421
δ-functionalized acids with various commonly used heteroatoms. Nevertheless,
there are several restrictions and challenges to meet in the near future. These not
only include development of alternative more attractive and environment-friendly
catalytic procedures, but also various other factors need to be addressed. For
example, as discussed in this chapter, majority of the catalytic hetero-functionalization approaches involve carboxylic acid equivalents including amides/esters/
azoles; however, the use of a free carboxylic acid group is rather limited to mostly
lactonization (intramolecular C–O bond formation). Furthermore, the synthesis
of optically active stereogenic centers by using these hetero-functionalization
approaches is underdeveloped and needs to be established. Applications of
organo- and photocatalysts in the hetero-functionalization of carboxylic acids
also remain in their infancy [125–129]. Although these issues remained to be
solved, we sincerely believe that the various techniques thus far available for the
direct hetero- functionalization of C(sp
3
)–H bonds of substrates bearing carboxyequivalent groups will be applied to broad sectors of academia and industry in the
near future.
Acknowledgments The authors thank CSIR (CSMCRI project no. MLP 0028) and DST (Grant
no. DST/INSPIRE/04/2015/002248) for financial support. CSIR-CSMCRI Communication no.
10/2020.
References
1. Hansch C, Sammes PG, Taylor JB (eds) (1990) Comprehensive medicinal chemistry: the
rational design, mechanistic study & therapeutic application of chemical compounds.
Pergamon Press, Oxford, pp 12–27
2. Harada N, Watanabe M, Kuwahara S, Sugio A, Kasai Y, Ichikawa A (2000) 2-Methoxy-2(1-naphthyl)propionic acid, a powerful chiral auxiliary for enantioresolution of alcohols
and determination of their absolute configurations by the 1H NMR anisotropy method.
Tetrahedron Asymmetry 11:1249–1253
3. Fraústo da Silva JR, RJP W (eds) (2001) The biological chemistry of the elements. Oxford
University Press, New York
4. Kasai Y, Watanabe M, Harada N (2003) Convenient method for determining the absolute
configuration of chiral alcohols with racemic 1H NMR anisotropy reagent, MαNP acid: Use
of HPLC‐CD detector. Chirality 15:295–299
5. Seco JM, Quiñoá E, Riguera R (2004) The assignment of absolute configuration by
NMR. Chem Rev 104:17–118
6. Carballeira NM, Miranda C, Orellano EA, González FA (2005) Synthesis of a novel series of
2-methylsulfanyl fatty acids and their toxicity on the human K-562 and U-937 leukemia cell
lines. Lipids 40:1063–1067
7. Mellah M, Voituriez A, Schulz E (2007) Chiral sulfur ligands for asymmetric catalysis. Chem
Rev 107:5133–5209
8. Deaton DN, Gao EN, Graham KP, Gross JW, Miller AB, Strelow JM (2008) Thiol-based
angiotensin-converting enzyme 2 inhibitors: P1 modifications for the exploration of the S1
subsite. Bioorg Med Chem Lett 18:732–737
9. Maji B, Mayr H (2012) Structures and reactivities of O‐methylated breslow intermediates.
Angew Chem Int Ed 51:10408–10412
C(sp
3
)–H Bond Hetero-functionalization of Aliphatic Carboxylic Acid Equivalents…
δ-functionalized acids with various commonly used heteroatoms. Nevertheless,
there are several restrictions and challenges to meet in the near future. These not
only include development of alternative more attractive and environment-friendly
catalytic procedures, but also various other factors need to be addressed. For
example, as discussed in this chapter, majority of the catalytic hetero-functionalization approaches involve carboxylic acid equivalents including amides/esters/
azoles; however, the use of a free carboxylic acid group is rather limited to mostly
lactonization (intramolecular C–O bond formation). Furthermore, the synthesis
of optically active stereogenic centers by using these hetero-functionalization
approaches is underdeveloped and needs to be established. Applications of
organo- and photocatalysts in the hetero-functionalization of carboxylic acids
also remain in their infancy [125–129]. Although these issues remained to be
solved, we sincerely believe that the various techniques thus far available for the
direct hetero- functionalization of C(sp
3
)–H bonds of substrates bearing carboxyequivalent groups will be applied to broad sectors of academia and industry in the
near future.
Acknowledgments The authors thank CSIR (CSMCRI project no. MLP 0028) and DST (Grant
no. DST/INSPIRE/04/2015/002248) for financial support. CSIR-CSMCRI Communication no.
10/2020.
References
1. Hansch C, Sammes PG, Taylor JB (eds) (1990) Comprehensive medicinal chemistry: the
rational design, mechanistic study & therapeutic application of chemical compounds.
Pergamon Press, Oxford, pp 12–27
2. Harada N, Watanabe M, Kuwahara S, Sugio A, Kasai Y, Ichikawa A (2000) 2-Methoxy-2(1-naphthyl)propionic acid, a powerful chiral auxiliary for enantioresolution of alcohols
and determination of their absolute configurations by the 1H NMR anisotropy method.
Tetrahedron Asymmetry 11:1249–1253
3. Fraústo da Silva JR, RJP W (eds) (2001) The biological chemistry of the elements. Oxford
University Press, New York
4. Kasai Y, Watanabe M, Harada N (2003) Convenient method for determining the absolute
configuration of chiral alcohols with racemic 1H NMR anisotropy reagent, MαNP acid: Use
of HPLC‐CD detector. Chirality 15:295–299
5. Seco JM, Quiñoá E, Riguera R (2004) The assignment of absolute configuration by
NMR. Chem Rev 104:17–118
6. Carballeira NM, Miranda C, Orellano EA, González FA (2005) Synthesis of a novel series of
2-methylsulfanyl fatty acids and their toxicity on the human K-562 and U-937 leukemia cell
lines. Lipids 40:1063–1067
7. Mellah M, Voituriez A, Schulz E (2007) Chiral sulfur ligands for asymmetric catalysis. Chem
Rev 107:5133–5209
8. Deaton DN, Gao EN, Graham KP, Gross JW, Miller AB, Strelow JM (2008) Thiol-based
angiotensin-converting enzyme 2 inhibitors: P1 modifications for the exploration of the S1
subsite. Bioorg Med Chem Lett 18:732–737
9. Maji B, Mayr H (2012) Structures and reactivities of O‐methylated breslow intermediates.
Angew Chem Int Ed 51:10408–10412
C(sp
3
)–H Bond Hetero-functionalization of Aliphatic Carboxylic Acid Equivalents…