SummaryThe syntheses of palmitic acids and a nonadecane are reported with CF2 groups located 1,3 or 1,4 to each other along the aliphatic chain. Specifically 8,8,10,10- and 8,8,11,11-tetrafluorohexadecanoic acids (6b and 6c) are prepared as well as the singly modified analogue 8,8-difluorohexadecanoic acid (6a). Also 8,8,11,11-tetrafluorononadecane (27) is prepared as a pure hydrocarbon containing a 1,4-di-CF2 motif. The modified palmitic acids are characterized by differential scanning calorimetry (DSC) to determine melting points and phase behaviour relative to palmitic acid (62.5 °C). It emerges that 6c, with the CF2 groups placed 1,4- to each other, has a significantly higher melting point (89.9 °C) when compared to the other analogues and palmitic acid itself. It is a crystalline compound and the structure reveals an extended anti-zig-zag chain. Similarly 8,8,11,11-tetrafluorononadecane (27) adopts an extended anti-zig-zag structure. This is rationalized by dipolar relaxation between the two CF2 groups placed 1,4 to each other in the extended anti-zig-zag chain and suggests a design modification for long chain aliphatics which can introduce conformational stability.

Molecular iodine (10 mol%) efficiently catalyzes the ring expansion of 4-oxoazetidine-2-carbA C H T U N G T R E N N U N G aldehydes in the presence of tert-butyldimethylsilyl cyanide, or allylic and propargylic trimethylsilanes to afford protected 5-functionalized-3,4-dihydroxypyrrolidin-2-ones with good yield and high diastereoselectivity, through a C3 À C4 bond cleavage of the b-lactam nucleus. Interestingly, in contrast to the iodine-catalyzed reactions of 3-alkoxy-b-lactam aldehydes which lead to the corresponding g-lactam derivatives (rearrangement adducts), the reactions of 3-aryloxy-b-lactam aldehydes under similar conditions gave b-lactam-fused chromanes (cyclization adducts) as the sole products, through exclusive electrophilic aromatic substitution involving the C3 aromatic ring and the carbaldehyde. In order to support the mechanistic proposals, theoretical studies have been performed.

Abstract:The difluoromethylene (CF2) group has a strong tendency to adopt corner over edge locations in aliphatic macrocycles. In this study, the CF2 group has been introduced into musk relevant macrocyclic ketones. Nine civetone and five muscone analogues have been prepared by synthesis for structural and odour comparison. X-Ray studies indeed show that the CF2 groups influence ring structure and they give some insight into the preferred ring conformations, triggering a musk odour as determined in a professional perfumery environment. The historical conformational model of Bersuker et al. for musk fragrance generally holds, and structures that become distorted from this consensus, by the particular placement of the CF2 groups, lose their musk fragrance and become less pleasant.

β‐Lactam–oxindole hybrids have been synthesized in good yields in a one‐pot procedure through efficient and stereoselective capture of an oxonium ylide with azetidine‐2,3‐diones. The reaction allows high to moderate control of stereoselectivity, depending on the 3‐diazo‐oxindole precursor and the hydroxylic compound used. Two new quaternary stereogenic centers were formed; the stereochemistry at the C‐3 quaternary center was controlled by a bulky substituent at C‐4, whereas the stereoselectivity in the adjacent second quaternary stereogenic center was controlled by the α‐diazo‐oxindole. The stereochemistry of both quaternary centers has been unambiguously assigned by single‐crystal X‐ray diffraction.

Passerini (P-3CR) and Ugi (U-4CR) reactions were investigated in 4-oxoazetidine-2-carboxaldehydes, affording the corresponding Passerini and Ugi adducts with moderate diastereoselectivity in high yields. Fortunately, the obtained mixtures of isomers syn/anti were separated in most cases. The scope of both IMCRs has been studied using a variety of isocyanides, carboxylic acids and amines. Ugi adducts were used for the preparation of unusual 2-azetidinones fused to medium-sized rings via RCM. In addition, β-lactam-diketopiperazine hybrids have also been prepared from the corresponding Ugi adducts.

Passerini (P-3CR) and Passerini−Smiles reactions were investigated in azetidine-2,3-diones, affording the corresponding 3,3-disubstituted-β-lactams with complete diastereoselectivity in high yields. The study has been carried out using different isocyanides, carboxylic acids, and phenols showing the scope of both reactions. In addition, the regioselective synthesis of highly functionalized β-lactam-triazole hybrids has been developed via a Passerini/CuAAC sequence. Interestingly, the use of dialkynes/diazides or trialkynes/triazides as linkers in the CuAAC step has allowed the synthesis of C 2 and C 3 symmetric βlactam-triazole hybrids, respectively.

The organocatalyzed U-3CR of 4-oxoazetidine-2-carbaldehydes has been studied. In addition, the organocatalyzed P-3CR of 4-oxoazetidine-2-carbaldehydes and azetidine-2,3-diones has been described for the first time. U-3CR and P-3CR adducts have been obtained in good yields and reasonable diastereoselectivities. Phenyl phosphinic acid has been the catalyst of choice to study the scope of both organocatalyzed multicomponent reactions using a variety of β-lactams, isocyanides, and amines. Highly functionalized U-3CR and P-3CR adducts derived from β-lactams have proved to be useful substrates for the preparation of enantiopure γ-lactams and γ-lactones via N1-C2 β-lactam ring opening/cyclization under acidic or basic conditions.

A series of five 12-dodecanolides have been synthesised containing CF 2 groups at C5, C6, C7, C8 and in one case a double substitution at C5 & C8, as a strategy to bias the conformational space accessed by these macrocycles, and to assess if the analogues may act as mimetics for 12-decenolide pheromones associated with the Emerald Ash Borer.