The Chiral Switch of Metolachlor: The Development of a Large-Scale Enantioselective Catalytic Process

The development of an enantioselective catalytic process for the technical preparation of chiral agrochemicals is illustrated by the case history of the herbicide (S)-metolachlor (trade name Dual Magnum®). Four synthetic routes were investigated in some detail. The key step for the technical process of the enantiomerically enriched compound is the asymmetric hydrogenation of an imine intermediate made possible by a new iridium ferrocenyl diphosphine catalyst system. Using optimized conditions, the isolated imine can be hydrogenated at a hydrogen pressure of 80 bar and 50°C with a substrate-to-catalyst ratio of >1'000'000. Complete conversion is reached within 4 h with an enantioselectivity of 79% with an initial turnover frequency (tof) exceeding 1'800'000 h-1. This sets a new standard for the technical application of enantioselective catalysts. Important aspects and results for the different phases of the process development of the catalyst system as well as minimal prerequisites for the use of enantioselective catalysts for the production of agrochemicals are discussed

Meniscal Repair Outcome in 3829 Patients With a Minimum Follow-up From 2 Years Up to 5 Years : A Meta-analysis on the Overall Failure Rate and Factors Influencing Failure

Background: The importance of meniscal repair is widely accepted because of the association of loss of meniscal tissue with the development of early-onset knee arthritis. Many factors influencing the results of meniscal repair have been reported, but results remain controversial. Purpose: This meta-analysis determines the pooled meniscal repair failure rate of studies with a minimum follow-up of 2 years up to 5 years, with a mean follow-up of 43 months. Moreover, selected failure-influencing factors are analyzed. Study design: Systematic review and meta-analysis; Level of evidence, 4. Methods: PubMed and Scopus were searched for studies published between January 2000 and November 2021 reporting on meniscal repair outcome with a minimum follow-up of 24 months. The overall pooled failure rate and pooled failure rates for possible predictors were calculated. Random-effect models were used to pool failure rates, and effect estimates in the form of odds ratios with 95% CIs were established. Results: The initial literature search identified 6519 studies. A total of 51 studies met the inclusion criteria. In total, 3931 menisci were included with an overall failure rate of 14.8%. Subgroup analysis revealed a significantly lower failure rate for meniscal repair with concomitant anterior cruciate ligament (ACL) reconstruction compared with knees without any reported injury to the ACL (8.5% vs 14%;P= .043). The pooled failure rate for lateral meniscal repair was significantly lower than that for medial meniscal repair (6.1% vs 10.8%;P= .031). Pooled failure rates of all-inside and inside-out repair were not significantly different (11.9% vs 10.6%;P&gt; .05). Conclusion: This meta-analysis on close to 4000 patients demonstrates an overall meniscal repair failure rate of 14.8% at a minimum follow-up from 2 years up to 5 years. Meniscal repair remains a procedure with a high failure rate, especially within the first 2 postoperative years. This review and meta-analysis also identified clinically relevant factors associated with favorable outcomes such as concomitant ACL reconstruction or repair of the lateral meniscus. All-inside meniscal repair with the latest-generation devices yields failure rates of &lt;10%. The failure mechanism and the time of failure is poorly documented; further studies are needed for a better understanding of the retear mechanism.</p