached to or incorporated in rings of three

to ten carbons is also presented, including amino cycloalkanoic and amino cycloal-

kenoic acids. Although saturated heterocyclic derivatives and aryl substituted amino

acids are discussed, aromatic amino carboxylic acids and heteroaromatic amino car-

boxylic acids are not discussed, except where they are synthetic precursors to or

related to aliphatic amino carboxylic acids.

The primary goal of this book is to summarize synthetic approaches to non-α-

amino acids, particularly those amino acids that are key synthetic intermediates or

important compounds in their own right. Achiral amino carboxylic acids are dis-

cussed throughout and special attention is focused on both chiral nonracemic and

chiral racemic amino acids in chapter ve, emphasizing the diastereoselectivity and/

or enantioselectivity of each synthetic process. Having such synthetic information

collected in one place will, it is hoped, facilitate current research and stimulate new

research in this important area.

Saturated amino acids of all types are discussed, as well as unsaturated, alkyl

and aryl substituted, and amino acids that bear a heteroatom functional group. In

general, four structural types of alkenyl amino acids are considered. In the rst type,

the double bond can be conjugated to the carbonyl group and the amine moiety can

be attached directly to the double bond. Secondly, the amino group can be attached

to the saturated carbon chain. The third and fourth types focus on the double bond,

which can be in or out of conjugation with the carboxyl, and the amine group can