An overview of the most commonly used guanidine organocatalysts and their applications in organic synthesis is presented. Privileged structures of open, monocyclic and bicyclic guanidines and guanidinium salts are showcased with prominent examples from the literature. Free guanidines have found widespread use as strong Brønsted base catalysts in asymmetric synthesis. Guanidinium salts are employed as weak Brønsted acids or hydrogen-bond-donor catalysts and chiral counterions. The nucleophilic and Lewis basic properties of guanidines are still rarely exploited, but, as of late, have been gaining increasing recognition. 1 Introduction 2 Brønsted Base Catalysis 3 Hydrogen-Bond-Donor and Brønsted Acid Catalysis 4 Lewis Base Catalysis 5 Lewis Acid Catalysis 6 Conclusion

N-Protected o-aminobenzaldehydes smoothly react with α,γ-dialkylallenoates under Brønsted basic conditions to yield 2,3-disubstituted quinolines. This three-step reaction cascade of Michael addition, aldol condensation, and 1,3-N → C rearrangement uses the complete protecting group as a building block in a highly efficient C,C-bond formation of a new all-carbon quaternary center. Carbamate protected substrates (N-Boc, N-Cbz, N-Alloc) thus give 2-quinolin-2-yl-malonates, while amide protected substrates (N-Ac, N-Bz) afford 2-quinolin-2-yl-β-ketoesters in high yields.

Enantioselective [2 + 2]-photocycloaddition reactions on 4-(2'-aminoethyl)quinolones in solution were studied using the enantiomerically pure complexing agent 1 as source of chirality. The intermolecular reactions of fully N-protected substrates 5a-5c with different 2-alkyl-substituted acrylates 12-15 represent the first systematic study on the diastereoselectivity of their intermolecular [2 + 2]-photocycloadditions to unsymmetrically 1,1-disubstituted olefins (75-91% yield, d.r. = 58/42-95/5). N-Benzylic-protected photoproducts exo-16a/b-19a/b could easily be converted into lactams 20a/b-23a/b by a sequence of Boc deprotection and thermal lactamization (74-98% yield). Identical products 20a-22a were directly accessible by the intramolecular [2 + 2]-photocycloaddition of acrylic acid amides 2-4 (41-61% yield). The suitability of both pathways for an enantioselective reaction variant was proven (70-92% ee). Thus, tetracyclic lactams possessing the carbon framework C were obtained with good yields and enantioselectivities of up to 92% ee in intramolecular reactions. Comparative investigation of both routes showed that quinolone dimerization was the single most decisive factor preventing a complete chirality transfer. Functional group manipulations were successfully conducted with the primary photoproduct exo-17a. Finally, a new and unexpected type of benzylic hydrogen abstraction-radical cyclization reaction was discovered for substrate 5a, which explains the photochemical instability of substrates 2-5 under short wavelength irradiation (lambda = 300 nm).

Enantioselective synthesis in a new light: The template‐controlled [2+2] photocycloaddition leading to product 1 is the first example of this type of reaction in natural product synthesis. In addition, a retro‐benzilic acid rearrangement (→2), a Claisen rearrangement (→3), and a ring‐closing metathesis played decisive roles in the synthesis of the alkaloid (+)‐meloscine (4).

Cysteine plays a number of important functional and structural roles in Nature, often in the realm of catalysis. Herein, we present an example of a cysteine-catalyzed Rauhut-Currier reaction for a potentially biomimetic synthesis of Sch-642305 and related analogs. In this key step of the synthesis we discuss interesting new discoveries and the importance of substrate-catalyst recognition, as well as cysteine’s structural features. Also, we investigate the activity of Sch-642305 and four analogs in HIV-infected T-cells.