separately model enantioselectivity and product distribution. They found that product/Heck by-product ratio (P:H) correlates to steric properties of chiral phosphate
catalyst. The P:H ratio was found to be positively correlated with the Sterimol B 5
parameter for the substituent at C-6 position (B5 6 ) and a more subtle negative
correlation with the Sterimol L parameter for the substituent at the C-4 position
(L 4 ) of the catalyst. Further experiments showed that the phosphate catalyst can act
as a base to aid formation of by-product. Therefore, the QSSR supports the finding
that more sterically hindered phosphate slows down the formation of the by-product,
hence decreasing the kinetically competing Heck by-product formation compared to
the desirable arylation product.
6 Summary
A long-standing challenge in asymmetric catalysis is the discovery and development
of a suitable chiral catalyst. There are no fixed rules or paths to follow when it comes
to designing new catalysts. With the increasingly multidisciplinary nature of studies,
much progress has been achieved around asymmetric catalysis. We have highlighted
one approach in particular, the use of quantitative model to predict selectivity
(QSSR) with an outline of the workflow of the approach. A challenge in pursuing
QSSR approaches is the creation of a quantitative model from numerous possible
parameters. A ‘Goldilocks’ zone for a QSSR model is where the model is complex
enough to allow for useful predictions yet simple enough to allow for
physiochemical interpretations.
Synthetic chemists who are invested in experimental work may find this approach
helpful in terms of increasing the amount of useful information from hard-earned
experimental results. There are pros and cons for using different tools to aid ligand
discovery. The bottleneck of this approach is the time taken to synthesize the ligands
and test them. This approach may not always result in a faster process yet but
certainly offers a structured and systematic way to develop new chiral ligands.
References
1. Barron LD (2008) Chirality and life. In: Botta O, Bada JL, Gomez-Elvira J et al (eds)
Strategies of life detection. Springer, Boston, pp 187–201
2. Eliel E, Wilen S, Mander L (1994) Stereochemistry of organic compounds. Wiley, New York
3. Gawley RE (2006) J Org Chem 71:2411–2416
4. Smith SW (2009) Toxicol Sci 110:4–30
5. Nicolaou KC, Pappo D, Tsang KY et al (2008) Angew Chem Int Ed 47:944–946
6. Brunel JM (2005) Chem Rev 105:857–898
7. Christmann M, Brase S (2007) Asymmetric synthesis: the essentials, 2nd, completely revised
edition. Wiley, New York
8. Trost BM (1995) Angew Chem Int Ed 34:259–281
186
R. Ardkhean et al.
catalyst. The P:H ratio was found to be positively correlated with the Sterimol B 5
parameter for the substituent at C-6 position (B5 6 ) and a more subtle negative
correlation with the Sterimol L parameter for the substituent at the C-4 position
(L 4 ) of the catalyst. Further experiments showed that the phosphate catalyst can act
as a base to aid formation of by-product. Therefore, the QSSR supports the finding
that more sterically hindered phosphate slows down the formation of the by-product,
hence decreasing the kinetically competing Heck by-product formation compared to
the desirable arylation product.
6 Summary
A long-standing challenge in asymmetric catalysis is the discovery and development
of a suitable chiral catalyst. There are no fixed rules or paths to follow when it comes
to designing new catalysts. With the increasingly multidisciplinary nature of studies,
much progress has been achieved around asymmetric catalysis. We have highlighted
one approach in particular, the use of quantitative model to predict selectivity
(QSSR) with an outline of the workflow of the approach. A challenge in pursuing
QSSR approaches is the creation of a quantitative model from numerous possible
parameters. A ‘Goldilocks’ zone for a QSSR model is where the model is complex
enough to allow for useful predictions yet simple enough to allow for
physiochemical interpretations.
Synthetic chemists who are invested in experimental work may find this approach
helpful in terms of increasing the amount of useful information from hard-earned
experimental results. There are pros and cons for using different tools to aid ligand
discovery. The bottleneck of this approach is the time taken to synthesize the ligands
and test them. This approach may not always result in a faster process yet but
certainly offers a structured and systematic way to develop new chiral ligands.
References
1. Barron LD (2008) Chirality and life. In: Botta O, Bada JL, Gomez-Elvira J et al (eds)
Strategies of life detection. Springer, Boston, pp 187–201
2. Eliel E, Wilen S, Mander L (1994) Stereochemistry of organic compounds. Wiley, New York
3. Gawley RE (2006) J Org Chem 71:2411–2416
4. Smith SW (2009) Toxicol Sci 110:4–30
5. Nicolaou KC, Pappo D, Tsang KY et al (2008) Angew Chem Int Ed 47:944–946
6. Brunel JM (2005) Chem Rev 105:857–898
7. Christmann M, Brase S (2007) Asymmetric synthesis: the essentials, 2nd, completely revised
edition. Wiley, New York
8. Trost BM (1995) Angew Chem Int Ed 34:259–281
186
R. Ardkhean et al.