The combined regio- and stereo-controlled carbometalation reaction of alkynyl sulfoxide followed by a zinc homologation and finally an allylation reaction led, in a single-pot operation, to chiral homoallylic alcohols in excellent yields and diastereoselectivities for the creation of chiral quaternary and tertiary centers. The key features in all of the reactions that are described in this article are the high degree of stereocontrol, the level of predictability, and "the ease of execution" which ensures success in the application of such methods. The chiral sulfinyl moiety can be finally removed by simple treatment with alkyllithiums, which allows further functionalizations of the carbon skeleton. By using one of these methods, the creation of chiral quaternary centers with the smallest possible difference, namely CD3 versus CH3 and 13CH3 versus CH3, was easily performed.

Despite the advances in stereoselective carbonyl allylation reactions, the creation of quaternary stereocenters in the addition of 3,3'-disubstituted allylmetals to aldehydes is still a challenging issue. This feature article describes the most powerful approaches that have been devised to address this problem.

The one-pot preparation of chiral homoallylic alcohol and amine derivatives was easily achieved by carbocupration of alkynyl sulfoxides followed by an in situ zinc homologation and reaction with aldehydes or imines. In this process, three new carbon-carbon bonds were created as well as quaternary and tertiary chiral centers with excellent diastereo- and enantioselectivities.

Dedicated to Professor Miguel Yus on the occasion of his 60th birthdayThe design of new methods for the enantioselective construction of all-carbon quaternary stereogenic centers in acyclic systems is still a critical and challenging objective in modern chemistry.[1] Currently, the most-successful methods are asymmetric copper-catalyzed conjugate addition, [2] asymmetric Michael reactions, [3] asymmetric sigmatropic rearrangements, [4] and asymmetric electrophilic [5] and nucleophilic [6] allylic alkylation. However, the enantioselective formation of such all-carbon quaternary stereogenic centers by attack at the g carbon atom of nucleophilic allylic substrates (that is, the reaction of 3,3-disubstituted allyl metal species with electrophiles) is much less frequent. [7] In this context, we reported an efficient multicomponent reaction for the diastereoselective formation of quaternary centers (Scheme 1).[8]The key features of this reaction are the high degree of stereoselectivity and predictability, and the ease of execution. The reaction requires the in situ combination of a stereoselective carbometalation (introduction of the R 2 substituent), a zinc homologation (introduction of the CH 2 unit of the allyl zinc fragment), [9] and intramolecular chelation of the zinc atom by the sulfoxide, which results in the very high diastereoselectivity observed in the reaction of the allyl zinc reagent with various aldehydes.[8] The presence of the sulfoxide is essential to slow down the equilibration process of the allylic organometallic species 1 (through intramolecular chelation to the zinc atom) but also as a source of chirality and as a regiocontrol element for the carbometalation reaction. When the same reaction was performed with the nonfunctionalized 1-hexyne 2, the expected homoallylic alcohol 3 was obtained in good yield but as a 1:1 mixture of two diastereoisomers (Scheme 2). In such cases, the homologation reaction of the vinyl copper species with the zinc carbenoid leads to an allyl zinc species, such as 4, which is not configurationally stable, [10] and the two geometrical isomers that result from its metallotropic equilibrium react with the aldehyde.To further extend our new approach to the creation of allcarbon quaternary stereocenters, we were interested in finding an alternative method, not based on intramolecular chelation of the substrate but rather on intermolecular chelation by an external ligand, to slow down the metallotropic equilibrium. We chose to focus on enantiomerically pure R-configured Ellman N-(tert-butylsulfinyl)imines 5 as chiral ligands.[11] We were interested in the potential of sulfinylimines, which can be used as chiral nitrogen-containing intermediates for the preparation of a wide range of chiral amines, for the intermolecular stabilization of the allyl zinc species. [12] In our first approach (Scheme 3), the disubstituted vinyl iodides 6 a-c, which were prepared readily by the carbocupration of 1-octyne, [13] were treated with tBuLi in THF at À78 8C followed by CuI (1 equiv). The...

[structure: see text]. Stereochemically pure polysubstituted vinyl sulfoximines and sulfones are easily prepared by a copper-catalyzed syn carbozincation reaction of the corresponding alkynyl derivatives.