Acyl fluorides amides

H-Bond Acceptor (HBA) Acyl chlorides Acyl fluorides Hetero nitrogen aromatics Hetero oj gen aromatics Tertiary amides Tertiary amines Other nitriles Other nitros Isocyanates Peroxides Aldehydes Anhydrides Cyclo ketones Ahphatic ketones Esters Ethers Aromatic esters Aromatic nitriles Aromatic ethers Sulfones Sulfolanes... 

Many aldehydes and ketones have been converted to g m-difluoro compounds with sulfur tetrafluoride (SF4), " including quinones, which give 1,1,4,4-tetra-fluorocyclohexadiene derivatives. With ketones, yields can be raised and the reaction temperature lowered, by the addition of anhydrous HF. Carboxylic acids, acyl chlorides, and amides react with SF4 to give 1,1,1-trifluorides. In these cases the first product is the acyl fluoride, which then undergoes the ge i-difluorination reaction ... 

Deoxo-Fluor reagent is a versatile reagent for acyl fluoride generation and subsequent one-flask amide coupling. Georg and coworkers have explored the utility of this reagent for the one-flask conversion of acids to hydroxamic acids and Weinreb amides (Scheme 105) ". ... 

The elimination of carbonyl difluoride from trifluoromethylated acyl fluorides is catalysed by amides. For example, dmf induced the following transformation at 130 "C [1545] ... 

Acyl fluorides. Carboxylic acids are readily transformed into acid fluorides by this reagent in the presence of i-Pr2NEt. Weinreb amides can be prepared henceforth. W-Protected chiral a-amino acids are derivatized without racemization. 

When differences in hybridization are removed, the relative trends in the donor ability of lone pairs correlate well with the electronegativity of heteroatoms. In a textbook example, reactivity of carboxylic acid derivatives increases in the following order amide < ester < acyl fluoride due to decrease in n,j interaction (X=N>0>F). Lower importance of negative conjugation leads to increased positive charge and electrophi-licity of the carbonyl carbon (see Chapter 6 for further discussion). 

Acetylenedicarbonyl fluoride reacts with alcohols and amines to furnish esters and amides, respectively. On the other hand, ethanethiol adds to the triple bond of the substrate despite the extremely high reactivity of the acyl fluoride carbonyl (62). Aromatic amines undergo both Michael addition and amida-tion (63). 

N-Formylsaccharin 102, an easily accessible crystalline compound, has been employed as an efficient CO source in Pd-catalyzed fluorocarbonyl-ation of aryl halides 103 to afford the corresponding acyl fluorides 104 (13OL5370). Reagent KF is expected to serve as a dual role not only as a nucleophile for Pd-catalyzed carbonylation but also as an activator for CO generation from 102. The reactions use a near-stoichiometric amount of the CO source (1.2 eq) and tolerate diverse functional groups. The acyl fluorides 104 can be readily transformed into various carboxylic acid derivatives such as carboxylic acid, esters, thioesters, and amides in a one-pot procedure. 

A typical preparation protocol is shown in Scheme 2.146. In the first step in a one-pot reaction, 2,2 -[(l ,l )-hydrazine-l,2-diylidenebis(methanylylidene)] dibenzoic acid is reacted with 1,2-diphosphinobenzene and succinyl chloride to create the racemic bisdiazaphospholane with moderate yield. After condensation of all four carboxylic groups with an optically pure amine, diastereomeric amides are formed, which can be finally separated by liquid chromatography. By using phthaloyl chloride in the cyclization step or other enantiopure aryl amines, several analogs are accessible. For the linkage of sterically encumbering or less nucleophilic amines, the route via the corresponding acyl fluorides proved to be more successful [65]. 

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