The Total Synthesis of Chalcitrin. Biological & Biomedical Sciences Coursework

The Total Synthesis of Chalcitrin
J. Am. Chem. Soc. 2019, 141, 4515−4520
Assessment will be based on:
● the retrosynthesis
● the understanding of the details of the chemistry involved
● its organisation into a coherent form
● the clarity of review
● critique and discussion of the key steps and strategy in the synthesis
The aim is to discuss the critical features of the synthesis; the focus should be:
● the nature (mechanism, i.e. arrow-pushing!) of key C-C bond forming steps
● overall strategy
● stereocontrol 
● and any other novel/interesting components of the published work. 
Detailed chemistry of protection-deprotection sequences and redox chemistry need not be emphasised, but may be necessary in some cases 
Plan for review -- breakdown each scheme and analyse the chemistry for each step
Intro -- Patrick
● Source of Chalcitrin
● Pulvinic acid dimers (analogues of Chalcitrin)
● Interest area of group
● Overview of dimer scaffold
Scheme 1: Retrosynthesis [8 steps] 
● Show general reaction for coupling reaction (heck/stille) with possibilities of switching between the halide and metal partners -- shows great flexibility of the synthesis
Scheme 2: Formation of tricyclic intermediate [10 steps] 
● Preparing the tricyclic intermediate to be the metal (tin) coupling partnerScheme 3: First coupling attempt [6 steps]
● Stille and heck reactions coupled with pulvinic acid as the halide partner because this is the faster route (cannot directly convert pulvinic acid to stannane)
● Stille was determined to be the only successful coupling reaction, so now the target is to have tandem (2x) stille reaction instead of Stille+Heck
● This requires preparing a double vinyl halide intermediate for subsequent conversion to bistannane tricyclic partnerScheme 4: Preparing double vinyl halide intermediate [8 steps] Scheme 5: Second and third coupling attempts [4 steps]● Tandem stille reactions used as planned
● 2nd attempt - Bistannane tricyclic intermediate + halide pulvinic acid = no product
● Switch the partners; have the tricyclic be the halide partner. This is the flexibility of the reaction proving to be advantageous
● 3rd attempt - Double halide tricyclic intermediate + stannane pulvinic acid = productScheme 6: Preparing stannane pulvinic acid [6 Steps] 
Stannane group cannot be directly added/substituted to pulvinic acid commercial source● Therefore the group had to synthesise the stannane pulvinic acid from scratch (tetronic acid)Conclusion
● Overall yield, total steps
● Summarise and highlight some key reactions?
● Interesting bits:
○ In the end, the longest route (everything made from scratch) was the only successful path to product reported○ The flexibility of switching the possible coupling partn...