Abstract. The influence of protecting the hydroxyl group of a b-oxy-a-diazo carbonyl compound on the competi- tion between the Wol rearrangement (WR) and the [1,2]- hydrogen shift (HS) was investigated theoretically. Stationary points on the potential-energy surface were located with the B3LYP density functional and the 6- 31G** basis set. For the basic system geometry optimi- sations at B3LYP/6-311+G** were performed to validate the reliability of the B3LYP/6-31G** calculations. Single- point energy calculations were carried out at the B3LYP/ 6-311+G** level on the B3LYP/6-31G**-optimised ge- ometries. Further insight into the processes was achieved with the aid of the theory of ‘‘atoms in molecules’’ of Bader. The calculated energy barriers qualitatively pre- dicted the yields of HS and WR obtained experimentally. In order to rationalise the calculated energy barriers, it was necessary to take into account not only the electro- negativity of the protective groups but also the alignment of the migrating groups with the depletion sites at the carbene centre. Further, when the hydroxyl group was not protected the existence of an intramolecular hydrogen bond played an important role in both HS and WR. Key words: Wol rearrangement – [1,2]-hydrogen shift – b-Oxy-a-diazo carbonyl compounds – Density functional theory calculation – Laplacian distribution of the charge density 1 Introduction Rearrangement reactions of nitrogen, oxygen or carbon play an important role in chemistry. Among them the [1,2]-carbon and hydrogen shifts (HS) are of great importance and interest in organic synthesis and photo- chemistry [1–19]. Particularly, the isomerisation reac- tions of ketocarbenes are presently the subject of extensive studies [20–35]. Lo´pez-Herrera and Sarabia [36, 37] departing from D-glyceraldehyde have recently designed a route aimed at synthesising 1-methyl-2- hydroxy synthons on asymmetric carbons, which con- stitute the skeleton of some antibiotic macrolides. The synthesis utilised the wol rearrangement (WR) (Scheme 1) of a-ketodiazo compounds as its principal reaction step. The photolytical cleavage of the diazo compound presumably created a ketocarbene species, which rear- ranged (by migration of the methyl group at C 2 towards the carbene centre, C 4 ) to yield a ketene, which in turn reacted with methanol to give the ester. However, the product was not the ester but a b-diketone as a consequence of the shift of the hydrogen atom linked to C 5 (H 8 ). Moreover, the 100% yield indicated clearly its absolute predominance. Some strategies were ad- dressed to avoid this competitive reaction. First, they thought that protection of the hydroxyl group in the b position, especially with electron-withdrawing substitu- ents, could diminish the ability of hydrogen to undergo the transposition towards the carbene centre since it would be more strongly bonded to the adjacent carbon atom than before. In principle, the yields obtained supported that hypothesis (see Scheme 1 and Ref. [36]). We have already studied these processes as well as some alternative reaction channels on the AM1 potential energy surface (PES) [38]. Subsequent ab initio and density functional theory (DFT) (B3LYP) studies car- ried out on a model system have shown that a hydrogen- bond interaction could condition the prevalence of the [1,2]-HS over the WR [39]. In this paper we report a theoretical study of the competing HS and WR reactions of hydroxymethyl- Correspondence to: J.J. Quirante Regular article The influence of protecting the hydroxyl group of b-oxy-a-diazo carbonyl compounds in the competition between Wol rearrangement and [1,2]-hydrogen shift. Density functional theory study and topological analysis of the charge density S. Calvo-Losada 1 , T.L. Sordo 2 , F.J. Lo´pez-Herrera 3 , J.J. Quirante 1 1 Departamento de Quı´mica Fı´sica, Facultad de Ciencias, Campus de Teatinos s/n, E-29071 Ma´laga, Spain 2 Departamento de Quı´mica Fı´sica y Analı´tica, Facultad de Quı´mica, Julia´n Claverı´a s/n, E-33006, Oviedo, Asturias, Spain 3 Departamento de Bioquı´mica, Biologı´a Molecular y Quı´mica Orga´nica, Facultad de Ciencias, Campus de Teatinos s/n, E-29071, Ma´laga, Spain Received: 30 December 1998 / Accepted: 7 May 1999 / Published online: 4 October 1999 Theor Chem Acc (2000) 103:423–430 DOI 10.1007/s002149900062